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Time-Course of Recovery for Biomarkers and Physical Performance after Strenuous Military Training : A Systematic Review

Granlund, Julius,Kyröläinen, Heikki,Santtila, Matti,Nindl, Bradley C.,Pihlainen, Kai,Ojanen, Tommi

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This is a self-archived version of an original article. This version may differ from the original in pagination and typographic details. Author(s): Title: Year: Version: Copyright: Rights: Rights url: Please cite the original version: CC BY 4.0 https://creativecommons.org/licenses/by/4.0/ Time-Course of Recovery for Biomarkers and Physical Performance after Strenuous Military Training : A Systematic Review © 2023 by the authors. Licensee MDPI, Basel, Switzerland. Published version Granlund, Julius; Kyröläinen, Heikki; Santtila, Matti; Nindl, Bradley C.; Pihlainen, Kai; Ojanen, Tommi Granlund, J., Kyröläinen, H., Santtila, M., Nindl, B. C., Pihlainen, K., & Ojanen, T. (2023). Time- Course of Recovery for Biomarkers and Physical Performance after Strenuous Military Training : A Systematic Review. Physiologia, 3(4), 627-641. https://doi.org/10.3390/physiologia3040046 2023 Citation: Granlund, J.; Kyröläinen, H.; Santtila, M.; Nindl, B.C.; Pihlainen, K.; Ojanen, T. Time-Course of Recovery for Biomarkers and Physical Performance after Strenuous Military Training: A Systematic Review. Physiologia 2023,3, 627–641. https://doi.org/10.3390/ physiologia3040046 Academic Editor: Anastassios Philippou Received: 18 October 2023 Revised: 5 November 2023 Accepted: 11 December 2023 Published: 13 December 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Systematic Review Time-Course of Recovery for Biomarkers and Physical Performance after Strenuous Military Training: A Systematic Review Julius Granlund 1, Heikki Kyröläinen 1,2 , Matti Santtila 2, Bradley C. Nindl 3, Kai Pihlainen 4 and Tommi Ojanen 5,* 1Neuromuscular Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, 40014 Jyväskylä, Finland 2Department of Leadership and Military Pedagogy, National Defence University, 00861 Helsinki, Finland 3 Neuromuscular Research Laboratory/Warrior Human Performance Research Center, University of Pittsburgh, Pittsburgh, PA 15203, USA 4Training Division, Defence Command, 00130 Helsinki, Finland 5Human Performance Division, Finnish Defence Research Agency, 04310 Tuusula, Finland *Correspondence: [email protected] Abstract: The objective of the present review was to evaluate the time-course of recovery of biochemical marker levels and physical performance after strenuous military training, and identify which biomarkers are affected. A systematic literature search was conducted using the databases MedLine (Ovid) and Web of Science (WoS) to identify studies until January 2023. Varying relevant search terms were used, related to military training, Special Forces, physical performance, and biomarkers. Records were based on strict inclusion and exclusion criteria. Twelve studies met the inclusion criteria and were selected for this review. A variety of physiological and psychological markers were measured, and military training lasted from 4 to 62 days, with recovery periods varying from 24 h to 6 weeks. Among these studies, full recovery was observed in two studies, while seven studies showed almost full (79–90%) recovery, and in three studies, 44–63% of markers recovered after the measured recovery period. However, in some studies, additional markers could be defined as recovered, depending on the criterion for recovery. In the majority of the studies, most of the measured variables recovered during the follow-up, but often, some variables remained unrecovered, and at times, only modest recovery was seen. It is important to point out that recovery duration depends on the duration and intensity of the military training stressor. Overall, resolution varies between the markers, and sometimes, recovery might not occur, even after prolonged recovery. Therefore, it is important to measure the recovery status of soldiers with both biomarkers and physical performance markers, especially after strenuous training, to maximize operational capability during prolonged missions. Keywords: military operation; stress; soldiers; time to recover 1. Introduction Soldiers experience several psychophysiological stressors during military training and operations. Operative duties such as load carriage, carrying and handling heavy loads, maneuvering in difficult environments, and casualty evacuation are physically strenuous tasks [ 1 – 3 ]. In addition, the psychological demands are also high, including the possibility of death and the possible long duration of operations influencing the ability to maintain vigilance [3]. The goal of military training is to train and prepare soldiers to be resilient to high loads of physical and mental stress that are prevalent in combat situations [ 4 , 5 ]. Therefore, soldiers are frequently exposed to strenuous field training, which simulates the demands of military operations. This training includes high levels of physical activity, often accompanied by sleep deprivation and calorie restriction. As a result, fatigue may accumulate Physiologia 2023,3, 627–641. https://doi.org/10.3390/physiologia3040046 https://www.mdpi.com/journal/physiologia Physiologia 2023,3628 concurrently with physiological impairments, leading to decreased performance. The management of fatigue and recovery can be disturbed by high operational tempo, as optimal recovery might not be achieved between and during operations [3]. Intense and long-lasting training can lead to altered recovery status such as functional (FOR) or non-functional (NFOR) overreaching states [ 6 ]. In FOR, the soldier trains hard and makes an effort to accomplish supercompensation, which can lead to performance gains after a recovery period. On the other hand, in NFOR and OTS, the soldier does not have proper recovery period after hard training, and physical performance is negatively affected. FOR recovery can take from days to weeks [ 6 ]. NFOR is often seen as a cause of imbalance between the amount and intensity of training together with insufficient recovery that may lead to attenuated physical performance or other maladaptive responses. NFOR recovery typically takes from weeks to months [ 6 ]. Ultimately, this imbalance can lead to overtraining syndrome (OTS), which is characterized by decreased performance for a long period of time, and recovery can take several months [ 7 ]. In the military, NFOR, FOR, and even OTS can be developed during training and operations [8]. Recovery is a multifaceted restorative process, occurring relative to time. If psychological or physical stressors disturb recovery, fatigue may occur [ 9 ]. Fatigue can be compensated with different recovery methods, which means that the organismic balance is returned [ 10 ]. There are several methods such as physical performance tests (e.g., jumps, strength tests, and aerobic and anaerobic tests) to measure recovery status in soldiers. Additionally, biochemical markers (e.g., testosterone and cortisol), as well as heart rate variability [ 11 ], could identify the recovery level of the actual physiological status [ 12 ]. The physiology of common stress biomarkers used in military studies with operational troops was recently documented by Beckner et al. [ 13 ]. Recovery is extensively studied in athletes, but this research is not directly applicable to all military populations as athletes optimize their sleep and food intake and quality, and use other recovery methods during their training periods [ 6 ]. Within an operational military context, the extreme conditions must be endured until the mission is complete, with limited possibility to individually optimize recovery during the operative stress. If recovery is not optimal between operations, performance may be impaired when starting the next operation [ 6 , 8 ]. Therefore, knowledge about the recovery time-course after exposure to severe military training induced stress is important. The present systematic review aimed to synthesize data from studies measuring physiological biomarkers and physical performance recovery time among soldiers during and after stress induced by strenuous military training and operations. A better understanding of the physiological recovery state and performance of soldiers during and after operations may improve fatigue management. 2. Methods 2.1. Experimental Approach to the Problem The present systematic review was conducted during the first quarter of 2023 in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines [ 14 ]. The following electronic databases were used: Medline (Ovid) and Web of Science (WoS). No limits were placed on the age of the article, although articles were limited to those written in English. Boolean search was used with several military training-related words and word combinations (Figure 1). Physiologia 2023,3629 Physiologia 2023, 3, FOR PEER REVIEW 3 Figure 1. Boolean search procedure and search phrases/words and article exclusion criteria. 2.2. Procedures 2.2.1. Article Screening/Study Selection The screening of articles for potential relevance was first determined based on the title of the article, and second, on the abstract. Articles consisting of data from strenuous military training or operations/deployment and measuring metabolic, endocrinological, or physical performance factors before, during, and after strenuous military training or operations were included. Of the abstract-screened and included articles, full texts were obtained and read. 2.2.2. Quality Assessment The quantitative quality assessment tool “QualSyst” was used when assessing the methodological quality of each selected study. It includes 14 questions, which are scored from 0 (criterion not met) to 1 (criterion met partially) and 2 (criterion met fully). Items not applicable to the study design were marked as “N/A” and were not included in the calculation of the overall score [15]. The outcome score was then divided by the total possible score. A study was considered of high quality if the score was 75% or higher, moderate quality if the score was between 55% and 75%, and weak quality if the score was lower than 55%. This assessment toolkit has also been used in previous systematic reviews in a military context and in a review about overtraining syndrome in soldiers [6]. Slight modifications were made to better suit the military context: Item 3 was shortened to only include “Method of subject selection?”, item 4 was shortened to “Subject characteristics sufficiently described?”, and item 8 was shortened to “Outcome measures well defined and robust to measurement/misclassification bias? Means of assessments reported?”. Figure 1. Boolean search procedure and search phrases/words and article exclusion criteria. 2.2. Procedures 2.2.1. Article Screening/Study Selection The screening of articles for potential relevance was first determined based on the title of the article, and second, on the abstract. Articles consisting of data from strenuous military training or operations/deployment and measuring metabolic, endocrinological, or physical performance factors before, during, and after strenuous military training or operations were included. Of the abstract-screened and included articles, full texts were obtained and read. 2.2.2. Quality Assessment The quantitative quality assessment tool “QualSyst” was used when assessing the methodological quality of each selected study. It includes 14 questions, which are scored from 0 (criterion not met) to 1 (criterion met partially) and 2 (criterion met fully). Items not applicable to the study design were marked as “N/A” and were not included in the calculation of the overall score [ 15 ]. The outcome score was then divided by the total possible score. A study was considered of high quality if the score was 75% or higher, moderate quality if the score was between 55% and 75%, and weak quality if the score was lower than 55%. This assessment toolkit has also been used in previous systematic reviews in a military context and in a review about overtraining syndrome in soldiers [ 6 ]. Slight modifications were made to better suit the military context: Item 3 was shortened to only include “Method of subject selection?”, item 4 was shortened to “Subject characteristics sufficiently described?”, and item 8 was shortened to “Outcome measures well defined and robust to measurement/misclassification bias? Means of assessments reported?”. Physiologia 2023,3630 3. Results 3.1. Study Selection The literature search conducted on both databases yielded an overall number of 3681 results . Following abstract screening, 146 records were included for full-text review. Of these, 54 duplicates were removed. Thus, 92 reports were sought for retrieval (for 7 articles, the full text could not be retrieved). Therefore, 85 reports were assessed for eligibility in the full-text screening. Following the full-text screening, 12 studies were included in the review. Reasons for exclusion following the full-text screening are presented in the PRISMA flow diagram (Figure 2). Physiologia 2023, 3, FOR PEER REVIEW 4 3. Results 3.1. Study Selection The literature search conducted on both databases yielded an overall number of 3681 results. Following abstract screening, 146 records were included for full-text review. Of these, 54 duplicates were removed. Thus, 92 reports were sought for retrieval (for 7 articles, the full text could not be retrieved). Therefore, 85 reports were assessed for eligibility in the full-text screening. Following the full-text screening, 12 studies were included in the review. Reasons for exclusion following the full-text screening are presented in the PRISMA flow diagram (Figure 2). Figure 2. PRISMA flow diagram. Figure 2. PRISMA flow diagram. Physiologia 2023,3631 3.2. Characteristics of Included Studies All 12 studies included male participants (n = 7–43/study) with ages ranging from 18 to 35 years, with the most common mean age being 22–24 years. Three of these studies described the U.S. Army Ranger course, two described survival, evasion, resistance, and escape courses (SERE), and the rest described strenuous military training or selection courses. The duration of the studies ranged from 4 to 62 days, and all studies were both physically and mentally stressful due to continuous physical exertion, load carriage, sleep deprivation, and energy deficit. Participant details, description of training, and measurement outcomes of the included studies are presented in Tables 1and 2. 3.3. Measured Outcomes The physical performance of the soldiers was measured in 5 studies, and biomarkers in 11 studies. The methodological measures of physical performance and biomarkers varied widely between the studies. Common physical performance assessments included different types of strength tests in five studies. Endurance performance (aerobic or anaerobic) was measured in two studies. A variety of blood biomarkers consisting of hormones, muscle damage and inflammatory as well as oxidative stress markers (Table 2) were measured. A total of 61 different biomarkers were measured across the studies. The most commonly measured biomarkers were basic stress-related outcome markers, such as testosterone (n = 8) and cortisol (n = 6). 3.4. Recovery Assessments The recovery status of soldiers was assessed for no longer than 2 weeks in 8 studies, and in 4 studies, recovery was followed for 2–6 weeks. The majority of studies included multiple recovery measurements over different time points. One study assessed recovery for all parameters only after 24 h [ 16 ]. For two studies, recovery was assessed at only the time point of 30 [ 17 ] or 35 days [ 18 ]. In two studies, the post-measurements were not performed directly after the course but at 8 h [ 19 ] and 2 weeks [ 20 ] after the end of the course. Two other studies measured adverse changes during and after the course [ 16 , 21 ]. The remaining studies performed the post-measurements immediately after the course. Table 1. Participant details and description of training. Study Participants Type of Training Description of Training Energy Expenditure or Deficit/Amount of Food Provided Sleep Mourtakos et al., 2021 [17] n = 14, age 22.7 ±1.7 yr, male Greek Special Forces volunteers “Hell Week” of Basic Underwater Demolition(s) (BUD/S) of the Hellenic Navy SEALs 5-day “Hell Week” of the 32 week “brutal” BUD/s schedule. During “Hell Week”, candidates participate in training course characterized by extreme mental and physical fatigue, e.g., walking 300 km and performing physical training for more than 20 h per day in harsh conditions. Not reported No sleep at all during the entire week Conkright et al., 2020 [20] n = 10, age 24.0 ±5.0, active-duty male U.S. Army 75th Ranger Regiment soldiers Ranger course 62-day length, one of the military’s most challenging courses. Training small unit tactics and leadership under conditions of severe stress created by sleep and caloric restriction, physical exertion, and graded evaluations. Approx. 20 h of training per day, 7 days a week, with 30–40 kg extra weight to carry. Energy deficit approx. 1200 kcal per day, on average Less than 4 h per night Vikmoen et al., 2020 [22] n = 23 men, age 19.3 ± 1.8 yr, Norwegian conscripts who completed a selection exercise Armed Forces Special Command, Parachute Ranger Platoon selection Selection exercise; extremely demanding field exercise that lasts ~5 and half days. Designed to test physical and mental resilience in extreme situations in sub-optimal conditions. Consisted of large amounts of physical activity in addition to sleep and food restriction. Main activities: loaded marching and various mentally and physically challenging tasks. Carried load varied between 20 and 40 kg during exercise. Energy expenditure estimated at 7235 ±408 kcal/day. Food intake was 575 kcal/day, except for day 3, when it was 3755 kcal. 1–6 h/day Physiologia 2023,3632 Table 1. Cont. Study Participants Type of Training Description of Training Energy Expenditure or Deficit/Amount of Food Provided Sleep Hamarsland et al., 2018 [19] n = 15, aged over 18, apprentices applying for Norwegian Naval Special forces First 6 weeks of Naval Special Forces selection course First 3 weeks: military camp with heavy physical activity and sleep restriction in a stressful environment; week 4: “hell week”, consisting of sleep and calorie restriction and extreme amounts of physical activity for 20 h per day in a very stressful and difficult environment with about 35 kg of carried load. Weeks 5–6: recovery. First 3 weeks food intake: ad libitum. Hell week: 10,000 kcal combat ration provided at the start, for the whole week First 3 weeks: not stated. Hell week: 2–3 h of sleep per night Kyröläinen et al., 2008 [23] n = 7, Finnish male soldiers, age 24 ±2 years Prolonged military field exercise 20-day field exercise, three phases: First 7 days: Phase 1, very heavy, consisting of walking 20–25 km per day in the forest carrying approx. 50 kg of gear. Six days of phase 2: Easy, walking 5–10 km per day with 20–25 kg of gear. Last week phase 3: heavy, approx. 15 km per day with 30 kg of gear. Daily energy intake average: 2938 ±454 kcal/day, with no differences between different phases. Energy deficits were 4000, 450 and 1000 kcal/day in P1 (~7000 kcal EE), P2 (~3200 kcal EE) and P3 (3500 kcal EE). Average of 6 h sleep per night during the whole field exercise Santos et al., 2018 [21] n = 43, age 18–23, Brazilian 1st Command Action Battalion male soldiers Army Corporal Training Course, Combat Simulation exercise A total of 4 full days of 24 h continuous operations; evaluation of leadership potential in combat. Included 25 kg of added weight + other material to carry. R2 ration includes 3000–3600 kcal of energy. Day 1: full R2 ration, Day 2: 1/2 R2 ration, Day 3: 1/3 R2 Ration, Day 4: - Day 1: 2 h, Day 2: 2 h, Day 3: 1 h, Day 4: - Szivak et al., 2018 [8] n = 20, age 18–35, active-duty men serving in the U.S. Navy and Marine Corps Navy SERE course Highly classified. ~2 weeks of highly realistic SERE training including multiple stressors: environmental extremes, physical demands, food and sleep deprivation, psychological stress. First 4 days was didactic phase, followed by field training phases: Evasion phase: several days of practicing evasion techniques in difficult terrain. Capture phase: several high-stress training scenarios of realistic captivity experience. Several days of food restriction Several days of sleep deprivation Henning et al., 2013 [24] N = 23, age 23.0 ±2.8 U.S. Army 2/75th Ranger Regiment male soldiers who completed Ranger Training without recycling Ranger Training Course 61 days, 30–40 kg load carry, over 200 miles of movement during the course, and food and sleep deprivation. Same course as Conkright et al., 2018. [20] 2200 kcal of food provided per day 0–5 h of sleep per night Nindl et al., 1997 [18] n = 10, U.S. male soldiers from Army Ranger Training Course Army Ranger Course Demanding 62-day training program designed to teach and evaluate leadership and small unit tactics under physically and mentally challenging conditions. Multi-stressor environment, 20 h of training each day in forest, forested mountains, coastal swamp, and desert Estimated energy expenditure: 4200 kcal/day. Caloric intake: 3200 kcal/day. A deficit of 1000 kcal/day Description indicates maximum of 4 h per night; might be lower Gunga et al., 1996 [25] n = 29, age 22.2 ±2.8, male members of Austrian Army special forces training unit Survival training course 5-day survival training; 430–570 m above sea level in a wooded area. Incl. 90 km marching, tactical missions with 22.3 kg weight. 1st day breakfast of 1500 kcal; after that, mean energy intake was 150 kcal/day. Water was limited to 1 L/day (+1 L 1st day morning and 4th day afternoon) Overall, 20 h of sleep over 5 days (no tent and no sleeping bag) Opstad, 1994 [26] n = 10, age 22–26, male cadets of the Norwegian Military Academy Military training course 5 days continuous physical exercise (infantry activities) around the clock in a forest area at a 500 m altitude Energy expenditure of 40,000 kj/24 h (9560 kcal); energy intake 5000 kj/24 h (1195 kcal) No organized sleep, some minutes between activities, total 1–3 h during the whole course. Opstad, 1982 [27] n = 11, two groups (iso-calorie: n = 5, age 22.9. low-calorie: n = 6, age 22.8). Norwegian Military Academy male cadets Norwegian Military Ranger training course 5-day ranger training course with continuous and heavy activities Energy expenditure of 8000–11,000 kcal/day. Low-calorie group intake was 1500 kcal; deficit 7000–10,000 kcal. Iso-calorie group intake was 6400 kcal/day Less than 2 h of total sleep during the course Physiologia 2023,3633 3.5. Quality Assessment According to the “QualSyst” checklist, seven studies were rated as “moderate” quality and five as “weak”. Supplementary Table S1 presents the critical appraisal of the studies. The studies scored 10 to 15 “QualSyst” points. Despite the low sample sizes, substantial outcomes were observed for the majority of the main variables. Nevertheless, considerably low sample sizes still accommodate bias, which is especially relevant in hormonal measurements with wide measurement ranges. In addition, variances were rarely reported for the main outcomes, which lowered the overall scores for all except four studies. In addition, mainly due to the nature of field experiments, the study designs tended to lack appropriateness to be rated a full two points. 3.6. The Effects of Training Courses on Physical Performance Statistically significant decreases in physical performance were observed after the training course (ranging from 6 to 62 days) in four out of five studies [ 1 , 18 – 20 ], except the study by Szivak et al. [ 16 ]. In these studies, all the measured physical performance outcomes declined, apart from the study by Conkright et al. [ 20 ], in which all other performance measures, except deadlift repetition strength with 225 lbs and bench press repetition strength with 185 lbs, decreased after the course. 3.7. Recovery of Physical Performance Among studies reporting decrements in physical performance with a recovery followup, Nindl et al. [ 18 ] was the only one to report the recovery of all outcomes (muscle strength measured as machine simulating power clean, vertical jump height, and explosive power), occurring after 5 weeks. In the other studies, recovery occurred only for some outcomes. Conkright et al. [ 20 ] reported that only push-ups and pull-ups returned to baseline after 6 weeks of recovery following a 62-day Ranger course, while other measures (speed/mobility, anaerobic capacity, aerobic fitness) remained non-recovered. Hamarsland et al. [ 19 ] reported no clear signs of recovery 72 h after the 6 weeks of the Naval Special Forces selection course. Chest press recovered after 1 week and leg press after 2 weeks, but counter-movement jump (CMJ) remained depressed after 2 weeks. Follow-up from a five-and-a-half-day selection exercise to Special Forces reported that upper body power recovered after 1 week and anaerobic performance measured by an evacuation test recovered after two weeks, but CMJ still remained decreased after two weeks [ 22 ]. These results are summarized in Supplementary Table S2. Table 2. Measurement times, main outcomes, main findings, and recovery. Study When Testing Was Conducted What (Relevant) Markers Were Measured Main Findings Recovery of Markers? Mourtakos et al., 2021 [17] Baseline (BL): 7 days prior to “Hell Week”. During: on each of the 5 days of “Hell Week”. Recovery: 30 days after completion. Plasma protein concentration, plasma heat capacity profiles, albumin and globulin peak enthalpies and temperatures The main finding was that the thermal stability of plasma albumin was enhanced and denaturational transition to higher temperatures shifted. The major effect of exercise was a continuous upward shift in the albumin peak by 2–3 Celsius, tending to plateau on the 5th day. Some redistribution of the denaturational enthalpy was also observed during exercise: globulin peak increased relative to albumin peak, especially during first 4 days. Total recovery to the initial signature pattern after 30 days’ recovery. Yes. Conkright et al., 2020 [20] Baseline (BL) pre-Ranger School, two-weeks post (P1)-, and six-weeks post (P2)-Ranger School Physical performance with modified Ranger Athlete Warrior assessment. Speed and mobility: Illinois Agility Test (IAT) test, muscular endurance (push): metronome push-up, muscular strength/endurance (pull): overhand pull-up, core strength: heel clap, anaerobic capacity: 300 yd shuttle run, aerobic fitness 20 m multistage beep test. Strength: 185 lbs bench press and 225 lbs deadlift rep max. Significant declines across time points in all performance measures except deadlift and bench. BL to P1 declines: push-ups ↓~24%, pull-ups ↓~28%, heel claps ↓~35%, IAT ↓~9%, beep test ↓~20%. The 300 yd run did not decline at P1, only at P2. Push-up and pull-up returned to BL by P2. Other measures related to speed/mobility, anaerobic capacity, and aerobic fitness remained under-recovered at P2 related to BL: IAT ↓~15% and 300-yard run ↓~7% slower, heel clap ↓~27% decline, beep test ↓~23% decline related to BL. Partial. Push-up and pull-up recovered to BL after 6 weeks; other variables did not. Physiologia 2023,3634 Table 2. Cont. Study When Testing Was Conducted What (Relevant) Markers Were Measured Main Findings Recovery of Markers? Vikmoen et al., 2020 [22] Baseline (BL) and 0 h (only physical perf), 24 h (physical perf + blood), 1, 3, 7, and 14 days after field exercise. Blood: Cortisol (COR), testosterone (T), creatine kinase (CK), insulin-like growth factor 1 (IGF-1). Physical performance: counter-movement jump (CMJ) (n = 17), medicine ball throw (MBT) (n = 18), evacuation test for anaerobic performance (EVAC) (n = 18). Physical performance: CMJ height decreased after the exercise (↓7.5 cm) and was still ↓6.6 cm reduced after two weeks recovery. CMJ max power followed a similar pattern. EVAC test times were about 50% slower after exercise, with recovery to BL after 2 weeks. MBT: ↓0.5 m; back to BL after 1 week of recovery. Blood: T ↓58% 24 h after the exercise. Still ↓20% at 72 h rec. Increase compared to BL after 1 (↑87%) and 2 weeks of (↑113%) recovery. COR: Increase during exercise (↑26%); back to BL after 72 h of recovery. IGF-1: decrease during exercise; was ↓28% lower at post. After that, IGF-1 increased gradually, and levels were higher than BL after one week of recovery. CK was increased significantly 24 h after exercise (↑353 ±430%), back to pre-values after 72 h of recovery, and decreased to below prevalues after 1 wk and 2 wk of recovery (↑85%). Partial. Blood biomarkers recovered after 1 week. CMJ did not recover at 2 weeks, MBT recovered after 1 wk and EVAC after 2 wk. Hamarsland et al., 2018 [19] Baseline (BL): day 2 of 1st week and Pre: day before hell week (HW). Post: Blood samples immediately after termination of hell week; physical performance 8 h later. Recovery: all measures after 24 h, 72 h, 1 wk, and phys perf 2 wk. Physical performance: counter-movement jump (CMJ), isometric leg press, isometric chest press. Blood samples: T, COR, T/C ratio, sex hormone-binding globulin (SHBG), CK, C-reactive protein (CRP), thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), T3/T4 ratio, IGF-1 and insulin-like growth factor-binding protein 3 (IGFBP-3). Free testosterone (FT) was calculated. After HW: Physical performance at post: CMJ ↓28%, leg press ↓20%, chest press ↓10%. No clear signs of recovery after 72 h. One week after, chest press returned to prelevels. Leg press recovered after 2 wk, CMJ still depressed after 2 wk (↓14%). T pre–post ↓70%; after 1 wk, returned to normal. FT ↓39% at post-, ↓60% after 24 h, ↓50% at 72 h, and normal after 1 wk. SHBG pre–post ↑24%, still elevated at 72 h, normalized after 1 wk. COR ↑154% at post-, elevated after 1 wk (↑43%). T/C ratio ↓87% at post-, ↓63% at 24 h, ↓58% at 72 h, back to baseline after 1 wk. IGF-1 and IGFBP-3 both ↓(45/37%) at post-, gradual rec and normalized after 1 wk. T3 and T4 ↓(32%/12%) at post-, gradual recovery to prewithin 1 wk. T3/T4 ratio ↓77% at post-, gradual recovery toward prewithin 1 wk. TSH significantly increased (↑58%) only after 1 wk. CK elevated at post- (700%), decreased to below prevalues after 1 wk. CRP ↑1300% at post-, ↑1500% at 24 h, and below prevalues within 1 wk. Partial. Some hormones normalized after 1 wk; some did not. Recovery of chest press after 1 wk, leg press after 2 wk. CMJ still depressed after 2 weeks Kyröläinen et al., 2008 [23] Pre/BL: one day before start, days 5 (P-1mid), 8 (P-2pre), 14 (P-3pre), 16 (P-3mid) and 21 (P-3post) (NOTE = Only first 7 days were considered as the “intervention”. All else were recovery) Blood: COR, growth hormone (GH), glucose (GLU), CK, urea (U), T, FT, T4, follicle-stimulating hormone (FSH), luteinizing hormone (LH), insulin (INS), Plasma volume (PV) (limited data on plasma volume to assess recovery). Blood GLU not changed by day 5, ↓13,3% at the end of P-1 (day 7). Back to BL on day 8. At P1-mid (5 days), COR ↑32%, GH ↑616% and INS ↓70%. After these initial rises, COR and GH returned to BL at P-2pre, and INS at the end of P-3post. At P1-mid, T ↓27%, FT ↓26% and LH ↓46%; no change in FSH. All these returned to BL by P-3pre. Serum T4 p1mid ↓9% non-significant, was lower and urea concentration was higher after the whole exercise than BL. No changes in T4 and urea during the first part of the exercise. PV changed slightly during the course. CK increased at P-1mid ↑555% and returned to BL on day 16. Yes, except T4 was lower and urea concentration was higher after the exercise. Santos et al., 2018 [21] BL/T0 before beginning of activities (fasted), T1 at 72 h after baseline after 100 km march, and T2 at 63 h after the end of military activity Blood samples: CK, myoglobin (MB), CRP, alpha 1-acid glycoprotein (AGPA), lactate dehydrogenase (LDH), lactate CK ↑1035% at T1; returned to baseline at T2. LDH: ↑122% at T1; still ↑37% increased at T2. Lactate ↑127% at T1; returned to baseline at T2. MB: ↑728% at T1; returned to baseline at T2. CRP: ↑182% at T1; returned to baseline at T2. AGPA: ↑14.7% at T1; returned to baseline at T2. Thus, markers increased significantly at T1 and returned to levels close to baseline at T0, except LDH, which did not. Yes, except one marker (LDH); marker recovery occurred after 63 h Szivak et al., 2018 [16] (BL)/T1, first day of SERE. Stress assessment (T2), 10 d after T1. Recovery assessment (T3), 24 h after T2. Blood samples: Epinephrine, norepinephrine, dopamine, COR, T, and neuropeptide-y (NPY) at all testing points. Physical performance: vertical jump, dominant handgrip, nondominant handgrip at test points T1 and T2, and no recovery measure. Physical performance did not decrease from T1 to T2. Exposure to stress resulted in significant increases in plasma epinephrine ↑70%, plasma norepinephrine ↑191%, plasma dopamine ↑186% and serum COR concentration ↑525%, and a reduction in TES concentrations ↓63%. No significant elevations in plasma NPY. However, NPY decreased significantly at T3 (↓56%). Of the markers that showed increase at T2, only epinephrine recovered at T3; others were still elevated from BL values after 24 h (Norep ↑82%, Dop ↑79% COR ↑172%, Test ↓54%). No. Of the affected markers, only epinephrine levels recovered after 24 h. Henning et al., 2013 [24] Before (BL) and immediately after (Post) Army Ranger course. Recovery measures after 2–6 weeks. Note = n = 23 at BL and post-; n = 9 on the recovery measures (no R.D. = no recovery data). Blood samples: COR (no R.D.), T3, T4 (no R.D.), TSH (no R.D.), dehydroepiandrosterone-sulfate (DHEA-S) (no R.D.), brain-derived neurotrophic factor (BDNF), total and free IGF-1, IGFBP-1 (no R.D. On 2–6), Cytokines (INF-y (no R.D.), IL-1 (no R.D.), IL-4, IL-6, IL-8, IL-10 (no R.D.), TNF-alpha (no R.D.), CRP (no R.D.)), T, SHBG. T decreased ↓70% at post. Serum SHBG ↑46% at post. COR nonsignificant increase, DHEA-S no change at post. BDNF ↑33% at post. T3 showed a trend to decrease (↓8%) at post. TSH ↑85% at post. No change in T4 at post. Total IGF-1 decreased ↓38.7% and free IGF-1 ↓41% at post. IGFBP-1 ↑534.4%, IGFBP-2 ↑98.3% and IGFBP-3 ↑14.7% at post. IGFBP-6 ↓23.4% at post. Il-4 ↑135.3%, IL-6 ↑217.2%, and IL-8 ↑101,.4%. No changes in INF-y, IL-1B, Il-10, TNF-alpha or CRP. After 2–6 weeks, all markers with recovery data recovered to BL concentrations except T3 (↑17%). All markers with recovery data recovered to BL after 2–6 weeks, except T3 elevated. Physiologia 2023,3641 26. Opstad, K. Circadian rhythm of hormones is extinguished during prolonged physical stress, sleep and energy deficiency in young men. Eur. J. Endocrinol. 1994,131, 56–66. [CrossRef] [PubMed] 27. Opstad, P.K.; Aakvaag, A. Decreased serum levels of oestradiol, testosterone and prolactin during prolonged physical strain and sleep deprivation, and the influence of a high calorie diet. Eur. J. Appl. Physiol. Occup. Physiol. 1982 ,49, 343–348. [CrossRef] [PubMed] 28. Opstad, P.K. The hypothalamo-pituitary regulation of androgen secretion in young men after prolonged physical stress combined with energy and sleep deprivation. Acta Endocrinol. 1992,127, 231–236. [CrossRef] [PubMed] 29. Church, D.D.; Gwin, J.A.; Wolfe, R.R.; Pasiakos, S.M.; Ferrando, A.A. Mitigation of muscle loss in stressed physiology: Military relevance. Nutrients 2019,11, 1703. [CrossRef] [PubMed] 30. Trousselard, M.; Cian, C.; Barraud, P.-A.; Ferhani, O.; Roux, A.; Claverie, D.; Canini, F.; Baert, P. Physiological and psychological effects of escape from a sunken submarine on shore and at sea. Aviat. Space Environ. Med. 2009,80, 850–856. [CrossRef] Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). 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