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DISCUSSION | satiety, weight loss, aortic stiffness | In the current study we aimed to see how an acute 3‐day very low‐calorie CR diet might affect body weight/ composition, metabolism, cardiovascular health, and circulating metabolic factors which may explain changes in these parameters in Ow and Ob men and women. Three days of CR resulted in significant weight loss, loss of total body fat/visceral fat, and loss in waist and hip circumference, without significant changes in body water or muscle mass. These anthropometric changes might be supported by switching from reliance on carbohydrates to oxidizing more fat as fuel, which could explain, along with increased circulating leptin, the loss of fat mass. There were minimal changes in blood pressure and blood lipids/glucose, suggesting nominal effects, although augmentation pressure and index, indicators of aortic stiffness responded favorably to the intervention. In terms of individual perceptions of the effects of short‐term CR on hunger or fullness, there was not much effect, other than satiety which peaked on Day 2 of the diet. Self‐reported sleep latency and duration were also unaffected. Collectively, the findings from the current study suggest that 3 days of CR acutely induces weight and fat loss, increases circulating leptin and resting fat oxidation, without much change to cardiovascular health, feelings of hunger, or sleep in adult men and women who are Ow or Ob. Considering these findings, such a short‐term very low‐calorie CR diet could be an effective way to induce the onset of weight loss, or be incorporated as part of a long‐term intermittent fasting diet approach to weight loss, but further studies are warranted to determine efficacy in an IF model. | PMC10659943 | |
Impact of | weight loss | COMPLICATIONS | Caloric restriction is not a novel approach of losing weight, in those that desire to do so, and has even been purported to induce health benefits beyond weight loss (Fontana et al., This 3‐day CR diet may be a way to commence an individual's weight loss in a distinct but effective way, but perhaps more importantly could be part of an intermittent CR or intermittent fasting dietary approach to weight loss and body composition improvement. Consumers without knowledge or training may struggle to identify adequate dietary approaches to weight loss, such as IF, and the dietary planning associated with them, therefore an “off the self” product or suite of products could make adopting such a weight loss strategy easier. Thus, findings from the current study may provide insight into a new paradigm of IF (4:3, 4 days ad libitum, 3 days caloric restriction using the 3‐day diet) and provide evidence on an “off the shelf” way of carrying out a version of IF, as many individuals may struggle to plan and effectively carry out such dietary interventions. Such an IF approach might avoid complications associated with chronic/continuous CR (Dirks & Leeuwenburgh, | PMC10659943 |
Impact of | reductions in blood pressure | Long‐term caloric restriction has been demonstrated to induce favorable cardiovascular effects, namely reductions in blood pressure and improved lipid profile (Fontana et al., Although, in the present study, using a short‐term 3‐day CR down to 590 kcal/d of intake we observed no significant changes in systolic, diastolic, or mean arterial blood pressure measured peripherally or estimated centrally at the aorta (Figure In terms of lipid profile, while longer term CR may induce reductions in total cholesterol, LDL cholesterol, triglycerides, and glucose with concomitant increases in HDL cholesterol, thereby improving the total/HDL ratio (Jakobsdottir et al., | PMC10659943 | |
Impact of | Obesity, metabolic inflexibility | OBESITY | Obesity is associated with impaired ability to use fat or metabolic inflexibility (Kelley et al., | PMC10659943 |
Impact of | satiety, fullness, Anton | There is less known about the effects of acute or short‐term CR on perceptions hunger/desire to eat or satiety/fullness, although longer term CR is known to induce psychological predilection to hunger and less so to feelings of satiety or fullness (Anton et al., | PMC10659943 | |
Limitations | Dietch & Taylor, | SECONDARY | The present study, as with every study, was not conducted without limitations. As a secondary or tertiary outcome, in assessing sleep we opted for a less invasive option to minimize participant burden, which does relate significantly to sleep duration, even if perhaps imperfectly (Dietch & Taylor, | PMC10659943 |
CONCLUSION | weight loss | In summary, the findings from the current study highlight that 3 days of a novel standardized very low‐calorie diet CR (ca. 590 kcal/d intake) induces significant weight and fat loss, increases circulating leptin, increases fat oxidation, without much change to blood lipid profile, blood pressure, feelings of hunger, or sleep in adult men and women who are Ow or Ob. These novel findings suggest that such a diet could be beneficial as an approach to initiating weight loss in those that are Ow or Ob, or could be utilized in an intermittent fasting diet (e.g., alternate day or 5:2) approach to weight loss, but further studies are warranted to determine efficacy and whether such weight loss is sustained. | PMC10659943 | |
AUTHOR CONTRIBUTIONS | Conceptualization, JD and SI; methodology, JD and SI.; formal analysis, AC, BY, JD, SI.; investigation, JD, AC, BY, CK, AC, SI.; resources, SI AC; data curation, AC, BY, JD, SI.; writing—original draft preparation, JD, SI, CK; writing—review and editing, JD, SI, AC, BY CK AC.; visualization, AC BY SI; supervision, SI JD; project administration, SI.; funding acquisition, SI. All authors have read and agreed to the published version of the manuscript. | PMC10659943 | ||
FUNDING INFORMATION | This research was funded by Plexus Worldwide, grant number 2204‐1028. | PMC10659943 | ||
DISCLOSURES | Plexus Worldwide provided funding and product for the current study although the funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. | PMC10659943 | ||
ETHICS STATEMENT | All participants provided written informed consent prior to participation. This study was reviewed and approved by the Institutional Review Board at Skidmore College (#2204‐1028) and registered with clinicaltrials.gov (NCT05422391). This study was carried out in accordance with the principles set forth in the most recent revisions to the Declaration of Helsinki. | PMC10659943 | ||
Supporting information |
Table S1.
Click here for additional data file.
Table S2.
Click here for additional data file. | PMC10659943 | ||
ACKNOWLEDGMENTS | The authors would like to thank the participants for volunteering and completing the study. We would also like to thank the health services nursing team at Skidmore for their assistance in completing the study. | PMC10659943 | ||
DATA AVAILABILITY STATEMENT | The data are available upon reasonable request by the corresponding author. | PMC10659943 | ||
REFERENCES | PMC10659943 | |||
1. Introduction | oxidant damage | SKIN | These authors contributed equally to this work.Preliminary findings from multiple studies indicate that dietary intake of soy-derived isoflavones exert beneficial effects on the skin including defense against oxidant damage, stimulation of collagen synthesis, and increased hydration. This study aims to investigate how oral supplementation of a soy protein isolate with added isoflavones (SPII) affects components of photoaging such as facial wrinkles and dyspigmentation, and skin biophysical measures such as skin hydration and sebum excretion in postmenopausal women. This 6-month prospective, randomized double-blind controlled study was conducted on 44 postmenopausal women with Fitzpatrick skin types I, II, and III who were randomized to receive either casein protein or SPII. A high-resolution facial photography system was used to measure wrinkle severity and pigmentation at 0, 8, 16, and 24 weeks. Skin biophysical measurements included skin hydration and sebum production. The average wrinkle severity was decreased in the SPII intervention group at week 16 and week 24 by 5.9% and 7.1%, respectively, compared to the baseline. Compared to the casein group, average wrinkle severity was significantly decreased at week 16 (Plant-derived isoflavones are naturally occurring nonsteroidal compounds that resemble estrogens and are commonly classified as phytoestrogens [The main dietary sources of isoflavones for humans are soybean and soy-derived products, which primarily contain daidzein and genistein [Isoflavones may modulate women’s health through multiple modalities. Supplementation has been shown to mitigate multiple symptoms of perimenopausal and postmenopausal women [Postmenopausal women are more susceptible to facial aging due to a shift in hormonal balance and decrease in collagen synthesis [Food-based interventions have previously demonstrated modulatory effects on skin aging [Foods rich in antioxidants such as vitamin E (alpha-tocopherol) have also been implicated in facial wrinkles and pigmentation. Almonds are one example of a food that contains alpha-tocopherol. Two studies demonstrated that daily consumption of almonds in postmenopausal women with Fitzpatrick skin types 1–3 for either 16 or 24 weeks resulted in a significant decrease in wrinkle severity and facial pigment intensity [Soy isoflavones have garnered interest for a range of functions including their antioxidant, phytoestrogenic, and anti-inflammatory properties [As a result of these findings with soy isoflavones and soy protein, there has been growing interest to assess the intake and supplementation of soy-based products for skin health. A previous study assessing postmenopausal women with Fitzpatrick skin types 1–3 who were supplemented with a mixture of soy isoflavones, lycopene, vitamin C, vitamin E, and fish oil for 14 weeks showed a reduction in wrinkle depth [The current study builds on all of these preliminary studies to comparatively study soy protein containing isoflavones (SPII) against a calorie-matched casein protein without added isoflavones. Specifically, this study investigates how supplementation with SPII shifts skin health including the appearances of wrinkles and pigmentation as well as skin biomechanical properties such as hydration and sebum production. | PMC10574417 |
2. Methods and Materials | PMC10574417 | |||
2.1. Materials | The SPII used in this study was provided by Dupont (Wilmington, DE, USA) and contained the following ingredients: soy protein (isolated soy protein with less than 2% lecithin), sugar, fructose, resistant maltodextrin, spray-dried corn oil shortening (corn oil, corn syrup solids, sodium caseinate, and BHT and propyl gallate (to help protect flavor)), natural and artificial flavor, xanthan gum, salt, vitamin/mineral (sodium ascorbate, maltodextrin, vitamin E, ferric orthophosphate, niacin, calcium pantothenate, zinc oxide, manganese sulfate, pyridoxine hydrochloride, riboflavin, thiamin, vitamin A, chromium chloride, folic acid, biotin, potassium iodide, sodium molybdate, sodium selenite, vitamin K, vitamin D, and vitamin B12), sucralose, acesulfame k, and powder. The total caloric content for 46 g of the powdered SPII product was 170 calories, with a breakdown of 2 g of total fat (3% of daily value), 550 mg of sodium (24% of daily value), 10 g of total carbohydrates (4% of daily value), 3 g of added sugars (6% of daily value), and 30 g of protein.The casein protein powder that served as a control consisted of the following: sodium caseinate, sugar, fructose, resistant maltodextrin, spray dried corn oil shortening (corn oil, corn syrup solids, sodium caseinate, and BHT and propyl gallate (to help protect flavor)), natural and artificial flavor, xanthan gum, salt, vitamin/mineral (sodium ascorbate, maltodextrin, vitamin E, ferrice orthophosphate, niacin, calcium pantothenate, zinc oxide, manganese sulfate, pyridoxine hydrochloride, riboflavin, thiamin, vitamin A, chromium chloride, folic acid, biotin, potassium iodide, sodium molybdate, sodium selenite, vitamin K, vitamin D, and vitamin B12.), sucralose, acesulfame k, and powder. The total caloric content for 45 g of this powered casein powder was 170 calories, with a breakdown of 1.5 g of total fat (2% of daily value), 430 mg of sodium (19% of daily value), 10 g of total carbohydrates (4% of daily value), 3 g of added sugars (6% of daily value), and 30 g of protein. | PMC10574417 | ||
2.2. Study Design, Recruitment, and Randomization | SKIN, RECRUITMENT | This prospective, double-blind, randomized controlled trial was conducted in the greater Sacramento area at Integrative Skin Science and Research (Sacramento, CA, USA). Methods of recruitment included local dermatology clinics and social media advertising. The study protocol and consent were reviewed and approved by the Allendale Institutional Review Board (Protocol ID: SYW_01) and registered at In total, 135 individuals were assessed for eligibility and 44 participants were randomized to either SPII or casein. A CONSORT diagram is presented in | PMC10574417 | |
2.3. Inclusion and Exclusion Criteria | Healthy postmenopausal women aged 50 to 70 were eligible to participate if they were Fitzpatrick skin types I, II, or III and had a BMI between 18.5 and 35 kg/m | PMC10574417 | ||
2.4. Facial Imaging and Skin Biophysical Measurements | The BTBP 3D Clarity Pro | PMC10574417 | ||
2.5. Statistical Analysis | The primary endpoint of this study was to assess whether SPII supplementation could decrease wrinkle severity and pigment intensity compared to the casein group after 24 weeks. Secondary endpoints included assessments of skin hydration and sebum excretion within groups. The data were analyzed at 0, 8, 16, and 24 weeks. Statistical comparisons were made by using a Student’s | PMC10574417 | ||
3. Results | Out of 135 participants who were screened, 44 postmenopausal females met the enrollment criteria and were randomized into the SPII (n = 23) or the casein group (n = 21). The mean (SD) age for participants in SPII and casein groups was 62 ± 6 y and 64 ± 4 y, respectively. | PMC10574417 | ||
3.1. Imaging System-Based Photographic Analysis of Wrinkle Severity and Pigment Intensity | The average wrinkle severity in the SPII group decreased by 5.9% and 7.1% at week 16 and 24, respectively. Wrinkle severity was decreased in the SPII group compared to the casein protein group at week 16 ( | PMC10574417 | ||
3.2. Skin Hydration | SKIN | Skin hydration was significantly increased in the soy protein intervention group by 39% in the left cheek and 68% in the right cheek at week 24 ( | PMC10574417 | |
3.3. Sebum Excretion | Compared to baseline, there were no significant changes in sebum production in either group at any time point ( | PMC10574417 | ||
3.4. Facial Photography | High-resolution photography was taken for both groups at baseline and week 8, 16, and 24 ( | PMC10574417 | ||
3.5. Adverse Events | constipation | There was one episode of constipation that led to withdrawal in the casein group. | PMC10574417 | |
4. Discussion | Estrogen-deficient, malignant melanoma, hyperpigmentation, breast cancer, merkel cell carcinoma, hair loss, acne | MALIGNANT MELANOMA, HYPERPIGMENTATION, BREAST CANCER, MERKEL CELL CARCINOMA, HAIR LOSS, ACNE | In this 24-week, prospective, randomized controlled trial, 30 g/d of soy protein powder containing 50 mg of isoflavones daily showed significant improvements in wrinkle severity, pigmentation, and hydration at week 24. In addition to sun protective habits such as sunscreen use and sun protective clothing, the current results support the adjunctive use of soy-protein-derived isoflavones for the reduction in skin wrinkles and dyspigmentation such as occurs in skin photoaging. Our study supports the use of a soy-based protein supplement with isoflavones to improve signs of facial skin photoaging such as wrinkles and facial pigmentation in postmenopausal women with Fitzpatrick skin types 1–3. Compared to the casein protein group, the SPII group experienced a significant decrease in wrinkle severity at week 16 and 24, and significant decrease in average pigment intensity at week 24. The mechanism by which soy isoflavones mediate wrinkle severity and pigment intensity may be related to its antioxidative [The finding that SPII supplementation lead to an improvement in the facial pigmentation has support from the literature. Soy-based extracts have been shown to reduce facial hyperpigmentation when applied topically [The SPII group also experienced a significant increase in skin hydration at week 24 compared to baseline in both cheeks. Although this difference was not statistically significant, we chose to present the data as right and left cheeks rather than an overall average as there could be other confounders for variations in the cheeks such as driving-related sun exposure. For example, in the United States, where drivers experience increased ultraviolet (UV) exposure on the left side, malignant melanoma and merkel cell carcinoma were significantly more likely to occur on the left side of the face or arms [Estrogen-deficient skin, such as in postmenopausal women, is characterized by the loss of collagen, elastin, fibroblast function, and vascularity [Interestingly, neither intervention produced significant differences in sebum excretion. While the literature on the associations between soy and sebum production are lacking, one study found that the removal of precipitated casein in lactoferrin, a whey milk protein, led to decreased sebum production [As opposed to topical application, oral supplementation may have other benefits that could be considered an integrative and holistic approach to skin care. For example, soy protein supplementation may have an overall anti-inflammatory effect on the body with a reduction in the circulating IL-6 and TNF-alpha levels [Our findings reveal several potential follow-up studies that would be warranted. For example, future studies should evaluate the role of SPII on other aspects of women’s health that can range from hair loss to acne to vaginal support. The role of supplementation-derived isoflavones vs. food-derived isoflavones should be explored further as well.This study evaluated the use of soy protein containing 50 mg isoflavones and a previous study showed that consuming daily a soy extract containing 100 mg isoflavones improved epidermal thickness and increased collagen and elastin fibers in the dermis [Although some concerns have arisen about the safety of isoflavones, particularly about the impact of soy on women with breast cancer. However, the evidence supports the opposite. Increasing consumption of soy isoflavones was associated with lowered risk for breast cancer in both pre-menopausal and post-menopausal women [ | PMC10574417 |
Limitations | This study had numerous dietary restrictions that may not be fully representative of a person’s true diet outside of a clinical research setting. However, these restrictions also reduced potential confounding. This study had a relatively small sample size with all subjects being postmenopausal women, and the soy and casein were provided as protein powders that required the intake of large volumes of water on a daily basis and led to equal levels of withdrawals from each group. Nevertheless, our study was able to recruit enough participants to show statistically significant differences. Future studies should consider intervening with isoflavone-rich products that are less burdensome, such as traditional soy foods like tofu or isoflavone supplements. Future studies should also investigate how soy isoflavones in isolation may influence skin photoaging, whereas the SPII utilized in our study had a small proportion of added ingredients such as niacin and vitamin A, which may have contributed to dermatological effects of their own. This study was limited to Fitzpatrick skin types I, II, and III, and the results reported here cannot be generalized to all Fitzpatrick skin types. Similarly, because this study was limited to postmenopausal women, the results reported here cannot be extended to premenopausal or perimenopausal women. Because this study intervened with SPII with the active component of soy isoflavones, other isoflavone-rich soy foods such as tofu, soymilk, edamame, and tempeh may also exert similar benefits and should be the focus of future studies. | PMC10574417 | ||
5. Conclusions | SKIN PIGMENT | In conclusion, supplementation with a standardized, multicomponent soy protein isolate with added isoflavones may improve facial wrinkle severity, reduce skin pigment intensity, and increase skin hydration in postmenopausal women with Fitzpatrick skin types I, II, and III. Future studies assessing supplementation of a soy protein with added isoflavones with an expanded population including males, younger participants, and higher Fitzpatrick skin types are warranted. Additionally, studies utilizing isolated soy protein and isoflavones to assess its effects on skin health may strengthen these associations. Since phytoestrogens may mimic estrogenic effects in the skin, future studies might also investigate the systemic effects of soy isoflavones in postmenopausal women from a gynecological or multidisciplinary perspective. | PMC10574417 | |
Author Contributions | Conceptualization, R.K.S. and V.F.; Methodology, R.K.S., V.F. and J.M.; Formal Analysis M.M., N.A. and R.K.S.; Investigation, J.R., N.A., S.A. and J.M.; Resources, R.K.S. and C.J.C.; Data Curation, J.R. and N.A.; Writing—Original Draft Preparation, M.M. and R.K.S.; Writing—Review and Editing, J.R., N.A., J.M., C.J.C. and R.K.S.; Visualization, M.M. and R.K.S.; Supervision, R.K.S. and V.F.; Project Administration, J.R., N.A., S.A. and J.M.; Funding Acquisition, R.K.S. All authors have read and agreed to the published version of the manuscript. | PMC10574417 | ||
Institutional Review Board Statement | The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Allendale Institutional Review Board (protocol # SYW_01). | PMC10574417 | ||
Informed Consent Statement | Informed consent was obtained from all subjects involved in the study. | PMC10574417 | ||
Data Availability Statement | The data presented in this study are available on request from the corresponding author. | PMC10574417 | ||
Conflicts of Interest | R.K.S. serves as a scientific advisor for LearnHealth, Arbonne, and Codex Labs and has served as a consultant or speaker for Burt’s Bees, Novozymes, Biogena, Novartis, Sanofi, Bristol Myers Squibb, Pfizer, Nutrafol, Galderma, Novartis, Abbvie, Leo, UCB, Sun, and Regeneron Pharmaceuticals. J.M. serves as a scientific advisor for Codex Labs. All the other authors declare no conflict of interest. | PMC10574417 | ||
References | SKIN | CONSORT (Consolidated Standards of Reporting Trials) flow diagram.Computer-based photographic analysis of wrinkle severity was significantly decreased in the soy protein intervention group compared to the casein protein intervention group by −4.8% and −6.5% at week 16 and 24, respectively. Error bars represent the standard error of the mean (SEM). * = Computer-based photographic analysis of pigment intensity was significantly decreased in the soy protein intervention group compared to the casein protein intervention group by −2.5% at week 24. Error bars represent SEM. * = Skin hydration was measured resulting in a significant increase in hydration from baseline at week 24 in the (Sebum production did not change significantly in either the (Soy protein isolate with added isoflavones subject at baseline ( | PMC10574417 | |
Subject terms | major depression, cognitive symptoms, anxiety, psychic anxiety, reductions in affective symptoms, depressed mood, depression, Depression | The clinical response to selective serotonin reuptake inhibitors (SSRIs) in depression takes weeks to be fully developed and is still not entirely understood. This study aimed to determine the direct and indirect effects of SSRIs relative to a placebo control condition on clinical symptoms of depression. We included data of 8262 adult patients with major depression participating in 28 industry-sponsored US Food and Drug Administration (FDA) registered trials on the efficacy of SSRIs. Clinical symptoms of depression were assessed by the 17 separate items of the Hamilton Depression Rating Scale (HDRS) after 1, 2, 3, 4 and 6 weeks of treatment. Network estimation techniques showed that SSRIs had quick and strong direct effects on the two affective symptoms, i.e., depressed mood and psychic anxiety; direct effects on other symptoms were weak or absent. Substantial indirect effects were found for all four cognitive symptoms, which showed larger reductions in the SSRI condition but mainly in patients reporting larger reductions in depressed mood. Smaller indirect effects were found for two arousal/somatic symptoms via the direct effect on psychic anxiety. Both direct and indirect effects on sleep problems and most arousal/somatic symptoms were weak or absent. In conclusion, our study revealed that SSRIs primarily caused reductions in affective symptoms, which were related to reductions in mainly cognitive symptoms and some specific arousal/somatic symptoms. The results can contribute to disclosing the mechanisms of action of SSRIs, and has the potential to facilitate early detection of responders and non-responders in clinical practice. | PMC9867733 | |
Introduction | depression, psychic anxiety, depressed mood | The clinical response to selective serotonin reuptake inhibitors (SSRIs) in depression takes weeks to be fully developed [A recent comprehensive post hoc analysis [An interesting next step would be to focus on the interrelatedness of clinical symptoms. In the past decade, network estimation techniques have shown to be valuable in unraveling the complex relations between symptoms [SSRIs were directly related to larger reductions in the two considered affective symptoms (i.e., depressed mood and psychic anxiety), which were related to considerable reductions in specific other -mainly cognitive- symptoms [This will be the first study that uses network estimation techniques to shed light on the clinical response to SSRIs relative to placebo by considering individual symptoms after 1, 2, 3, 4 and 6 weeks of treatment. For this purpose, we used individual patient data from 28 industry-sponsored placebo-controlled SSRI trials as previously described [ | PMC9867733 | |
Methods | PMC9867733 | |||
Study design | major depression | We requested patient-level data for all industry-sponsored, US Food and Drug Administration- (FDA) registered, placebo-controlled, acute-phase, and HDRS-based trials of adults with major depression regarding citalopram from Lundbeck (Valby, Denmark), regarding paroxetine from GlaxoSmithKline (Brentford, UK), and regarding sertraline from Pfizer (New York, NY, USA). We obtained data from all relevant studies except for three small, prematurely terminated trials: GSK/07 (In total, we used data from 8262 patients with major depression who participated in 28 SSRI trials. Participants were treated with either citalopram ( | PMC9867733 | |
Assessment of clinical symptoms | Individual clinical symptoms were assessed by the separate items of the 17-item HDRS [ | PMC9867733 | ||
Statistical analyses | First, baseline characteristics were compared between the treatment conditions using All network estimations were performed using R (version 3.6.2). First, we examined the We also focused on the Lastly, we performed a set of sensitivity analyses. To evaluate the edge weight accuracy of the network models (at week 1, 2, 3, 4 and 6), we used the | PMC9867733 | ||
Results | PMC9867733 | |||
Baseline characteristics | Participants with complete data at one or more post-assessments (Baseline characteristics. | PMC9867733 | ||
The direct and indirect symptom-specific effects of SSRIs | To explore how the clinical response to SSRIs progressed over time, we estimated separate networks including treatment condition and symptom scores at 1, 2, 3, 4, and 6 weeks of treatment (see Fig. | PMC9867733 | ||
Direct effects | psychic anxiety, depressed mood | At almost all assessments, the strongest direct beneficial effects of SSRIs were found for the two affective symptoms, i.e., depressed mood (e.g., edge weight = −0.17 at week 6) and psychic anxiety (e.g., edge weight = −0.11 at week 6). The effect on depressed mood was already substantial at week 1 (i.e., edge weight = −0.09) and the effect on psychic anxiety at week 2 (edge weight = −0.09), and both became stronger in the following weeks. Other direct beneficial effects were much weaker at all assessment (i.e., edge weights ≥ −0.05 for all symptoms at all assessments).Interestingly, we also found some detrimental effects of active treatment. The detrimental effect of SSRIs on genital problems gradually increased over time, with an edge weight of 0.02 at week 1 and of 0.11 at week 6. The direct aggravating effect of SSRIs on loss of weight was initially high (i.e., edge weight of 0.16 at week 1) and decreased over time (i.e., edge weight of 0.03 at week 6). Other direct detrimental effects were much weaker (i.e., edge weights ≤ 0.06 for all other symptoms at all assessments). | PMC9867733 | |
Indirect effects | Figure | PMC9867733 | ||
Overall effects of SSRIs over time | Lastly, we focused on the overall symptom-specific effects of SSRIs at all assessments (i.e., not adjusted for other symptom-specific effects; Fig. | PMC9867733 | ||
Sensitivity analyses | psychic anxiety, depressed mood | To assess the accuracy of the most relevant edge weights in the estimated networks (Fig. To test the robustness of our network findings across trials, we estimated the networks while adjusting for trial-id and found no substantial differences in estimations; at week 6, for example, the beneficial effects of SSRIs on depressed mood (edge weight = −0.17) and psychic anxiety (edge weight = −0.12) and the detrimental effect on genital problems (edge weight = 0.11) were stable. Adjustment for age, which was significantly related to treatment condition (see the previous section on baseline characteristics), did also not substantially change the networks; at week 6, for example, the edge weights of SSRIs with depressed mood (edge weight = −0.17), psychic anxiety (edge weight = −0.11) and genital problems (edge weight = 0.11) remained the same. | PMC9867733 | |
Discussion | guilt, major depression, psychic anxiety, anxiety, reductions in affective symptoms, agitation, depressed mood, hypochondriasis | To the best of our knowledge, this is the first study that uses network estimation techniques to shed light on the complex clinical response of SSRIs relative to placebo over a 6-week period. The most profound direct effects of SSRIs were found for the two affective symptoms, for which the effect on depressed mood was slightly quicker and stronger than the one on psychic anxiety. Direct effects on other symptoms were weak or absent, except for two detrimental effects on genital problems and loss of weight. We observed substantial indirect effects on all four cognitive symptoms via the direct effect on depressed mood, whereas smaller indirect effects were found for two arousal/somatic symptoms (i.e., somatic anxiety and agitation) via the direct effect on psychic anxiety.It is well-established from numerous drug trials as well as from clinical experience that the antidepressant effect of SSRIs takes a few weeks to emerge and several weeks to be fully developed [To generate hypotheses regarding the potential mechanisms of clinical change during SSRI treatment, we used network estimation techniques to reveal the patterns according to which individual symptoms were related. The networks showed multiple connections (e.g., 75 unique connections at week 1 and 53 unique connections at week 6), illustrating the complexity of the clinical response to SSRIs. It is therefore unlikely that this clinical response is a consequence of a single mechanism; instead, many mechanisms are probably involved, which may also differ across individual patients. However, our network findings could be valuable in revealing pathways that potentially play a prominent role in the clinical response to SSRIs. For example, depressed mood was mainly related to cognitive symptoms at all assessments, which explains the substantially larger reductions in these symptoms in the SSRI condition relative to the placebo condition. From a clinical perspective, it is also intuitive that an improvement in mood increases, for example, a patient’s interest in work and activities and decreases his or her feelings of guilt and suicidal thoughts. Although to a lesser extent, psychic anxiety was mainly related to somatic anxiety and agitation (i.e., two arousal/somatic symptoms), suggesting that improvements in the psychological aspects of anxiety go hand in hand with improvements in physical aspects of anxiety as measured with these two symptoms; again, this makes sense from a clinical perspective.The presented networks also support the notion that the HDRS captures common side effects of SSRIs, which is in line with a recent study [A strength of the current study is that we used data of 7909 patients with major depression by combining 28 industry-sponsored, placebo-controlled SSRI trials and considered assessments after 1, 2, 3, 4 and 6 weeks. Consequently, we had sufficient statistical power to consider a broad spectrum of clinical outcomes and their complex interrelatedness.As a possible weakness of the study it should be noted that some reports have suggested the inter-rater reliability of some HDRS items to be poor [It is also important to note that regularization techniques in network estimations set very weak connections to zero [Another potential weakness of the current study is that the number of response categories of the HDRS items differ and the sensitivity to detect symptom-specific effects might be higher for items with more response categories. This was, however, not supported by our findings, as the strongest direct effects were found for the two affective symptoms (scored 0–4) and two specific arousal/somatic symptoms (scored 0–2) while only weak effects were found for, for example, hypochondriasis (scored 0–4).In conclusion, our explorative study shows that network estimation techniques are valuable in demonstrating the complexity of the clinical response to treatment and in identifying pathways that potentially play a prominent role herein. For example, we showed that SSRIs primarily resulted in reductions in affective symptoms, which were related to reductions in mainly cognitive symptoms and some arousal/somatic symptoms. This might be an important step in disclosing the mechanisms of action of SSRIs, and may also have potential in the early detection of responders and non-responders in clinical practice. | PMC9867733 | |
Supplementary information | The online version contains supplementary material available at 10.1038/s41398-022-02285-2. | PMC9867733 | ||
Acknowledgements | ALF | BRAIN | This research was funded by the Netherlands Organization for Health Research and Development (Zon-MW; grant number 016-186-139), Swedish Research Council (grant number 2020-02194), Swedish Brain Foundation (FO2018-0331) and Sahlgrenska University Hospital (grant number ALF 73300). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. | PMC9867733 |
Author contributions | LB conceived and designed the study and drafted the paper. LB also prepared the statistical analyses, while FH ran the scripts on the full dataset. FH and AL had full access to all data in the study, verified the data and take responsibility for the integrity of the data and the accuracy of the data analysis. EE supervised the study. All authors contributed to the critical revision of the paper for important intellectual content and approved the final paper and submission to Translational Psychiatry. | PMC9867733 | ||
Competing interests | Dr FH has received lecture honoraria from H Lundbeck and Servier. Professor EE has been on advisory boards or received lecture honoraria from H Lundbeck, Janssen‐Cilag and Servier. Dr LB, Dr AL, and professor PC report no financial relationships with commercial interests. | PMC9867733 | ||
References | PMC9867733 | |||
Introduction | basketball, FMS | FMS | Experts argue that participation in youth sports such as basketball is a healthy activity for youngsters [Although engagement in youth sports may contribute to the development of PL, early specialisation (which is defined as year-round participation and competition within a single sport [Despite the purported issues relating to early specialisation, some researchers argue that these issues are overly simplistic [In addition to enhancing athletic capabilities in youth athletes, the efficacy of NMT programmes may also relate to the variability of movement patterns presented within such programmes. Accordingly, the performance of varied movement patterns reduces the persistent mechanical stress on the same soft-tissue structures through repeated exposure to SSSs, while concomitantly developing a greater breadth of FMS [Previously, parkour has been proposed as an activity to develop FMS and athletic capabilities that can be transferred to SSS [ | PMC10337934 |
Materials and methods | PMC10337934 | |||
Participants | A total of 34 youth basketball players (mean age 11.4 ± 0.67 years) consented to participate in the in the pre-post study design across an 8-week intervention period. To increase homogeneity of the population sample [ | PMC10337934 | ||
Phase 1 –Quantitative measures and analysis | PMC10337934 | |||
Testing procedures | All testing was carried out by the first author and took place in gymnasiums across two sites used by the respective basketball clubs for regular practice. Testing took place one week before and after the eight-week intervention period and included: anthropometry (height, seated height, mass), overhead squat (OHS) assessment, countermovement jump (CMJ), 10-m sprint and, for the experimental groups only, a parkour speed-run. To estimate participant maturity status, anthropometric measures were recorded using medical grade digital scales and stadiometer (Seca, Birmingham, United Kingdom) and entered into a sex-specific equation to predict maturity offset [Girls: Maturity Offset (years) = -9.376 + (0.0001882 x (leg length x sitting height)) + (0.0022 x (age x leg length)) + (0.005841 x (age x sitting height))–(0.002658 x (age x mass)) + (0.07693 x (mass by stature ratio x 100));andBoys: Maturity offset (years) = -9.236 + (0.0002708 x (leg length x sitting height)) + (-0.001663 x (age x leg length)) + (0.007216 x (age x sitting height)) + (0.02292 x (mass by stature ratio x 100)).For the OHS assessment, participants were instructed to hold a wooden dowel with extended arms above the crown of their head and, while maintaining the OH position, squat as low as possible. Following three warm-up trials, three further repetitions were performed and recorded using the motion analysis system, HumanTrak (Vald Performance, Brisbane, Qld, Australia). The sum of knee flexion angle for both limbs for the OHS were averaged for the three repetitions and used in the analysis.To measure the CMJ, participants were required to jump with their hands placed upon their hips and instructed to descend to a self-selected countermovement depth before immediately jumping as high as possible. Following three warm-up trials, participants performed three test trials on dual portable force platforms (ForceDecks, Vald Performance, Brisbane, Qld, Australia), with at least 20 seconds between trials. The average of the three jumps were analysed.For acceleration speed, electronic timing gates were used (Brower Timing Systems, Draper, Utah, USA). Following a standardised warm-up comprising submaximal running efforts over a 10-m distance and two practice trials at maximal intensity, each participant completed three trials with at least 60-seconds recovery between trials. Participants began each trial in a The speed-run route was designed in accordance with Strafford et al. [ | PMC10337934 | ||
Training interventions | Participants of both experimental groups were required to complete a 15-minute warm-up once per week before their regular basketball practice across 8-weeks. The warm-up was led by the principal researcher (also a qualified S&C coach) and conducted in the same school gymnasium located in a separate building to the basketball practice. While one group completed their intervention, the other group completed low intensity shooting exercises with their basketball coach. This was portrayed to the players to relate to limited space available in the warm-up location. However, to account for any impact of the shooting exercises, the order by which each group completed the intervention (before or after shooting) was alternated each week. To ensure the time of the warm-ups was matched, a timer was set for 15-minutes and commenced upon the explanation of the first activity / exercise of each of the respective warm-ups.The details of the included exercises for both warm-ups are found in | PMC10337934 | ||
Exercises and activities included within the 15-minute warm-up for the respective experimental groups. | PMC10337934 | |||
Data analysis | Within subject coefficient of variation (CV) and average CV measures for each test were determined using the spreadsheet software, Microsoft Excel (Microsoft Office 365). ICC calculation and inferential analyses were performed using the statistical analysis software, IBM SPSS Statistics for Windows, version 28.0. All measures were tested for normality using the Shapiro-Wilk test and for homogeneity using the Levene’s test. To evaluate mean differences across the multiple variables, a Repeated Measures MANOVA was used to assess differences by group and time between pre- and post-testing for all three groups and across all measures except for the parkour speed-run. For the speed-run, a Repeated Measures ANOVA was used to assess differences by group and time.In addition, due to the low dose application of the warm-up protocols, Cohen’s | PMC10337934 | ||
Phase 2 Qualitative data and analysis | PMC10337934 | |||
Semi-structured interviews | Ponizovsky-Bergelson et al. | Based upon recommendations by Ponizovsky-Bergelson et al. [ | PMC10337934 | |
Data analysis | A thematic analysis was undertaken using the codes developed through three rounds of iterative coding. In addition, inductive analysis technique were also utlised in the analysis of the transcripts, creating additional codes deemed to be pertinent to the study aims (see for e.g., Fereday and Muir-Cochrane, [ | PMC10337934 | ||
Results | Having been calculated to be approximately classified as either circa- or post-PHV, five participants were removed from the analysis. Additionally, due to low adherence levels (< 6 from a total of 9 exposures), a further three participants’ data were removed from the analysis. In addition, one participant was removed due to injury. Therefore, a total of 18 participants who met the inclusion criteria relating to adherence, maturity status, and at least one year of participation in basketball were included in the statistical analyses ( | PMC10337934 | ||
Average physical characteristics of the participants by group. | PMC10337934 | |||
Descriptive pre- and post-intervention test measures. | ± | Means, standard deviations (±) and within-group Cohen’s A high degree of reliability was found between familiarisation scores and the pre-intervention test scores for the speed-run. Based on an absolute agreement, 2-way mixed-effects model, the ICC estimate was .963 with a 95% confidence interval from .600 to .994. The average CV for the familiarisation scores was 6.65%. Within subject variation (CV) values for all pre- and post-intervention tests are displayed in | PMC10337934 | |
Average pre- and post-intervention coefficient of variation (%) per group. | All pre- and post-intervention data was determined to be normally distributed (p > 0.5). The Repeated Measures MANOVA revealed no significant effects of group on pre-post intervention measures, The repeated measures ANOVA used for the analysis of the parkour-based speed run revealed no significant effects of time x group interaction on completion times, In the Conventional warm-up group, the within group ES values revealed a medium ES improvement in knee flexion angle in performance of the OHS. In contrast, the Parkour and Control groups displayed reductions in knee flexion angles with a medium and large ES, respectively. For the Conventional warm-up group, the Cohen’s Figs | PMC10337934 | ||
Individual pre-post intervention mean 10-m sprint data. | Dashed lines represent % changes > than pre-intervention CV; solid lines represent difference that was not > CV. | PMC10337934 | ||
Individual pre-post intervention mean Speed-Run data. | Dashed lines represent % changes > than pre-intervention CV; solid lines represent difference that was not > CV. | PMC10337934 | ||
Individual pre-post intervention mean CMJ data. | Dashed lines represent % changes > than pre-intervention CV; solid lines represent difference that was not > CV. | PMC10337934 | ||
Individual pre-post intervention mean Overhead Squat knee flexion data. | Dashed lines represent % changes > than pre-intervention CV; solid lines represent difference that was not > C. | PMC10337934 | ||
Qualitative findings | Data was categorised into three higher order themes drawing on data from the young players’ responses: enjoyment; physical literacy; and docility. These themes included subthemes that related to the young players’ reflections on the value and purpose of the warm-up intervention and perceived benefits on basketball playing performance (see | PMC10337934 | ||
Higher order themes and associated subthemes. | PMC10337934 | |||
Theme 1 – | Most participants indicated that they enjoyed the warm-up activities, irrespective of the experimental group they were assigned to:“Yeah, it’s definitely one of the things that I enjoy doing a lot because it’s not just like running there and back, but it’s including like jumps and then like moving around more rather than going in the straight line there and back.”With specific reference to parkour-based activities, participants also suggested that they found the warm-up to be fun. One individual commented:“I think honestly, I really like jumping over the things because I found it fun. It was like when and also jumping onto the mat. That was quite fun as well. And obviously the ropes at the end. That was just the fun.”Similarly, another individual stated:“Yeah, because it was it was [sic] a good time doing it. It was a good part of the day, like. Oh year, it’s fun.” | PMC10337934 | ||
Theme 2 – | Improved confidence in relation to movement competency and motor abilities was identified by the participants. In addition, participants displayed critical reflection of the activities prescribed and self-awareness of their movement capabilities. When asked whether the warm-up activities benefitted basketball, one participant reflected:“The rope swing? Yeah, I think those might be less applicable to basketball, but they still help upper body strength.”Another participant responded with:“For me, I think it was like during the sprint. Uh, because that was the bit that helped me the most. And also because because [sic] like it, it was a bit more competitive than most of the other warm ups we did.”And, another participant stated:“It helped me like [sic] control my speed levels…I can like [sic] fake it” | PMC10337934 | ||
Theme 3 – | In some of the participants, docility was detected through responses that conveyed an indifferent attitude or appeared to indicate a level of performativity. In response to whether they enjoyed the warm-up activities one individual commented:“I don’t know. I can’t think right now that nothing was not fun. I liked it.”Another individual stated:“Like the obstacle course, all the stuff we did. And, yeah.” | PMC10337934 | ||
Discussion | knee flexion | The results of the quantitative phase of our study revealed no differences between conventional neuromuscular training exercises and parkour-based actions when utilised within the warm-up protocols of pre-PHV basketball players. In relation to the Conventional warm-up group, our findings appear to contradict previous studies that have highlighted the efficacy of NMT-based warm-up programmes [In addition to the pedagogical delivery strategy, another possible explanation for our results may relate to the frequency of the warm-up exposure being limited to once per week. Typically, studies that have highlighted the efficacy of NMT-based warm-ups have prescribed two exposures per week (e.g., [Notwithstanding the results of our multivariate analyses, comparisons of within-group ES values for pre-post measures appeared to demonstrate that some specific adaptations were elicited in response to the stimuli of the respective warm-up programmes. Specifically, there were observed improvements in speed-related measures for the Conventional group, whereas both the Parkour and control groups showed a tendency to worsen in 10-m sprint performance, the largest effect of which was found in the control group. In the parkour-based speed-run test, however, while the largest within-group effect size was found for the Conventional group, the Parkour group also showed improvements in performance. In contrast, pre-post measures for the CMJ did not reveal any distinct changes, with very small effect sizes across all three groups. In the OHS knee flexion angles were found to improve with moderate effect sizes in the Conventional group and worsen in the Parkour and control groups. However, as might be expected, irrespective of group, at an individual level, each of the test measures revealed mixed results with some participants appearing to either show positive or negative changes greater than their pre-intervention CV. Thus, despite good levels of pre- and post-test reliability, the observed effect sizes were somewhat influenced by outliers, with some participants displaying substantially large differences between pre- and post-intervention measures, perhaps highlighting challenges associated with physical testing for empirical studies in preadolescent youths. In this regard it has previously been highlighted that in younger athletic populations, there may be increased variability in test performance due to limited physical development [Despite both warm-up interventions potentially preserving the young athletes’ physical fitness qualities, the medium to large between group ES, taken with the within-group ES difference across groups, appear to suggest that, for certain qualities, the Conventional warm-up was more effective than the Parkour-based warm-up. For example, the Conventional group’s exposure to acceleration speed is a likely explanation for their improvement in measure for 10-m sprint speed compared to the other groups. This may also account for the observed differences in OHS knee flexion achieved by the Conventional group compared to the Parkour and control groups. While the OHS was purposefully not included in the Conventional group’s warm-up, a bodyweight squat pattern (with arms held in front of the body) was included in each training session. Where the ability to perform a bodyweight squat to a depth of at least 90˚of knee flexion (or thighs parallel to the floor) is considered an indication of movement quality and neuromuscular control and movement skill [Somewhat contradicting to the apparent specific responses to the respective warm-up interventions’ content is observed in the Parkour group’s small ES value for the CMJ, despite being characterised by a greater volume of jumping and leaping activities compared to the Conventional group. However, as indicated by the observed changes across the groups against the pre-intervention CV values, there appeared to somewhat similar patterns of improvement in response to the different two warm-up interventions. A plausible explanation, therefore, is that the lack of prescription of exercise repetitions / foot contacts in the Parkour group in comparison to typical NMT-based warm-up programmes that prescribe progressively increasing volumes for each exercise (e.g., FIFA-11+). Indeed, the comparative results for the Conventional group, suggest that the low-structured prescription of exercises that characterised both interventions may have limited the development of jumping-related qualities.In summary, our quantitative results suggest that 15-minute NMT-based warm-up interventions offer some preservative benefits to the physical fitness qualities of pre-PHV athlete group. Moreover, as indicated in the results of the Parkour group’s warm-up intervention versus the control, there is potential merit to the incorporation of less conventional activities and exercises with the youth athletic development strategy. | PMC10337934 | |
Qualitative research better psycho-social and embodied outcomes consistent with phenomenological definitions of PL | The thematic analysis revealed that the intervention warm-ups may have aligned to the concept of holistic development of the young basketball players that is typically emphasised within youth athletic development literature [While the Parkour warm-up group indicated greater levels of enjoyment, both groups appeared to display self-reflection and critical thought in relation to the included activities. In this regard, the responses contributed to the theme “The above example highlights the wider implications of the warm-up that extend to psychological-based outcomes. In relation to this, PL extends beyond physical capacities and encompasses perception, memory, experience and decision-making [The third and final theme, | PMC10337934 | ||
Conclusions | FMS | Collectively, the results of our two investigations suggest that NMT-based warm-ups can be effective in the broader development of pre-adolescent basketball players beyond the typical aims and objectives of athletic development. Although limited, our findings highlight potential benefits of parkour-related activities alongside typical neuromuscular-focused exercises, as part of the youth athletic development strategy. Despite low frequency of exposure, the incorporation of less conventional approaches, such as the use of parkour-related activities within a low structured learning environment, may at the very least, preserve athletic capabilities ahead of PHV. Moreover, from a holistic perspective, this approach would appear to contribute to broader aims of PL, including the development of FMS and qualities of physical fitness (e.g., speed, strength, jumping ability), critical reflection, and self-confidence, while evoking a combined sense of enjoyment, fun, and purpose. | PMC10337934 | |
Supporting information | (XLSX)Click here for additional data file. | PMC10337934 | ||
Abstract | vascular dysfunction | High sodium diets (HSD) can cause vascular dysfunction, in part due to increases in reactive oxygen species (ROS). Melatonin reduces ROS in healthy and clinical populations and may improve vascular function. The purpose was to determine the effect of melatonin supplementation on vascular function and ROS during 10 days of a HSD. We hypothesized that melatonin supplementation during a HSD would improve vascular function and decrease ROS levels compared to HSD alone. Twenty‐seven participants (13 M/14 W, 26.7 ± 2.9 years, BMI: 23.6 ± 2.0 kg/m
| PMC10727961 | |
INTRODUCTION | macrovascular and microvascular function | SECONDARY | The average sodium intake in the United States is ~3500 mg/day while the Dietary Reference Intakes recommend ≤2300 mg/day (Stallings et al., Melatonin is a hormone synthesized in the pineal gland predominantly at night and has been shown to have antioxidant properties (Tengattini et al., Therefore, the primary aim of this study was to determine the effect of melatonin supplementation during 10 days of a HSD on macrovascular and microvascular function. Our secondary aim was to determine the effect of melatonin during 10 days of a HSD on ROS levels. We hypothesized that melatonin supplementation during 10 days of a HSD would lead to greater vascular function and lower ROS compared to a HSD plus placebo. | PMC10727961 |
MATERIALS AND METHODS | PMC10727961 | |||
Participants | The study protocol was approved by the Institutional Review Board of the University of Delaware and conformed to the provisions of the Declaration of Helsinki. The study was registered on Participants completed a medical history questionnaire, a menstrual cycle form (women only), and a global physical activity questionnaire (GPAQ) (Armstrong & Bull, | PMC10727961 | ||
Experimental protocol | This was a randomized double‐blind placebo‐controlled crossover study which consisted of two 10‐day conditions separated by a washout period of at least 14 days. During both conditions, participants consumed salt pills and supplemented with either 10 mg of melatonin (HSD + MEL) or a lactose placebo (HSD + PL) capsule daily. Melatonin and placebo capsules were manufactured by SaveWay compounding pharmacy (Newark, DE) and were matched in weight and appearance. The melatonin was purchased from Letco by Fargon Medical and had the USP designation. Participants were instructed to take the capsule 30 min before going to sleep. The dose of melatonin used has been shown to decrease ROS in clinical populations with no reported side effects (Raygan et al., | PMC10727961 | ||
Sleep assessment | Participants wore wrist accelerometers (Motionlogger Micro watch, Ambulatory Monitory Inc, Tokyo, Japan) on their nondominant wrist for 9 days and nights, except for activities involving water. Data were collected in the zero‐crossing mode (ZCM) and saved in 1‐min epochs. The University of California San Diego algorithm, which is validated to produce accurate and reliable sleep estimates relative to polysomnography (Jean‐Louis et al., | PMC10727961 | ||
Urine collection | Participants collected their urine for 24 h starting on Day 9. Urine was assessed for volume, urine specific gravity (Goldberg Brix Refractometer, Reichert Technologies, Depew, NY), electrolyte concentrations (EasyElectrolyte Analyzer, Medica, Bedford, MA), and osmolality (Advanced 3D3 Osmometer, Advanced Instruments, ON, Canada). Urine flow rate was calculated and used to determine 24‐h sodium excretion. Urine collections were considered valid if collected within 20–28 h, there were not ≥2 missed collections, and volume was ≥500 mL. The first morning void was collected separately on Day 10 to assess melatonin compliance by measuring urinary 6‐sulfatoxymelatonin (ELISA kit, Alpco, Salem, NH). A 4 Parameter Logistics curve fit was used to obtain the calibrator curve with SoftMax Pro Software (Molecular Devices). Values at or above the maximum detectable level of the assay were assigned that value for statistical analysis purposes. | PMC10727961 | ||
Experimental visit | Experimental visits were scheduled in the morning (7 | PMC10727961 | ||
Macrovascular function | DILATION | Brachial artery flow‐mediated dilation (FMD) was performed according to established guidelines as an assessment of macrovascular function (Thijssen et al., | PMC10727961 | |
Microvascular function | vascular occlusion | VASCULAR OCCLUSION | Near‐infrared spectroscopy (NIRS) and a vascular occlusion test (VOT) were performed as a test of microvascular function following established guidelines (Barstow, | PMC10727961 |
Oxidative stress measurement | Electron paramagnetic resonance (EPR) was used to measure O | PMC10727961 | ||
Statistical analysis | Our primary outcome was brachial artery FMD measured on Day 10 of each condition. Secondary outcomes included TSI reperfusion slope and TSI AUC acquired from the NIRS‐VOT. An a priori power analysis determined that a sample size of 21 participants provided 95% power to detect a difference in FMD of at least 1% (effect size 0.83) at the end of the two arms using a paired samples | PMC10727961 | ||
RESULTS | vascular occlusion | DILATION, VASCULAR OCCLUSION, REACTIVE HYPEREMIA | Participant screening characteristics and blood chemistries for the 27 participants who completed this study are presented in Table Screening characteristics.Abbreviations: BMI, body mass index; BP, blood pressure; BUN, blood urea nitrogen; eGFR, estimated glomerular filtration rate; HDL, high‐density lipoprotein; LDL, low‐density lipoprotein; MAP, mean arterial pressure; VLDL, very‐low‐density lipoprotein.
Table Participant characteristics on Day 10 of each intervention.Abbreviations: BP, blood pressure; HDL, high‐density lipoprotein; HSD + MEL, high sodium diet plus melatonin; HSD + PL, high sodium plus placebo (lactose); LDL, low‐density lipoprotein; MAP, mean arterial pressure; VLDL, very‐low‐density lipoprotein.
Vascular function results collected on Day 10 of each condition are presented in Table Vascular function on Day 10 of each condition.Abbreviations: AUC, area under the curve; FMD, flow‐mediated dilation; HSD + MEL, high sodium diet plus melatonin; HSD + PL, high sodium diet plus placebo (lactose); NIRS‐VOT, near‐infrared spectroscopy with vascular occlusion test; TSI, tissue oxygenation index; TSI
Macrovascular function assessed via brachial artery flow‐mediated dilation (FMD) at the end of the high sodium diet plus placebo condition (HSD + PL) and at the end of the high sodium diet plus melatonin condition (HSD + MEL). (a) Relative FMD; (b) Shear rate area under the curve (AUC) to peak reached during reactive hyperemia. Microvascular function assessed via near‐infrared spectroscopy during vascular occlusion test (NIRS‐VOT) at the end of the high sodium diet plus placebo condition (HSD + PL) and at the end of the high sodium diet plus melatonin condition (HSD + MEL). (a), Slope 2, also known as reperfusion slope; (b) Tissue saturation index area under the curve (TSI AUC). ROS were measured as a potential mechanism by which melatonin may exert its antioxidant effects. We found no difference in superoxide between conditions as assessed by nitroxide molarity and free radical number as depicted in Figure Reactive oxygen species (ROS) at the end of the high sodium diet plus placebo condition (HSD + PL) and the high sodium diet plus melatonin condition (HSD + MEL). (a) Nitroxide concentration; (b) total number of free radicals. | PMC10727961 |
DISCUSSION | impaired microvascular function | OXIDATIVE STRESS | We performed a randomized controlled crossover trial in young, healthy, normotensive adults to evaluate the effect of melatonin during a HSD on vascular function. Melatonin has been shown to have antioxidant‐like properties and has been effective in reducing oxidative stress in clinical populations as well as improving cardiovascular biomarkers (Kedziora‐Kornatowska et al., We measured vascular function following 10 days of a HSD, achieved using salt pills. Previous work using salt pills to increase sodium intake over 10 days has shown a reduction in brachial artery FMD in young healthy adults compared to a recommended sodium diet (Babcock et al., Microvascular function was evaluated using NIRS‐VOT in addition to FMD. Changes in the microvasculature can often present before changes in larger conduit vessels highlighting the importance of examining the microvasculature (Holowatz et al., We have previously demonstrated that ROS scavengers can mitigate impaired microvascular function imposed by a HSD using a controlled feeding study approach (Greaney et al., | PMC10727961 |
Limitations | While we utilized a randomized, crossover design, we did not collect baseline measures and can only compare our outcomes on day 10. Due to this design, we did not control for the menstrual cycle phase in our female participants. Studies have shown no difference in FMD between distinct phases of the menstrual cycle in premenopausal women (Shenouda et al., | PMC10727961 | ||
CONCLUSIONS | macrovascular or microvascular function, inflammation | INFLAMMATION | In conclusion, our findings showed that 10 days of melatonin supplementation (10 mg/d) did not improve macrovascular or microvascular function compared to a placebo and did not decrease ROS in our sample of young healthy normotensive adults consuming a HSD. Future studies should investigate different melatonin doses and durations, explore mechanisms beyond ROS formation, such as inflammation and antioxidant defense systems, and examine other populations. | PMC10727961 |
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