Challenges in Conducting Exercise Recovery Studies in Older Adults and Considerations for Future Research: Findings from a Nutritional Intervention Study

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have presented a very candid summary of the challenges they had with recruitment, and also the potential issues with the exercise protocol for this specific intervention study. They have sensibly not conducted any inferential statistics, and provided a number of recommendations for future research, which is where the usefulness of this article lies. Despite this, there are some updates which need to be made before this paper can be considered for publication:

 

Introduction

Lines 30-31: I feel that a suitable reference would be appropriate here to support this statement.

 

Methods

Line 89-90: What software program was used to conduct the randomisation? What thresholds were used to stratify participants regarding MIVC?

 

Lines 113-114: Was this a validated food diary, or was it an ‘in-house’ version? Please clarify. Also, you state this was used for “…analysis and comparison between groups.” It is not totally clear how you do this, so please expand further.

 

Lines 125-127: Were you aiming for any particular level on the Borg scale? Please clarify.

 

Line 147 and 173: Any previously published literature to back-up the methods used?

 

Results

Line 213: It is a shame that recruitment did not go to plan for this study. Although I appreciate inferential statistics would not be appropriate, is it possible to compare your findings with MCIDs for adults or older adults? I would suspect these might be available for the TUG and five chair stands test.

 

Discussion

Line 268: Use another word to replace “significant”.

 

References

Some of the references used the full journal title, instead of the abbreviated version (e.g. American Journal of Medicine, Clinical Biomechanics). Please update this list accordingly.

Author Response

We thank you very much for taking the time to review our manuscript. Please find our responses to your comments below alongside a tracked changes document with the updated manuscript.

 

Introduction

Lines 30-31: I feel that a suitable reference would be appropriate here to support this statement.

• Thank you for your comment. Reference now included on Line 31.

 

Methods

Line 89-90: What software program was used to conduct the randomisation? What thresholds were used to stratify participants regarding MIVC?

• Thank you for your comment. Due to the small number of participants no software was used for the randomisation. We have included the following text to further clarify the allocation process:
• [“Participants were randomly stratified based on sex and maximal isometric voluntary contraction (MIVC) of the knee extensor as blocking factors using co-variate adaptive randomisation [16]. MIVC stratification thresholds were ≤100 Nm, 100 – 150 Nm, and >150 Nm.”] (L98-100)

 

Lines 113-114: Was this a validated food diary, or was it an ‘in-house’ version? Please clarify. Also, you state this was used for “…analysis and comparison between groups.” It is not totally clear how you do this, so please expand further.

• Thank you for picking up on this. This study used a standard weighed food diary on a paper template given to participants. This is an ‘in-house’ template, we are unaware of any directly validated templates for weighed food diaries. We have given further clarification of how food diaries were analysed [“Participants were given a paper template to record their food and drink intake in a weighed food diary for the 24-hours prior to the first experimental visit. This was analysed for total energy and macronutrient intake to ensure diet was not significantly different between groups at baseline.”](L122-125)

 

Lines 125-127: Were you aiming for any particular level on the Borg scale? Please clarify.

• Thank you for your comment. We were not aiming for a particular number on the Borg scale due to ratings of perceived exertion (RPE) being highly variable and difficult to predict. However, as this was targeted to be a ‘usual’ training session, we would expect RPE to be in the range of ‘somewhat hard’ to ‘very hard’. We were satisfied that each group perceived similar exertion during the exercise protocol, and that all exercises were deemed at least ‘somewhat hard’. For continuity and illustrative purposes, we have now included the average RPE across exercises within Table 2 (L244)

 

Line 147 and 173: Any previously published literature to back-up the methods used?

 

• Yes, for postual stability the following text has been included [“Currently, only one study has investigated the effects of resistance exercise on postural control in the 72-hours following exercise in older adults [4,17]. Using a similar methodology to the previous study [17], postural stability was quantified by the assessment of Centre of Pressure (COP) sway.”] (L187-189)
• For MIVC a reference has now been provided to a review which details all studies using a similar protocol (L178).

 

Results

Line 213: It is a shame that recruitment did not go to plan for this study. Although I appreciate inferential statistics would not be appropriate, is it possible to compare your findings with MCIDs for adults or older adults? I would suspect these might be available for the TUG and five chair stands test.

• Thank you for this suggestion. Whilst the authors appreciate that MCID is important for clinical populations we do not feel that reporting MCIDs from other studies is suitable in this instance. This is because MCID is influenced by several factors including study population and trial design which are specific to the calculation of each MCID value. We do not feel that there is a suitable MCID value for TUG or 5-CS which would accurately reflect the current study. This article provides further clarification on this topic (PMID: 35210873).
• We have however included a more direct comparison of the change in time to complete the TUG test in our study to a similar study assessing the repeatability of the TUG test. We have also reported the normative values of TUG for those ages 70-79 y alongside the absolute values of the two other studies reporting TUG following resistance exercise to provide more context to our results. [“Baseline values of TUG speed (~ 8 s) in the present study are not likely to be a reason for this difference, with the previous studies reporting similar baseline speeds of 6 to 11 s [18,35], and the normative value for TUG being 9.2 s in 70 -79 year olds [36].”] (L291-301)

 

Discussion

Line 268: Use another word to replace “significant”.

• Thank you for your comment. We have replaced the word ‘significant’ with the word ‘substantial’. (L296)

 

References

Some of the references used the full journal title, instead of the abbreviated version (e.g. American Journal of Medicine, Clinical Biomechanics). Please update this list accordingly.

• We have attempted to change reference styles in order to abbreviate the journal titles several times using Mendeley to no avail. Would the editorial office please be able to advise the correct abbreviation of the journal titles so that this can be edited manually? Alternatively, would it be possible to advise if there is a way to change journal abbreviation rules within reference styles on Mendeley?

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript explores the challenges faced in conducting exercise recovery studies in older adults, drawing from a specific nutritional intervention study investigating the effects of milk consumption on recovery from resistance exercise (RE). While the study is well-conceived, several major issues need addressing to enhance the manuscript's clarity, robustness, and contribution to the field.

Major issues
- The study recruited only 11 participants, falling significantly short of the 36 required to achieve statistical power. Clearly state the implications of the underpowered study on the validity and generalizability of the findings. Consider conducting a more comprehensive discussion on how future studies could mitigate these recruitment challenges.

- The study acknowledges potential learning effects due to inadequate familiarization with the RE and outcome measure. Include a plan for addressing learning effects in future studies. This might involve increasing the number of familiarization sessions and ensuring participants reach a performance plateau before the intervention begins.

- The manuscript questions the validity of certain outcome measures (e.g., TUG, five chair stands, COP sway) for detecting exercise-induced muscle damage in older adults. Propose a strategy for validating these measures specifically for older adults. This could involve a pilot study or referencing existing literature where these measures have been validated in similar populations.

- The chosen exercise protocol may not have been sufficiently intense to cause measurable muscle damage. Clarify the rationale for the chosen exercise intensity and provide a comparative analysis with protocols known to induce muscle damage. Suggest adjustments or alternative protocols that could reliably induce muscle damage in older adults.

- Recruitment was limited, and several potential participants were excluded due to the strict inclusion criteria. Discuss alternative recruitment strategies and broader inclusion criteria that could enhance participant enrollment without compromising safety. Consider collaborating with more institutions or using more diverse recruitment channels.

- The study used milk as the nutritional intervention, but participant adherence and perceptions were not thoroughly explored. Provide more details on participant adherence to the nutritional intervention and discuss any feedback received from participants. This could offer insights into the acceptability and practicality of milk as a recovery aid. Furthermore, please address potential issues related with lactose malabsorption and intolerance in older adults and implications for what concerns extending this approach to general population.

- The results section is brief and lacks detailed statistical analysis due to the small sample size. Expand the results section with more descriptive statistics and exploratory analyses, even if they are not statistically significant. This will provide a fuller picture of the data trends and variability.

 

- The discussion section could benefit from a more detailed exploration of the implications of the findings for future research. Enhance the discussion by integrating findings with broader literature on exercise recovery in older adults. Highlight how the study's insights can inform future research design, participant engagement, and intervention strategies.

 

Minor issues

- Ensure consistency in formatting, particularly in tables and figures.

 

- Improve the manuscript's readability by simplifying complex sentences and avoiding jargon where possible.

Comments on the Quality of English Language

- Improve the manuscript's readability by simplifying complex sentences and avoiding jargon where possible.

Author Response

We thank you very much for taking the time to review our manuscript. Please find our responses to your comments below alongside a tracked changes document with the updated manuscript.

 

The study recruited only 11 participants, falling significantly short of the 36 required to achieve statistical power. Clearly state the implications of the underpowered study on the validity and generalizability of the findings. Consider conducting a more comprehensive discussion on how future studies could mitigate these recruitment challenges.

• Thank you for your comment, we have included the following reminder on the generalizability of the findings [“and hence, all results should be interpreted with caution, and no conclusions should be drawn as to the effectiveness of whole milk as an exercise recovery supplement”](L62-64)
• Thank you for your comment. We have added to the discussion regarding mitigation of recruitment challenges. [“At present, it is unclear how these obstacles to recruitment could be overcome for such a study, given that these issues are integral to the study design. It is possible that similar studies may have to plan for a longer recruitment period in lieu of altering recruitment rate, or work collaboratively with other research centres to reach a wider population of people in order to achieve sufficient statistical power”](L264-268).

The study acknowledges potential learning effects due to inadequate familiarization with the RE and outcome measure. Include a plan for addressing learning effects in future studies. This might involve increasing the number of familiarization sessions and ensuring participants reach a performance plateau before the intervention begins.

• Thank you for your comment. Learning effects are addressed within the familiarisation section [“Learning effects are common when assessing maximal strength. As previously discussed, they are an outcome of systematic bias [34], and are moderated through familiarisation before experimental visits [40,41]. In younger adults, repeated repetitions of MIVC are generally recommended before a plateau is achieved in peak MIVC values [42], but the number of familiarisation visits required for older adults is unclear [41,43].”](L305-310) And [“If additional visits are required for familiarisation of MIVC measures in older adults, the practicability of this should be examined given that recruitment for this study was already difficult due to participant burden. Indeed, the addition of extra familiarisation visits would make future studies more methodologically rigorous but could discourage participation further.”](L317-321).
• Considerations for minimising learning effects can also be found in table 4 (L389).

The manuscript questions the validity of certain outcome measures (e.g., TUG, five chair stands, COP sway) for detecting exercise-induced muscle damage in older adults. Propose a strategy for validating these measures specifically for older adults. This could involve a pilot study or referencing existing literature where these measures have been validated in similar populations.

• Thank you for your comment, a proposal of future research to address the validity of population specific outcome measures can be found in table 4 - [“Research is needed to validate population specific outcome measures for exercise recovery in older adults”] and [“If outcome measures have been validated for other populations, consider if any adjustments need to be made (e.g., a more detailed explanation of muscle soreness may be required before assessment in older adults)”](L389).
• Furthermore, where possible existing literature for each measure has been discussed [“For example, although centre of pressure (CoP) sway has been used in one study in older adults [19] who saw a 45 % increase in CoP sway, it is not a well-used marker for exercise-induced muscle damage and future studies may wish to validate its use for this purpose.”](L336-368) and [“The expectation would be for individuals to take more time to complete the [TUG] test if muscle damage were present, as previous studies have shown a 2-18 % [19,36] peak increase in time to complete the test”](L289-291).

 

The chosen exercise protocol may not have been sufficiently intense to cause measurable muscle damage. Clarify the rationale for the chosen exercise intensity and provide a comparative analysis with protocols known to induce muscle damage. Suggest adjustments or alternative protocols that could reliably induce muscle damage in older adults.

• Thank you for your comment. The rationale for the exercise intensity can be found within the methods section [“In an attempt to replicate a pragmatic RE session to ensure ecological validity, the participants performed four sets of ten repetitions at 70% 1-RM of three lower limb exercises; leg press, knee extensions, and hamstring curls”](L127-129), and [“This is similar to the exercise protocol recommended by a meta-analysis seeking the most effective RE protocol for older adults [18], and to the protocol used by the singular recovery intervention study in older adults [19] but used larger muscle groups of the lower limbs and was altered after pilot testing to reflect what researchers thought was attainable using our specific equipment.”](L132-137).
• We also thank you for your suggestion to compare and suggest adjustments to the exercise protocols. We feel we have already suggested alternatives within the ‘Optimising exercise protocols’ section, for example: [“The exercise protocols used in these previous studies include 3 sets to failure of 95% 5-RM of leg press and leg curl [36] and 5 sets of 15 reps of back squat at 75% 1-RM [49].”](L362-364) and [“Other studies [36,50] in older adults have previously completed sets of exercises to failure to ensure all participants reach volitional exhaustion and use this as a bench-mark to standardise relative load across the population. This may be a good solution for further work, but would require an estimation of 1-RM and would likely be subject to an individual’s motivation to exercise.”](L380-384) alongside a summary of considerations for choosing exercise protocols within Table 4.(L389)
• As discussed in the paper, choosing an exercise intensity/protocol is more nuanced than us providing an alternative protocol as this will depend on the aims of any future studies (not all will be the same!). We feel the above discussion of exercise protocols known to cause damage should be sufficient to address this comment.

 

Recruitment was limited, and several potential participants were excluded due to the strict inclusion criteria. Discuss alternative recruitment strategies and broader inclusion criteria that could enhance participant enrollment without compromising safety. Consider collaborating with more institutions or using more diverse recruitment channels.

• This is similar to comment 1 and we therefore refer the reviewer to our above response. To be more specific, alternative recruitment is discussed in table 4 (L389), including collaborating with other institutions.

 

The study used milk as the nutritional intervention, but participant adherence and perceptions were not thoroughly explored. Provide more details on participant adherence to the nutritional intervention and discuss any feedback received from participants. This could offer insights into the acceptability and practicality of milk as a recovery aid. Furthermore, please address potential issues related with lactose malabsorption and intolerance in older adults and implications for what concerns extending this approach to general population.

• Thank you for your comment. Participants reported full adherence, and this has now been included in the manuscript [“Participants reported full adherence to the nutritional intervention.”](L230-231).
• For the acceptability and practicality of milk as a recovery aid, please see our previous work that explores this topic in 291 older adults (Hayes et al. 2021 )https://doi.org/10.3389/fnut.2021.748882), which is also referenced within the introduction alongside two other papers 10.1177/2333721420920398 and 10.1371/journal.pone.0235952 )(references 10-12 L55)
• Similarly, regarding the hesitancy due to allergy/intolerance, within our previous study we found only 17/291 (5.8 %) of our respondents expressed such concerns. This intervention is not designed to be ‘fix all’ and like many exercise interventions it will not be suitable for everybody and is not intended to be so. Rather, as a nutritional intervention it would act as another ‘tool in the armoury’ for improving exercise recovery.
• As an authorship team we would prefer not to discuss the acceptability of the intervention in too much detail as this paper is not so much about the nutritional intervention but on challenges of the methodology, and we do not want to detract from main message of paper.

 

The results section is brief and lacks detailed statistical analysis due to the small sample size. Expand the results section with more descriptive statistics and exploratory analyses, even if they are not statistically significant. This will provide a fuller picture of the data trends and variability.

• Thank you for your comment. As an author team we felt it bad practice to present analyses on data that we knew was not of sufficient statistical power and we note also the comment of another reviewer supporting the omission of inferential statistics. We felt that keeping data separated by group was not helpful for the messaging of the paper which focusses on lessons learnt from methodology rather than incidental statistical findings. The data submitted provides an overview of changes at each time point including the variability as SD for the whole cohort. However, we have included our exploratory analysis as supplementary material that can be included at the editors’ discretion.

 

The discussion section could benefit from a more detailed exploration of the implications of the findings for future research. Enhance the discussion by integrating findings with broader literature on exercise recovery in older adults. Highlight how the study's insights can inform future research design, participant engagement, and intervention strategies.

• Thank you for your comment. We have made several changes below.
• L237-239 [‘Recovery from resistance exercise in older adults is an emerging and important consideration in exercise sciences, but literature surrounding the topic is limited and inconsistent [4]. This was the first study which attempted to investigate the effectiveness of a nutritional intervention for improving exercise recovery’] – this provided added context that this is an emerging area of research for which little is known
• L272-275 we added the following to provide more context on the uncertainty of muscle strength response following RE in older adults [“In older adults this temporal pattern is not as well established within the literature due to differing exercise protocols and outcome measures [4]. Within current studies, it is estimated that muscular strength of the lower limbs could be decreased by 9-36 % following resistance exercise.”]
• L326-331 as above we have added the following to provide more context on what has already been investigated in older adults [“Previously only two studies have previously reported on the effects of RE on TUG performance [20,36], two studies have reported postural stability (COP sway)[2,20], and one has reported five chair stands [47]. One study has investigated chair ascent and descent performance following RE in older adults, but this was not viable to measure in the current study [36].”]
• L399-402 [“These insights should be used to inform future research design to ensure studies are methodologically robust, and sufficiently powered to detect exercise-induced muscle damage in older adults.”]

 

Minor issues

- Ensure consistency in formatting, particularly in tables and figures.

• Thank you for your comment. We have bolded text in first column of table 1 to be consistent with table 2 and 3

 

- Improve the manuscript's readability by simplifying complex sentences and avoiding jargon where possible.

• L41 we have changed [“Specifically, our recent review noted variability in study protocols and reported outcomes for physical functioning, inconsistencies in the magnitude of exercise-induced muscle damage and time to recovery, and a paucity of intervention studies.”] to [“Specifically, our recent review noted variability in study protocols, inconsistency of reported outcomes for physical functioning, inconsistencies in the magnitude of exercise-induced muscle damage and time to recovery, and a paucity of intervention studies.”]
• L48 we have added further context to the start of the paragraph [“Optimising recovery is important for limiting muscle soreness and restoring muscle strength following resistance exercise”]
• L240, ‘expediting’ changed to ‘improving’

 

 

Comments on the Quality of English Language

- Improve the manuscript's readability by simplifying complex sentences and avoiding jargon where possible.

• See above

Reviewer 3 Report

Comments and Suggestions for Authors

This is an interesting paper that presents new information about strategies for enhancing recovery from resistance exercise in adult humans over 70 years of age.  I have just a few comments.

Introduction:

There is no hypothesis stated.  The authors need to state their statistically testable hypothesis.  Research should be hypothesis driven with that hypothesis driving the study design, the choice of statistics, the parameters to be measured, and the interpretation of the results. 

Methods:

Why recruit individuals who had not been doing resistance exercise?  This is a rhetorical question, and the authors need to make it clear why they did not recruit individuals who were actively doing resistance exercise.

To that end, the study appears to have been done near a university.  Perhaps it is different in the UK but it seems like there are many individuals here at my university who use the gym who are over 70.  

What about lifelong exercise?  Was there an assessment of that in the initial survey? This could be important.  We do research with geriatric horses (20+ yrs of age). Most had racing careers and many who then had a second career as broodmares.  Still the question of lifelong exercise is one to ask.  I play Masters water polo at the national and international level on a team that has men in 5 yr. age brackets from 45 to 75+ years of age.  Some have come back to the sport after years.  One thing I can say personally, delayed onset muscle soreness is not delayed, but then I am just a 68-year-old youngster. 

Discussion:

The lack of a decrease in function i

Did the authors establish the repeatability of the tests and measures that they used in the study?  If so, please add that information.

Why not measure markers of inflammation?  

Author Response

We thank you very much for taking the time to review our manuscript. Please find our responses to your comments below alongside a tracked changes document with the updated manuscript.

Introduction:

There is no hypothesis stated.  The authors need to state their statistically testable hypothesis.  Research should be hypothesis driven with that hypothesis driving the study design, the choice of statistics, the parameters to be measured, and the interpretation of the results. 

• Thank you for your comment, we have now stated the hypothesis on line 58 [“It was hypothesized that consuming two servings of 500 mL of whole milk would decrease the magnitude of exercise-induced muscle damage and improve recovery time compared to the same volume of skimmed milk and a control drink”]

 

Methods:

Why recruit individuals who had not been doing resistance exercise?  This is a rhetorical question, and the authors need to make it clear why they did not recruit individuals who were actively doing resistance exercise.

• Thank you for your comment. RE has been performed a repeated bout effect is present, this is a phenomenon whereby previous performance of RE limits EIMD. This is important for two reasons; i) it allows us to establish that repeated bout effect is not present in individuals and therefore allow us to control this as a variable ii) older adults most likely to benefit from limiting EIMD are those starting RE for the first time (i.e., those who have no protection afforded by the repeated bout effect). In addition, we felt that either all participants should be regularly trained, or all untrained. A mix of training status would increase variation in response to RE. For clarification, we have included the following text [“The latter requirement was included to minimize the repeated bout effect, defined as ‘the adaptation whereby a single bout of eccentric exercise protects against muscle damage from subsequent eccentric bouts’[15]”](L84-87)

To that end, the study appears to have been done near a university.  Perhaps it is different in the UK but it seems like there are many individuals here at my university who use the gym who are over 70.  

• We agree wholeheartedly that it would have been easier to recruit older adults who already go to the gym. Indeed, it is already discussed in Table 4 (L389) that recruitment may be better in those who already participate in RE. However, as discussed previously, as a study team we chose to recruit untrained individuals to minimise the possibility of the repeated bout effect affecting EIMD measures. Also due to the repeated bout effect, untrained older adults are also likely the population with the most to gain from recovery interventions.

 

What about lifelong exercise?  Was there an assessment of that in the initial survey? This could be important.  We do research with geriatric horses (20+ yrs of age). Most had racing careers and many who then had a second career as broodmares.  Still the question of lifelong exercise is one to ask.  I play Masters water polo at the national and international level on a team that has men in 5 yr. age brackets from 45 to 75+ years of age.  Some have come back to the sport after years.  One thing I can say personally, delayed onset muscle soreness is not delayed, but then I am just a 68-year-old youngster. 

• Thank you for your comment. There was no assessment of lifelong exercise, only a RAPA (current physical activity level) as we believe the current performance of exercise, specifically RE, to be of great importance to outcomes of EIMD. With that being said, lifelong exercisers generally preserve their muscle function better than those who are sedentary (as you will have observed with your horses, and of course your teammates!). Our groups were matched on MIVC as blocking factor as a means of ensuring similar strength across groups.
• Regarding your comment about delayed onset muscle soreness; delayed onset muscle soreness is slightly different to fatigue (which can be experienced immediately after exercise). It is well-established to peak 24-48h after exercise as a result of the EIMD process (PMID 30110239)

 

Discussion:

The lack of a decrease in function i

• My apologies, I’m not sure what the reviewer intended to comment here

 

Did the authors establish the repeatability of the tests and measures that they used in the study?  If so, please add that information.

• Thank you for your comment. As discussed in manuscript, MIVC has had repeatability measures published but other secondary markers do not. [“Previously, a high short-term reliability across repeated trials has been demonstrated in leg extensor power of older adults (mean change 1.2-4.8 % from trial 1 to trial 2) [44]. Likewise, when assessing bilateral concentric knee extensor 1-RM strength, untrained older adults may need up to nine testing sessions to achieve absolute consistency of this measure [45].”](L310-314). Secondary markers have been shown to have good repeatability (again as discussed in manuscript) but they are not traditionally used for EIMD studies.

Why not measure markers of inflammation?  

• Markers of inflammation are highly variable between individuals and in the individual response to exercise. We felt with a relatively small sample (even if 36 was reached) it was very unlikely that differences would be found and hence, this was not an ethical use of research funds in addition to extra participant burden due to blood samples. For further discussion on inflammatory markers in older adults see Hayes et al (2023) (10.1186/s40798-023-00597-1)

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors adequately addressed the reviewers' recommendations. I have no further comments.