Blood Flow Restricted Training and Time Trial Performance: A Cohort Study of World Class Rowers.

INTRODUCTION: This study aimed to explore the potential impact of incorporating blood-flow restriction (BFR) training within a training block characterized by minimal high-intensity work on 2000-m rowing ergometer time-trial (TT) performance in elite/world-class rowers. Physiological markers often associated with endurance performance (maximal aerobic capacity - VO2max, blood lactate thresholds and hemoglobin mass - Hbmass) were measured to determine whether changes are related to an improvement in performance. METHODS: Using a quasi-experimental, observational study design (no control group), 2000-m TT performance, VO2max, submaximal work rates eliciting blood lactate concentrations of ~2 and ~ 4 mmol·L-1, and Hbmass were measured before and after 4 weeks of non-competitive season training, which included BFR rowing. BFR training consisted of 11 sessions of 2x10 minutes of BFR rowing at a workload equating to blood lactate concentrations of ~2 mmol·L-1. Paired t-tests were used to compare pre/post values, and Pearson correlation was used to examine whether physiological changes were associated with changes to TT performance. RESULTS: TT performance improved in both female (1.09 ± 1.2%, ~4.6 ± 5.2 s; p < 0.01) and male (1.17 ± 0.48%, ~4.5 ± 1.9 s; p < 0.001) athletes. VO2max increased in female rowers only (p < 0.01), but both sexes had an increase in work rates eliciting blood lactate concentrations of 2 (female:184 ± 16 to 195 ± 15 W, p < 0.01; male:288 ± 23 to 317 ± 26 W, p = 0.04) and 4 mmol·L-1 (female:217 ± 13 to 227 ± 14 W, p = 0.02; male:339 ± 43 to 364 ± 39 W, p < 0.01). No changes in Hbmass (both sexes, p = 0.8) were observed. Improvements in TT performance were not related to physiological changes (all correlations p ≥ 0.2). CONCLUSIONS: After 4 weeks of training with BFR, the improvement in TT performance was greater than what is typical for this population. Physiological variables improved during this training block but did not explain improved TT performance.

Effect of Menstrual Cycle Phase and Hormonal Contraceptives on Resting Metabolic Rate and Body Composition.

The cyclical changes in sex hormones across the menstrual cycle (MC) are associated with various biological changes that may alter resting metabolic rate (RMR) and body composition estimates. Hormonal contraceptive (HC) use must also be considered given their impact on endogenous sex hormone concentrations and synchronous exogenous profiles. The purpose of this study was to determine if RMR and dual-energy X-ray absorptiometry body composition estimates change across the MC and differ compared with HC users. This was accomplished during a 5-week training camp involving naturally cycling athletes (n = 11) and HC users (n = 7 subdermal progestin implant, n = 4 combined monophasic oral contraceptive pill, n = 1 injection) from the National Rugby League Indigenous Women's Academy. MC phase was retrospectively confirmed via serum estradiol and progesterone concentrations and a positive ovulation test. HC users had serum estradiol and progesterone concentrations assessed at the time point of testing. Results were analyzed using general linear mixed model. There was no effect of MC phase on absolute RMR (p = .877), relative RMR (p = .957), or dual-energy X-ray absorptiometry body composition estimates (p > .05). There was no effect of HC use on absolute RMR (p = .069), relative RMR (p = .679), or fat mass estimates (p = .766), but HC users had a greater fat-free mass and lean body mass than naturally cycling athletes (p = .028). Our findings suggest that RMR and dual-energy X-ray absorptiometry body composition estimates do not significantly differ due to changes in sex hormones in a group of athletes, and measurements can be compared between MC phases or with HC usage without variations in sex hormones causing additional noise.

How Cool is That? The Effects of Menthol Mouth Rinsing on Exercise Capacity and Performance: A Systematic Review and Meta-analysis.

BACKGROUND: Menthol (MEN) mouth rinsing (MR) has gained considerable interest in the athletic population for exercise performance; however, the overall magnitude of effect is unknown. OBJECTIVE: The aim of this systematic review and meta-analysis was to determine the efficacy of menthol MEN MR and the impact it has on exercise capacity and performance. METHODS: Three databases were searched with articles screened according to the inclusion/exclusion criteria. Three-level meta-analyses were used to investigate the overall efficacy of MEN MR and the impact it has on exercise capacity and performance. Meta-regressions were then performed with 1) mean VO2peak, 2) MEN swilling duration; 3) the MEN concentration of MR solution, 4) the number of executed swills throughout a single experiment, 5) the use of flavoured sweetened, non-caloric, or non-flavoured neutral solutions as controls, 6) mean environmental temperature at the time of exercise tests, and 7) exercise type as fixed factors to evaluate their influence on the effects of MEN MR. RESULTS: Ten MEN MR studies included sufficient information pertaining to MEN MR and exercise performance and capacity. MR with MEN resulted in no significant change in capacity and performance (SMD = 0.12; 95% CI - 0.08, 0.31; p = 0.23, n = 1, tau21 < 0.0001, tau22 = < 0.0001, I2 = 0%). No significant influence was detected in meta-regressions for VO2peak, (estimate: 0.03; df = 8; 95% CI - 0.03, 0.09; p = 0.27), swilling duration (5 vs. 10 s: 0.00; df = 16; 95% CI - 0.41, 0.41; p = 1.0), MEN concentration (low [0.01%] vs. high [0.1%]: - 0.08; df = 15; 95% CI - 0.49, 0.32; p = 0.67), number of swills (estimate: 0.02; df = 13; 95% CI - 0.05, 0.09; p = 0.56), the use of flavoured sweetener or non-caloric as control (non-flavoured vs. flavoured: 0.12; df = 16; 95% CI - 0.30, 0.55; p = 0.55) or mean room temperature during exercise tests (estimate: 0.01; df = 16; 95% CI - 0.02, 0.04; p = 0.62). CONCLUSION: MEN MR did not significantly improve overall exercise capacity and performance, though those involved in endurance exercise may see benefits.

Direct and indirect impact of low energy availability on sports performance.

Low energy availability (LEA) occurs inadvertently and purposefully in many athletes across numerous sports; and well planned, supervised periods with moderate LEA can improve body composition and power to weight ratio possibly enhancing performance in some sports. LEA however has the potential to have negative effects on a multitude of physiological and psychological systems in female and male athletes. Systems such as the endocrine, cardiovascular, metabolism, reproductive, immune, mental perception, and motivation as well as behaviors can all be impacted by severe (serious and/or prolonged or chronic) LEA. Such widely diverse effects can influence the health status, training adaptation, and performance outcomes of athletes leading to both direct changes (e.g., decreased strength and endurance) as well as indirect changes (e.g., reduced training response, increased risk of injury) in performance. To date, performance implications have not been well examined relative to LEA. Therefore, the intent of this narrative review is to characterize the effects of short-, medium-, and long-term exposure to LEA on direct and indirect sports performance outcomes. In doing so we have focused both on laboratory settings as well as descriptive athletic case-study-type experiential evidence.

Effect of menstrual cycle and contraceptive pill phase on aspects of exercise physiology and athletic performance in female athletes: protocol for the Feminae international multisite innovative project.

The idiom 'more high-quality research is needed' has become the slogan for sport and exercise physiology-based research in female athletes. However, in most instances, it is challenging to address this gap of high-quality research in elite female athletes at a single study site due to challenges in recruiting enough participants with numerous menstrual cycle and contraceptive pill permutations. Accordingly, we have assembled an international multisite team to undertake an innovative project for female athletes, which investigates the effects of changes in endogenous and exogenous oestrogen and progesterone/progestins across the menstrual cycle and in response to second-generation combined monophasic contraceptive pill use, on aspects of exercise physiology and athletic performance. This project will employ the current gold-standard methodologies in this area, resulting in an adequately powered dataset. This protocol paper describes the consortium-based approach we will undertake during this study.

Feminae: an international multisite innovative project for female athletes.

Sufficient high-quality studies in sport science using women as participants are lacking, meaning that our knowledge and understanding of female athletes in relation to their ovarian hormone profiles is limited. Consortia can be used to pool talent, expertise and data, thus accelerating our learning on a given topic and reducing research waste through collaboration. To this end, we have assembled an international multisite team, described here, to investigate the effects of the menstrual cycle and contraceptive pill phase on aspects of exercise physiology and sports performance in female athletes. We intend to produce an adequately powered, high-quality dataset, which can be used to inform the practices of female athletes. Our approach will also employ research transparency-through the inclusion of a process evaluation-and reproducibility-through a standardised study protocol.

Review of the scientific rationale, development and validation of the International Olympic Committee Relative Energy Deficiency in Sport Clinical Assessment Tool: V.2 (IOC REDs CAT2)-by a subgroup of the IOC consensus on REDs.

Relative Energy Deficiency in Sport (REDs) has various different risk factors, numerous signs and symptoms and is heavily influenced by one's environment. Accordingly, there is no singular validated diagnostic test. This 2023 International Olympic Committee's REDs Clinical Assessment Tool-V.2 (IOC REDs CAT2) implements a three-step process of: (1) initial screening; (2) severity/risk stratification based on any identified REDs signs/symptoms (primary and secondary indicators) and (3) a physician-led final diagnosis and treatment plan developed with the athlete, coach and their entire health and performance team. The CAT2 also introduces a more clinically nuanced four-level traffic-light (green, yellow, orange and red) severity/risk stratification with associated sport participation guidelines. Various REDs primary and secondary indicators have been identified and 'weighted' in terms of scientific support, clinical severity/risk and methodological validity and usability, allowing for objective scoring of athletes based on the presence or absence of each indicator. Early draft versions of the CAT2 were developed with associated athlete-testing, feedback and refinement, followed by REDs expert validation via voting statements (ie, online questionnaire to assess agreement on each indicator). Physician and practitioner validity and usability assessments were also implemented. The aim of the IOC REDs CAT2 is to assist qualified clinical professionals in the early and accurate diagnosis of REDs, with an appropriate clinical severity and risk assessment, in order to protect athlete health and prevent prolonged and irreversible outcomes of REDs.

Mapping the complexities of Relative Energy Deficiency in Sport (REDs): development of a physiological model by a subgroup of the International Olympic Committee (IOC) Consensus on REDs.

The 2023 International Olympic Committee (IOC) consensus statement on Relative Energy Deficiency in Sport (REDs) notes that exposure to low energy availability (LEA) exists on a continuum between adaptable and problematic LEA, with a range of potential effects on both health and performance. However, there is variability in the outcomes of LEA exposure between and among individuals as well as the specific manifestations of REDs. We outline a framework for a 'systems biology' examination of the effect of LEA on individual body systems, with the eventual goal of creating an integrated map of body system interactions. We provide a template that systematically identifies characteristics of LEA exposure (eg, magnitude, duration, origin) and a variety of moderating factors (eg, medical history, diet and training characteristics) that could exacerbate or attenuate the type and severity of impairments to health and performance faced by an individual athlete. The REDs Physiological Model may assist the diagnosis of underlying causes of problems associated with LEA, with a personalised and nuanced treatment plan promoting compliance and treatment efficacy. It could also be used in the strategic prevention of REDs by drawing attention to scenarios of LEA in which impairments of health and performance are most likely, based on knowledge of the characteristics of the LEA exposure or moderating factors that may increase the risk of harmful outcomes. We challenge researchers and practitioners to create a unifying and dynamic physiological model for each body system that can be continuously updated and mapped as knowledge is gained.

Methodology for studying Relative Energy Deficiency in Sport (REDs): a narrative review by a subgroup of the International Olympic Committee (IOC) consensus on REDs.

In the past decade, the study of relationships among nutrition, exercise and the effects on health and athletic performance, has substantially increased. The 2014 introduction of Relative Energy Deficiency in Sport (REDs) prompted sports scientists and clinicians to investigate these relationships in more populations and with more outcomes than had been previously pursued in mostly white, adolescent or young adult, female athletes. Much of the existing physiology and concepts, however, are either based on or extrapolated from limited studies, and the comparison of studies is hindered by the lack of standardised protocols. In this review, we have evaluated and outlined current best practice methodologies to study REDs in an attempt to guide future research.This includes an agreement on the definition of key terms, a summary of study designs with appropriate applications, descriptions of best practices for blood collection and assessment and a description of methods used to assess specific REDs sequelae, stratified as either Preferred, Used and Recommended or Potential Researchers can use the compiled information herein when planning studies to more consistently select the proper tools to investigate their domain of interest. Thus, the goal of this review is to standardise REDs research methods to strengthen future studies and improve REDs prevention, diagnosis and care.

2023 International Olympic Committee's (IOC) consensus statement on Relative Energy Deficiency in Sport (REDs).

Relative Energy Deficiency in Sport (REDs) was first introduced in 2014 by the International Olympic Committee's expert writing panel, identifying a syndrome of deleterious health and performance outcomes experienced by female and male athletes exposed to low energy availability (LEA; inadequate energy intake in relation to exercise energy expenditure). Since the 2018 REDs consensus, there have been >170 original research publications advancing the field of REDs science, including emerging data demonstrating the growing role of low carbohydrate availability, further evidence of the interplay between mental health and REDs and more data elucidating the impact of LEA in males. Our knowledge of REDs signs and symptoms has resulted in updated Health and Performance Conceptual Models and the development of a novel Physiological Model. This Physiological Model is designed to demonstrate the complexity of either problematic or adaptable LEA exposure, coupled with individual moderating factors, leading to changes in health and performance outcomes. Guidelines for safe and effective body composition assessment to help prevent REDs are also outlined. A new REDs Clinical Assessment Tool-Version 2 is introduced to facilitate the detection and clinical diagnosis of REDs based on accumulated severity and risk stratification, with associated training and competition recommendations. Prevention and treatment principles of REDs are presented to encourage best practices for sports organisations and clinicians. Finally, methodological best practices for REDs research are outlined to stimulate future high-quality research to address important knowledge gaps.

Comparison of Bone Quality Among Winter Endurance Athletes with and Without Risk Factors for Relative Energy Deficiency in Sport (REDs): A Cross-Sectional Study.

Relative Energy Deficiency in Sport (REDs) is a syndrome describing the relationship between prolonged and/or severe low energy availability and negative health and performance outcomes. The high energy expenditures incurred during training and competition put endurance athletes at risk of REDs. The objective of this study was to investigate differences in bone quality in winter endurance athletes classified as either low-risk versus at-risk for REDs. Forty-four participants were recruited (M = 18; F = 26). Bone quality was assessed at the distal radius and tibia using high resolution peripheral quantitative computed tomography (HR-pQCT), and at the hip and spine using dual X-ray absorptiometry (DXA). Finite element analysis was used to estimate bone strength. Participants were grouped using modified criteria from the REDs Clinical Assessment Tool Version 1. Fourteen participants (M = 3; F = 11), were classified as at-risk of REDs (≥ 3 risk factors). Measured with HR-pQCT, cortical bone area (radius) and bone strength (radius and tibia) were 6.8%, 13.1% and 10.3% lower (p = 0.025, p = 0.033, p = 0.027) respectively, in at-risk compared with low-risk participants. Using DXA, femoral neck areal bone density was 9.4% lower in at-risk compared with low-risk participants (p = 0.005). At-risk male participants had 21.9% lower femoral neck areal bone density (via DXA) than low-risk males (p = 0.020) with no significant differences in females. Overall, 33.3% of athletes were at-risk for REDs and had lower bone quality than those at low-risk.

The Evolution of World-Class Endurance Training: The Scientist's View on Current and Future Trends.

BACKGROUND: Elite sport is continuously evolving. World records keep falling and athletes from a longer list of countries are involved. PURPOSE: This commentary was designed to provide insights into present and future trends associated with world-class endurance training based on the perspectives, experience, and knowledge of an expert panel of 25 applied sport scientists. RESULTS: The key drivers of development observed in the past 10-15 years were related to (1) more accessible scientific knowledge for coaches and athletes combined with (2) better integration of practical and scientific exchange across multidisciplinary perspectives within professionalized elite athlete support structures, as well as (3) utilization of new technological advances. Based on these perspectives, we discerned and exemplified the main trends in the practice of endurance sports into the following categories: better understanding of sport-specific demands; improved competition execution; larger, more specific, and more precise training loads; improved training quality; and a more professional and healthier lifestyle. The main areas expected to drive future improvements were associated with more extensive use of advanced technology for monitoring and prescribing training and recovery, more precise use of environmental and nutritional interventions, better understanding of athlete-equipment interactions, and greater emphasis on preventing injuries and illnesses. CONCLUSIONS: These expert insights can serve as a platform and inspiration to develop new hypotheses and ideas, encourage future collaboration between researchers and sport practitioners, and, perhaps most important, stimulate curiosity and further collaborative studies about the training, physiology, and performance of endurance athletes.

Female Athlete Representation and Dietary Control Methods Among Studies Assessing Chronic Carbohydrate Approaches to Support Training.

The aim of this audit was to assess the representation of female athletes, dietary control methods, and gold standard female methodology that underpins the current guidelines for chronic carbohydrate (CHO) intake strategies for athlete daily training diets. Using a standardized audit, 281 studies were identified that examined high versus moderate CHO, periodized CHO availability, and/or low CHO, high fat diets. There were 3,735 total participants across these studies with only ∼16% of participants being women. Few studies utilized a design that specifically considered females, with only 16 studies (∼6%) including a female-only cohort and six studies (∼2%) with a sex-based comparison in their statistical procedure, in comparison to the 217 studies (∼77%) including a male-only cohort. Most studies (∼72%) did not provide sufficient information to define the menstrual status of participants, and of the 18 studies that did, optimal methodology for control of ovarian hormones was only noted in one study. While ∼40% of male-only studies provided all food and beverages to participants, only ∼20% of studies with a female-specific design used this approach for dietary control. Most studies did not implement strategies to ensure compliance to dietary interventions and/or control energy intake during dietary interventions. The literature that has contributed to the current guidelines for daily CHO intake is lacking in research that is specific to, or adequately addresses, the female athlete. Redressing this imbalance is of high priority to ensure that the female athlete receives evidence-based recommendations that consider her specific needs.

Evaluation of Different Pressure-Based Foot Contact Event Detection Algorithms across Different Slopes and Speeds.

If validated, in-shoe pressure measuring technology allows for the field-based quantification of running gait, including kinematic and kinetic measures. Different algorithmic methods have been proposed to determine foot contact events from in-shoe pressure insole systems, however, these methods have not been evaluated for accuracy, reliability against a gold standard using running data across different slopes, and speeds. Using data from a plantar pressure measurement system, seven different foot contact event detection algorithms based on pressure signals (pressure sum) were compared to vertical ground reaction force data collected from a force instrumented treadmill. Subjects ran on level ground at 2.6, 3.0, 3.4, and 3.8 m/s, six degrees (10.5%) inclined at 2.6, 2.8, and 3.0 m/s, and six degrees declined at 2.6, 2.8, 3.0, and 3.4 m/s. The best performing foot contact event detection algorithm showed maximal mean absolute errors of only 1.0 ms and 5.2 ms for foot contact and foot off, respectively, on level grade, when compared to a 40 N ascending and descending force threshold from the force treadmill data. Additionally, this algorithm was unaffected by grade and had similar levels of errors across all grades.

Characterization of the Kinetyx SI Wireless Pressure-Measuring Insole during Benchtop Testing and Running Gait.

This study characterized the absolute pressure measurement error and reliability of a new fully integrated (Kinetyx, SI) plantar-pressure measurement system (PPMS) versus an industry-standard PPMS (F-Scan, Tekscan) during an established benchtop testing protocol as well as via a research-grade, instrumented treadmill (Bertec) during a running protocol. Benchtop testing results showed that both SI and F-Scan had strong positive linearity (Pearson's correlation coefficient, PCC = 0.86-0.97, PCC = 0.87-0.92; RMSE = 15.96 ± 9.49) and mean root mean squared error RMSE (9.17 ± 2.02) compared to the F-Scan on a progressive loading step test. The SI and F-Scan had comparable results for linearity and hysteresis on a sinusoidal loading test (PCC = 0.92-0.99; 5.04 ± 1.41; PCC = 0.94-0.99; 6.15 ± 1.39, respectively). SI had less mean RMSE (6.19 ± 1.38) than the F-Scan (8.66 ±2.31) on the sinusoidal test and less absolute error (4.08 ± 3.26) than the F-Scan (16.38 ± 12.43) on a static test. Both the SI and F-Scan had near-perfect between-day reliability interclass correlation coefficient, ICC = 0.97-1.00) to the F-Scan (ICC = 0.96-1.00). During running, the SI pressure output had a near-perfect linearity and low RMSE compared to the force measurement from the Bertec treadmill. However, the SI pressure output had a mean hysteresis of 7.67% with a 28.47% maximum hysteresis, which may have implications for the accurate quantification of kinetic gait measures during running.

Fueling the Female Athlete: Auditing Her Representation in Studies of Acute Carbohydrate Intake for Exercise.

PURPOSE: The aim of this audit was to assess the representation of female athletes within the literature that has led to current guidelines for carbohydrate (CHO) intake in the acute periods surrounding exercise and the quality of this research. METHODS: We conducted a standardized audit of research assessing CHO loading protocols, CHO mouth rinse, and CHO intake before, during, and after exercise. RESULTS: A total of 937 studies were identified in this audit. There were a total of 11,202 participants across these studies, with only ~11% being women. Most studies involved male-only cohorts (~79%), with a mere 38 studies (~4%) involving female-only cohorts and 14 studies (~2%) including a methodological design for comparison of sex-based responses. The frequent use of incorrect terminology surrounding menstrual status and the failure of most studies (~69%) to provide sufficient information on the menstrual status of participants suggests incomplete understanding and concern for female-specific considerations among researchers. Of the 197 studies that included women, only 13 (~7%) provided evidence of acceptable methodological control of ovarian hormones, and no study met all best-practice recommendations. Of these 13 studies, only half also provided sufficient information regarding the athletic caliber of participants. The topics that received such scrutiny were CHO loading protocols and CHO intake during exercise. CONCLUSIONS: The literature that underpins the current guidelines for CHO intake in the acute periods around exercise is lacking in high-quality research that can contribute knowledge specific to the female athlete and sex-based differences. New research that considers ovarian hormones and sex-based differences is needed to ensure that the recommendations for acute CHO fueling provided to female athletes are evidence based.

Effect of Pregnancy in 42 Elite to World-Class Runners on Training and Performance Outcomes.

PURPOSE: The International Olympic Committee expert group on pregnancy has identified a paucity of information regarding training and performance in truly elite athletes. Thus, the purpose of this study was to quantify elite runners' training volume throughout pregnancy and postpartum competition performance outcomes. METHODS: Forty-two elite (>50% competed at the World Championships/Olympic) middle-/long-distance runners' training before, during, and after pregnancy (quality/quantity/type) data (retrospective questionnaire) and competition data (published online) were collected. RESULTS: Running volume decreased significantly ( P < 0.01) from the first trimester (63 ± 34 km·wk -1 ) to the third trimester (30 ± 30 km·wk -1 ). Participants returned to activity/exercise at ~6 wk postpartum and to 80% of prepregnancy training volumes by 3 months. Participants who intended to return to equivalent performance levels postpregnancy, there was no statistical decrease in performance in the 1 to 3 yr postpregnancy compared with prepregnancy, and ~56% improved performances postpregnancy. CONCLUSIONS: This study features the largest cohort of elite runners training and competition outcomes assessed throughout pregnancy, with training volumes being approximately two to four times greater than current guidelines. For the first time, performance was directly assessed (due to the quantifiable nature of elite running), and study participants who intended to return to high-level competition did so at a statistically similar level of performance in the 1- to 3-yr period postpregnancy. Taken together, this article provides much needed insights into current training practices and performance of elite pregnant runners, which should help to inform future training guidelines as well as sport policy and sponsor expectations around return to training timelines and performance.

Managing Female Athlete Health: Auditing the Representation of Female versus Male Participants among Research in Supplements to Manage Diagnosed Micronutrient Issues.

Micronutrient deficiencies and sub-optimal intakes among female athletes are a concern and are commonly prevented or treated with medical supplements. However, it is unclear how well women have been considered in the research underpinning current supplementation practices. We conducted an audit of the literature supporting the use of calcium, iron, and vitamin D. Of the 299 studies, including 25,171 participants, the majority (71%) of participants were women. Studies with exclusively female cohorts (37%) were also more prevalent than those examining males in isolation (31%). However, study designs considering divergent responses between sexes were sparse, accounting for 7% of the literature. Moreover, despite the abundance of female participants, the quality and quantity of the literature specific to female athletes was poor. Just 32% of studies including women defined menstrual status, while none implemented best-practice methodologies regarding ovarian hormonal control. Additionally, only 10% of studies included highly trained female athletes. Investigations of calcium supplementation were particularly lacking, with just two studies conducted in highly trained women. New research should focus on high-quality investigations specific to female athletes, alongside evaluating sex-based differences in the response to calcium, iron, and vitamin D, thus ensuring the specific needs of women have been considered in current protocols involving medical supplements.