Huang et al 2015 - Doseresponse relationship of cardiorespiratory fitness adaptation to controlled endurance training in sedentary older adults

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EU RO PEAN
SOCIETY O F
CARDIOLOGY ®Original scientific paper
Dose–response relationship of
cardiorespiratory fitness adaptation to
controlled endurance training in
sedentary older adults
Guoyuan Huang1,2, Ru Wang2, Peijie Chen2, Sunny C Huang1,3,
Joseph E Donnelly4 and Jon P Mehlferber5
Abstract
Background: The purpose of this investigation was to identify a quantitative dose–response relationship for enhancing
maximal oxygen consumption (VO2max) in healthy sedentary older adults after controlled endurance training.
Methods and results: This meta-analysis of controlled clinical trials included 1257 exercisers and 845 controls with a
mean age of 67.45� 5.25 years. Effect sizes were calculated for training-induced VO2max changes. Different training
regimens were analyzed and compared. The weighted net change of the mean VO2max values showed a significant
increase of 3.78 ml/kg per min (95% confidence interval¼ 3.29 to 4.27; p< 0.0001) in response to aerobic training.
Interstudy differences in VO2max changes were significantly related to exercise intensity, and explained approximately
11% of the variance of the VO2max responses. VO2max improved significantly at 35%–50% heart rate reserve (HRR) and
continued improving at a greater rate with increasing ‘‘dose’’. The largest VO2max-improvement adaptation was achieved
with a mean intensity of 66%–73% HRR. The magnitudes of the VO2max adaptation are identical to exercise at 57%–65%
HRR and at 75%–80% HRR. Higher intensity doses more than 75–80% HRR did not lead to greater enhancement of
VO2max improvements but, conversely, resulted in large declines.
Conclusions: Our data provide quantitative insight into the magnitude of VO2max alterations as affected by exercise
intensity, duration, frequency, and program length. The shapes of the dose–response curves are not simply linear, but
with many similar trends and noteworthy characteristics. Aerobic training at a mean intensity of 66%–73% HRR with
40–50 min per session for 3–4 day/week for 30–40 weeks appears to be effective and optimal for maximum cardio-
respiratory benefits in healthy sedentary older adults.
Keywords
Controlled clinical trials, meta-analysis, VO2max, aerobic fitness, elderly, aging, sedentary, aerobic exercise, intensity,
optimal prescription
Received 18 December 2014; accepted 27 March 2015
Introduction
Aging is associated with a progressive decline in cardio-
respiratory fitness (CRF) or maximal oxygen consump-
tion (VO2max). Advanced aging accelerates the declines
in peak VO2 by 20%–25% per decade in healthy adults
over the age of 70 years1,2 and is accentuated by super-
imposed comorbidities common to the elderly such as
cardiac, pulmonary, and peripheral artery disease.3,4
Thereby, low CRF increases risks for adverse health
outcomes and diseases and will very likely affect healthy
aging and the quality of later life. Conversely, greater
1Pott College of Science, Engineering & Education, University of Southern
Indiana, Evansville, USA
2College of Exercise Science, Shanghai University of Sport, China
3Carver College of Medicine, University of Iowa, Iowa City, USA
4Department of Internal Medicine, University of Kansas Medical Center,
Kansas City, USA
5College of Arts & Letters, University of North Georgia, Dahlonega, USA
Corresponding author:
Guoyuan Huang, University of Southern Indiana, 8600 University
Boulevard, Evansville, IN 47712, USA.
Email: ghuang@usi.edu
European Journal of Preventive
Cardiology
0(00) 1–12
! The European Society of
Cardiology 2015
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DOI: 10.1177/2047487315582322
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CRF is associated with significant decreases in risks of
cardiovascular and all-cause mortality and clinical
events in individuals with preexisting diseases.4–7
Numerous studies provide evidence that one of the hall-
marks of aerobic training is to elicit CRF improve-
ments. Older adults can increase VO2max after aerobic
exercise by approximately 15%–20% or more, which is
vastly different from their healthy sedentary counter-
parts who experience an average decrease of approxi-
mately 23%.1,3
Unfortunately, older people are the least physically
active of any age group. As such, when previously sed-
entary older individuals participate in aerobic exercise,
questions about the specific amount, intensity, and
types of exercise are naturally raised. Older adults
may have exercise trainability similar to younger
adults. However, the minimum level of CRF required
for health benefits and optimal exercise program may
differ greatly for sedentary older adults,5 who com-
monly have chronic medical conditions, low fitness
levels, and/or functional limitations.4 Importantly, the
precision of the dose-relationship for VO2max improve-
ment response to aerobic training can vary from subject
to subject as a function of genetic-, age- and/or health-
related factors, metabolic stress, and/or physical train-
ing level.6–9
Professional organizations make recommendations
for the general population including older adults.6,7,10
But the ‘‘dose’’ or characteristics of aerobic exercise,
that is, the intensity, duration, frequency, and length
of training required to achieve and optimize the
response of specific health outcomes, remains uncer-
tain.6 The quantitative dose–response relationship
regarding the VO2max adaptation to endurance training
in healthy sedentary older adults is also less clear.5 For
example, the ceiling of VO2max response for training
intensity and the optimal intensity to yield more bene-
fits for CRF remains unknown.11 Moreover, potential
adverse cardiovascular effects from excessive endurance
exercise have been reported.12 Whether vigorous exer-
cises are more cardioprotective than are moderate exer-
cises is not highly persuasive,13 and vigorous physical
exertion is associated with an increased risk for cardiac
events, especially in sedentary and risk individuals.6,7
Furthermore, it is still less possible to describe in
detail exercise programs that will optimize physical
functioning and general health in all groups of adults;
and the individualized exercise prescription for specific
health benefit needs further development and
evaluation.3,7
Therefore, this meta-analytic study, which synthe-
sized the results of clinical trials that assessed the
VO2max adaptation to controlled endurance training
in apparently healthy, but previously sedentary, older
adults was conducted to qualify the dose–response
relationship between different training regimens and
the induced VO2max improvements.
Methods
Data search and selection
A meta-analysis approach was used according to stand-
ard procedures and PRISMA guidelines.14 Pertinent
articles were identified by a systematic computer data-
base search, hand searching relevant journals and ref-
erence lists, and cross-referencing previously located
studies. A broad rather than a specific search was uti-
lized to locate relevant articles. The initial search strat-
egy used keywords either alone or in various
combinations. A reference librarian was consulted
throughout the search process. The inclusion criteria
were: controlled clinical trials; mean ages of subjects
�60 years; with aerobic exercise training as the only
intervention; presence of a non-exercise control
group; a measure of changes in VO2max; studies fully
published in English-language peer-reviewed journals
after 1980; training program lasting a minimum of
two weeks; and components of the training regimen
reported inquantifiable terms. Excluded were studies
with confounding factors introduced by some other
interventions, such as combination of endurance train-
ing and diet or weight loss programs. Relevant
abstracts from publications, conference proceedings,
or dissertations were checked, but excluded.
Study extraction and quality assessment
A standardized coding sheet was used to extract data.
Inter- and intra-rater reliability checks were performed
for 12 studies (23.5%) to control for drift. Based on the
results of reliability checks, necessary alterations were
made with regard to the operational definitions and
data inclusion criteria. Some investigations enabled
the calculation of multiple study treatment effects. If
a study contained more than one experimental group,
then each group mean was treated as a single data
point.
Data synthesis and analysis
The standardized effect size for an individual study was
calculated. This standardized effect size for each meas-
ure was estimated from reported means and standard
deviations in the included studies. Overall net changes
in VO2max outcomes were calculated as the difference
(exercise minus control) of the changes (pre-interven-
tion minus post-intervention) in those mean values.
Publication bias was examined using a funnel plot
and study quality was assessed applying a validated
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and reliable questionnaire.15 The Q-statistic was used to
assess homogeneity of results for the standardized effect
sizes. The I2 test was incorporated to assess inconsist-
ency across the trial results. Statistical analysis was con-
ducted with Comprehensive Meta-Analysis (Biostat)
and SPSS. Descriptive statistics were calculated.
Subgroup analyses were performed on categorical vari-
ables. Relationships of effect size changes in response to
aerobic exercise were analyzed when data were parti-
tioned according to levels of training regimens.
Weighted meta-regression analysis was applied to
assess whether variations in the results were related to
variations in training characteristics and the interested
variables. Whenever appropriate, t-test or ANOVA
with post hoc tests was performed to identify mean
differences. Results were reported as weighted means,
standard deviation unless otherwise noted, and with a
95% confidence interval (95% CI). Level of significance
was set at p�0.05.
Results
Fifty effect sizes were calculated from 41 controlled
clinical trials.16–56 VO2max outcomes were derived
from a total of 2102 apparently healthy but sedentary
older subjects. The initial physical characteristics of the
exercise and control groups were: age (years), 67.1� 4.7
vs. 67.7� 5.4; height (cm), 164.8� 6.4 vs. 164.8� 7.0;
weight (kg), 70.1� 7.2 vs. 70.0� 8.2; body mass index
(BMI) (kg/m2), 25.7� 1.5 vs. 25.5� 1.9; body fat (%),
30.6� 6.1 vs. 30.3� 6.5; heart rate at rest (beats/min),
72.7� 6.8 vs. 69.8� 6.4; systolic blood pressure
(mmHg), 136.4� 11.8 vs. 134.1� 10.9; and diastolic
blood pressure (mmHg), 81.6� 6.6 vs. 81.0� 6.6,
respectively. Initial VO2max values ranged from 14.7
to 30.8ml/kg per min for exercisers and 15.8 to
31.5ml/kg per min for controls. No statistically signifi-
cant mean differences were found between the two
groups.
Table 1 presents baseline data and net changes for
VO2max in adaptation to aerobic training. After
intervention, controls had no changes in VO2max with
a slight non-significant mean reduction of 0.27ml/kg
per min (95% CI¼�2.08 to 1.54; p¼ 0.769). In con-
trast, exercisers showed statistically significant increases
in VO2max net changes, with an overall weighted mean
value of 3.78ml/kg per min or a 16.3% improvement
(95% CI¼ 3.29 to 4.27; p< 0.0001). The pooled stan-
dardized effect size by a fixed-effect model showed a
moderately higher effect of 0.64� 0.05 (mean�SEM,
95% CI¼ 0.56 to 0.73; p< 0.0001). No statistically sig-
nificant heterogeneity was observed for the effect sizes
(Q¼ 66.03, p> 0.05). The value of I2 test was 25%,
indicating no significant variability between studies.
Visual inspection of the funnel plots showed absence
of publication bias. Study quality analysis ranged
from 0 to 4 (2� 1). Coder drift (the percent agreement
for each study) was 96% or greater, demonstrating that
the coding-process was reliable.
Table 2 provides a description of each included inter-
vention in terms of major characteristics of the study,
subjects, and exercise training. Characteristics of exer-
cise dose parameters are presented in Table 3. Program
length: length of exercise intervention varied from eight
to 52 weeks. Twenty-three groups (46%) had training
intervention lasting 8–20 weeks; 22 groups (44%) lasting
20–40 weeks; five groups (10%) lasting 40–52 weeks.
Frequency: most programs (38 groups, 76%) trained
subjects approximately 2.9–3.9 days/week. Nine
groups (18%) trained more than 4–4.9 days/week, and
three groups (6%) trained 1–2.5 days/week. Duration:
time of each training session ranged from 20 to 60min.
The mean duration for most groups (34 groups, 68%)
lasted 35–50min. Intensity: the exercise intensity varied
and was expressed as percent maximum heart rate
(% HRmax), percent VO2max reserve (%VO2R) %
VO2max, % VO2R, % HRR, or HRmax. The most com-
monly used intensity measurements were % HRR (56%
of the groups) and % HRmax (38% of the groups).
Mode: exercise programs used one or more of the fol-
lowing aerobic modalities: walking, jogging, running,
cycling, stair-climbing, aerobic dancing, outdoor
Table 1. Baseline data and net changes for VO2max in adaptation to endurance training.
Variable
Baseline Net change
N Mean� SD Mean� SEM (95% CI) p value
VO2max (ml/kg per min)
Control 845 23.47� 3.96 �0.27� 0.91 (�2.08, 1.54) ¼ 0.769
Exercise 1257 23.03� 3.84 3.50� 0.84 (1.83, 5.17) ¼ 0.000
Weighted overall 2102 – 3.78� 0.28 (3.24, 4.33) ¼ 0.000
VO2max: maximum oxygen consumption; N: number of subjects in reporting data; SD: standard deviation; SEM: standard error of mean; CI: confidence
interval
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Table 2. Characteristics of the included exercise interventions.
Citation Na
Ageb
(years) Gender RCT
Length
(weeks) Description of exercise programc
Ahmaidi et al.16 8 62.9 Mixed No 12 Walking, jogging/running track; 60%
HRR/HR at 129 beats/min; 40 min;
2/week
Babcock et al.17 8 72.0 Male No 24 Monark cycle ergometer; 80% VO2max;
30 min; 3/week
Badenhop et al.18 (1) 11 70.0 Mixed Yes 9 Cycle ergometer; 57% VO2max/38.4%
HRR/HR at 112 beats/min; 25 min;
3.1/week
(2) 10 67.1 Mixed Yes 9 Cycle ergometer; 70% VO2max/59.6%
HRR/HR at 125 beats/min; 25 min;
3.1/week
Belman and Gaesser19 (1) 8 68.8 Mixed Yes 8 Walking/outdoor; 53% VO2max/35%
HRR/LT at 72%; 30 min; 4/week
(2) 8 69.4 Mixed Yes 8 Walking/outdoor; 82% VO2max/75%
HRR/LT at 121%; 30 min; 4/week
Binder et al.20 23 65.0 Female No 36 Walking, jogging, stair-climbing;
73%–82% HRmax; 41 min; 3.5/week
Blumenthal et al.21 31 67.7 Mixed Yes 16 Cycle ergometer, brisk walking, jogging;
60% HRR; 45 min; 3/week
Braith et al.22 (1) 19 66.0 Mixed Yes 26 Walking, jogging/uphill, treadmill; 70%
HRR; 40–45 min; 3/week
(2) 14 65.0 Mixed Yes 26 Walking, jogging/uphill, treadmill; 70%–
85% HRR; 35–40 min; 3/week
Buchner et al.23 (1) 21 75.0 Mixed Yes 12 Walking/outdoor, stationary cycle, aer-
obic lower body movements; 77%
HRR; 35–40 min; 3/week
(2) 22 74.0 Mixed Yes 12 Walking/outdoor, stationary cycle, aer-
obic lower body movements; 69%HRR; 35–40 min; 3/week
(3) 22 75.0 Mixed Yes 12 Walking/outdoor, stationary cycle, aer-
obic lower body movements; 80%
HRR; 35–40 min; 3/week
Carroll et al.24 18 72.1 Mixed No 26 walking/treadmill, stair-climbing; 63.9%–
77.9% HRR; 30–45 min; 3/week
Carroll et al.25 (1) 28 66.9 Mixed No 26 Walking/treadmill, gym floor; 60–70%
HRR; 40–45 min; 3/week
(2) 17 65.0 Mixed No 26 Walking/treadmill, gym floor; 65%–85%
HRR; 35–40 min; 3/week
Cunningham and Rechnitzer26 100 62.9 Male Yes 52 Walking, jogging; 66%–71% HRR/HR at
126–132 beats/min; 31.6 min; 3/week
DeVito et al.27 11 63.1 Female Yes 12 Walking; 77%HRmax/58% HRR/HR at
118 beats/min; 20–25 min; 3/week
Engels et al.28 10 68.6 Mixed Yes 10 Aerobic dance; 50%–70% HRmax;
30 min; 3/week
Fahlman et al.29 15 76.0 Female Yes 10 Walking; 70% HRR; 50 min; 3/week
Gillett et al. 30 69 64.4 Female Yes 16 Lower-impact aerobic dance; 60%–80%
HRR; 25.3 min; 3.8/week
Hagberg et al.31 16 71.8 Mixed Yes 13 Walking, jogging; 50%–70% VO2max;
35–40 min; 3/week
(continued)
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Table 2. Continued
Citation Na
Ageb
(years) Gender RCT
Length
(weeks) Description of exercise programc
Hill et al.32 87 64.0 Mixed No 42 Walking/uphill treadmill, indoor track
running; 60%–80% HRmax; 30–
50 min; 3–4/week
Jessup et al.33 11 67.8 Mixed Yes 16 Walking, stair-climbing, treadmill; 50%–
85% HRmax; 35 min; 3/week
King and Brassington34 11 60.2 Mixed No 16 Brisk walking; 60%–75% HRR; 30–
40 min; 4/week
Kohrt et al.35 18 66.0 Female No 36 Walking, jogging, stair-climbing; 79%
HRmax/HR at 126 beats/min; 45 min;
3.3/week
Kohrt et al.36 (1) 53 63.7 Male No 36 Walking/treadmill, indoor track run-
ning, cycle/rowing ergometers; 80%
HRmax; 46 min; 4/week
(2) 57 64.0 Female No 36 Walking/treadmill, indoor track run-
ning, cycle/rowing ergometers; 79%
HRmax; 45 min; 3.9/week
Kohrt et al.37 5 65.0 Female No 36 Walking, jogging/treadmill; stair-climb-
ing; 73%–82% HRmax; 42.5 min; 3.45/
week
Lan et al.38 (1) 9 65.2 Male No 48 Tai Chi in park; 78.2% HRmax/52%–63%
HRR/HR at 121 beats/min; 24 min;
4.6/week
(2) 11 64.9 Female No 48 Tai Chi/in park; 74.8% HRmax/52%–63%
HRR/HR at 116 beats/min; 24 min;
4.6/week
Madden et al.39 25 66.5 Mixed Yes 16 Walking, jogging, cycle/arm ergometer;
70% HRR; 45 min; 3/week
Panton et al.40 17 71.8 Mixed Yes 26 Walking, jogging; 60%–85% HRR;
40 min; 3/week
Panton et al.41 10 66.0 NA Yes 16 Walking, stair-climbing, treadmill; 70%–
85% HRR; 40 min; 3/week
Posner et al.42 166 68.6 Mixed Yes 16 Monarch cycle ergometer; 76% HRmax/
70% VO2max/45% HRR/HR at 115
beats/min; 30 min; 3/week
Probart et al.43 10 72.0 Female Yes 26 Walking/treadmill; 70%HRmax; 20 min;
3/week
Puggaard et al.44 19 85.0 Female Yes 32 Walking, aerobic performance;
69%HRmax; 60 min; 1/week
Ready et al.45 (1) 18 61.3 Female Yes 24 Walking/track; 60% VO2max; 59 min;
2.9/week
(2) 17 61.3 Female Yes 24 Walking/track; 60% VO2max; 57 min;
4.9/week
Schuit et al.46 27 65.1 Mixed Yes 24 Jogging outdoor, aerobic exercise to
music, running ball game; 70%–80%
VO2max; 30 min; 3/week
Seals et al.47 11 63.0 Mixed No 24 Walking; 60% HRmax/40% HRR/HR at
107 beats/min; 27 min; 4.6/week
Seals et al.48 10 62.0 Mixed No 24 Cycling, graded treadmill walking/jog-
ging; 80%–90% HRmax; 30–45 min; 3/
week
(continued)
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aerobic performance, and aerobic games.
Approximately 41 groups (82%) used walking and/or
jogging as the primary training modality; 13 groups
(26%) applied cycle ergometer; seven groups (14%)
used stair-climbing; 12 groups (24%) applied other mod-
alities such as aerobic dancing, Tai Chi, aerobic lower
body movements, mini-tennis, and running ball games.
The weight mean effect sizes, representing exercise-
induced VO2max net changes, were grouped by mean
training intensity: 35%–50%, 57%–65%, 66%–73%,
and 75%–80% of HRR. For analysis purpose, all
other intensity measurements were converted into %
HRR by referring to the recognized guidelines.10 The
results revealed that training at 66%–73% HRR elicited
the largest mean effect size over all the other three
groups. The 35%–50% HRR group had the smallest
effect size, which was significantly lower than the
66%–73% HRR (0.51� 0.26 vs. 0.99� 0.50;
p¼ 0.026), but not significantly lower than the 57%–
65% HRR (0.69� 0.33; p¼ 0.703) and the 75%–80%
HRR (0.66� 0.42; p¼ 0.851) groups. Although there
were noteworthy mean differences in effect sizes of
VO2max net changes between 66%–73% HRR and
57%–65% HRR (mean� SEM, 0.31� 0.14; 95%
CI¼�0.07 to 0.69; p¼ 0.145) and 75%–80% HRR
(mean� SEM, 0.34� 0.17; 95% CI¼�0.11 to 0.78;
p¼ 0.198), they were not statistically significant.
The analysis was performed for the weighted mean
effect size of VO2max net changes grouped by mean pro-
gram length: 8–12 weeks (0.69� 0.54), 13–20 weeks
(0.65� 0.28), 24–28 weeks (0.68� 0.34), 32–36 weeks
(1.30� 0.19), and 42–52 weeks (0.67� 0.38). The results
showed that 32–36 weeks had the largest mean effect
size value among all groups. The mean differences of
Table 2. Continued
Citation Na
Ageb
(years) Gender RCT
Length
(weeks) Description of exercise programc
Seals and Reiling49 14 61.0 Mixed No 28 Walking; 47% HRR; 41 min; 3.5/week
Shin50 14 67.5 Female No 8 Walking/outdoor track; 40%–60% HRR;
30–40 min; 3/week
Sunami et al.51 20 67.0 Mixed Yes 20 Walking, cycle ergometer, dancing; 50%
VO2max; 218 min/week, 60 min; 3/
week
Takeshima et al.52 11 68.9 Mixed No 12 Walking, stationary ergometer, aerobic
dancing, mini-tennis; 70% HRmax/
50%–67% VO2max; 60 min; 3/week
Tanaka et al.53 11 62.0 Mixed No 26 Walking; 45% HRR; 42 min; 3.4/week
Thomas et al.54 11 68.0 Male No 16 Walking/treadmill, cycle ergometer,
stair-climbing, rowers; 60%–80%
HRmax; 45 min; 4/week
Thomas et al.55 88 62.9 Male Yes 52 Walking/jogging/outdoor-indoor track;
69.57% HRR; 30 min; 2.5/week
Whitehurst56 7 65.8 Female Yes 8 Cycling/ergometer; 70%–80% HRmax;
35–40 min; 3/week
aNumber of exercise subjects. bMean values presented. cMode, intensity, duration, and frequency. RCT: randomized controlled trial; HRR: heart rate
reserve; HRmax: maximum heart rate; VO2max: maximum oxygen consumption; LT: lactate threshold.
Table 3. Training program characteristics and weighted coefficients of VO2max changes to training regimens.
Variable N Mean� SD Rangea r (95% CI)b R2 p
Age (years) 50 67.10� 4.69 60.2–85.0 0.148 (�0.051, 0.160) 0.022 ¼0.306
Length (week) 50 22.72� 12.10 8–52 0.235 (�0.007, 0.074) 0.055 ¼0.100
Frequency (days/week) 50 3.25� 0.66 1–4.9 �0.156 (�1.166, 0.342) 0.024 ¼0.278
Duration (min) 50 38.12� 10.01 20–60 �0.187 (�0.017, 0.081) 0.035 ¼0.194
Intensity (% HRR) 50 63.24� 11.36 35–80 0.328 (0.008, 0.091) 0.108 ¼0.020*
aRange¼ between-study range. br¼ the weighted metaregression coefficient representing dose response between the weighted net changes in
VO2max and the aerobic training program, and 95% CI. *p< 0.05. VO2max: maximum oxygen consumption; N: number of groups reporting data;
SD: standard deviation; CI: confidence interval; HRR: heart rate reserve
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//blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/CPRJ/Vol00000/150023/APPFile/SG-CPRJ150023.3d (CPR) [PREPRINTER stage]effect sizes were higher and statistically significant for
32–36 weeks compared with 8–12 weeks of�0.61� 0.32
(mean� SEM; 95% CI¼�1.16 to �0.69; p¼ 0.020),
with 13–20 weeks of �0.65� 0.20 (mean� SEM; 95%
CI¼�1.23 to �0.07; p¼ 0.020), and with 24–28 weeks
of �0.62� 0.19 (mean� SEM; 95% CI¼�1.16 to
�0.08; p¼ 0.016). The effect size of VO2max net
change in 24–28 weeks was also significantly larger
than that of 8–12 weeks (mean� SEM, 0.61� 0.19;
95% CI¼ 0.07 to 1.16; p¼ 0.020). There was a note-
worthy mean difference (mean� SEM, 0.63� 0.24;
95% CI¼�0.05 to 1.30; p¼ 0.080) between 32–36
weeks (1.30� 0.19) and 42–52 weeks (0.67� 0.38),
though it was not statistically significant.
Trends of the greatest effect size in VO2max net
changes were observed when the mean duration of
training session was approximately 45min and the
training frequency averaged about 3.5 days/week.
There was also a trend that older individuals with
mean age of 70–85 years had a larger effect size than
those with mean age of less than 65 years. However,
these mean differences were not statistically significant.
Table 3 shows the results of weighted single metare-
gression analysis. Results revealed a statistically signifi-
cant association and a medium coefficient between the
weighted net changes in VO2max and the mean intensity
of the training program, which explained approxi-
mately 11% of the variance of the VO2max responses.
The association and coefficients of the VO2max
responses to other exercise regimens were noticeable
but not statistically significant. Figure 1 illustrates the
overall net changes of VO2max gains expressed as the
calculated effect sizes response in the aerobic exercise
regimen. The graphs depict the trend, shape, and size of
curves. They present evidence-based information that
reflects a composite of the dose–response relationship
in these 50 exercise interventions of aerobic exercise
training dose and VO2max responses or adaptive
changes.
Discussion
Key findings
The primary findings are: 1) relationships of the
VO2max adaptation to aerobic training stimulus do
not follow a simple linear, same-shape dose–response,
but have many similar trends and noteworthy charac-
teristics (Figure 1); in general, a maximal VO2max would
be induced by aerobic training approximately at 70%
HRR intensity, 45min duration, and 3.5 days/week for
36 weeks; 2) healthy sedentary older adults begin
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
1.1
1.2
1.3
E
ff
e
ct
 s
iz
e
Mean intensity (%HRR)
0.4
0.5
0.6
0.7
0.8
0.9
1
1.1
1.2
1.3
E
ff
e
ct
 s
iz
e
Mean duration (min)
0.6
0.65
0.7
0.75
0.8
0.85
0.9
0.95
1
E
ff
e
ct
 s
iz
e
Mean frequency (days/week)
0.4
0.5
0.6
0.7
0.8
0.9
1
1.1
1.2
1.3
1.4
35 40 45 50 55 60 65 70 75 80
15 20 25 30 35 40 45 50 55 60 65
1.5 2.52 3.5 4.5 543
8 12 16 20 24 28 32 36 40 44 48 52
E
ff
e
ct
 s
iz
e
Mean length (weeks)
(a)
(b)
(c)
(d)
Figure 1. (a) Overall net changes of VO2max gains expressed as the calculated effect size response to aerobic training intensity;
(b) overall net changes of VO2max gains expressed as the calculated effect size response to aerobic training duration; (c) overall net
changes of VO2max gains expressed as the calculated effect size response to aerobic training frequency; (d) overall net changes of
VO2max gains expressed as the calculated effect size response to aerobic training length.
VO2max: maximum oxygen consumption; HRR: heart rate reserve
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attaining VO2max improvements at training intensity of
35%–50% HRR; VO2max reaches a peak adaptation
after intensity progresses to 70%–73% HRR; training
at 57%–65% HRR is just as effective as higher inten-
sities of 75%–80% HRR in VO2max-gain; however,
intense training at more than approximately 73%
HRR does not necessarily lead to further enhancement,
but, inversely, to a VO2max-gain decline; 3) a longer
training length of approximately 20–24 weeks is
needed for older individuals to begin eliciting greater
VO2max; training for 32–36 weeks is optimal to achieve
a peak VO2max adaptation, while the magnitude of
VO2max gains declines progressively after more than
36–40 weeks of training; 4) VO2max gains show a peak
adaptation to training for 40–50min per session, with
approximately 45min eliciting the maximum; however,
a longer duration over 50min provides no more bene-
fits, but declines in VO2max-gain; 5) training for 6–7
days biweekly is optimal to elicit the peak VO2max adap-
tation, while training more than 4–5 days/week adds no
greater CRF benefits but leads to a VO2max-gain
decrease.
Intensity and VO2max change
Our data reveal strong evidence for a dose–response
relationship between exercise intensity and VO2max
adaptation (Figure 1(a)). The VO2max-gain is directly
dependent on training intensity, but within a proper
range for maximum benefits. This dose–response
curve depicts the mean intensity, ranging from 35%
HRR to 80% HRR, inducing VO2max improvements.
But it appears somewhat negatively skewed, implying
slow but steady VO2max-gain increases with training
intensities from light to moderate. It should be indi-
cated that, while VO2max responses vary to different
intensities, the overall net changes of VO2max gains
are statistically significant. Thus, trained within this
intensity range, or at an average intensity of approxi-
mately 63% HRR, healthy sedentary older individuals
could elicit a moderately higher effect of 0.64, repre-
senting approximately a weighted mean value of
3.78ml/kg per min, or a 16.3% improvement in
VO2max when compared with non-exercisers.
Our data analysis qualifies the possible ‘‘trigger-
point’’ of effective VO2max increases response to inten-
sity around 35%–50% HRR. While the amount of
VO2max gains appears small, this statistically significant
change supports the assertion that light-to-moderate
aerobic exercise improves health-related CRF. This
35%–50% HRR range may suggest the proper begin-
ning dose of intensity for VO2max enhancement.
There is possibly an intensity ‘‘drifting-point’’ for
VO2max increases. When training intensities go above
50% HRR, VO2max gains drift steadily upward until
the intensity dose reaches about 65%–67% HRR.
The VO2max-gain response to 50%–65% HRR
increases approximately 35% compared with that of
response to 35%–50% HRR, supporting that ‘‘some
is good’’, but ‘‘more is better’’.5,6 However, more com-
prehensive inquiries need to determine whether these
data suggest a training intensity or a threshold of
greater VO2max gains for healthy sedentary elderly.
Our results demonstrated that training at the 66%–
73% HRR intensities elicited the largest mean effect
size over all the other three groups, which probably
represents a training-adaptation-sensitive zone for max-
imal cardiorespiratory benefits in healthy sedentary
older people. This zone begins at a ‘‘turning-point’’
with intensities around 65%–67% HRR. With the
intensity exceeding this point, VO2max-gain responses
show a sudden and rapid rise until reaching the greatest
level. As such, the ‘‘turning-point’’ possibly indicates the
trigger intensity threshold of the maximal adaptive cap-
acity. As such, this ‘‘turning-point’’ triggering the
VO2max acceleration may mirror the improved
Table 4. Recommendation of prescribing aerobic exercise program for VO2max improvement in healthy older adults.
Variable Small VO2max gain Moderate VO2max gain Large VO2max gain
Intensity
% HRR 35–50 50–65 65–75
% HRmax 60–70 70–79 79–86
METs 2.8–4 4–5.1 5.1–5.8
Perceived Exertion Light to fairly light Fairly light to somewhat hard Somewhat hard to hard
RPE 10–12.5 12.5–14.5 14.5–15.5
Duration (min/day) 20–30 30–40 40–50
Frequency (days/biweekly) 4–5 5–7 7–8
Length (week) 8–20 20–30 30–40VO2max: maximum oxygen consumption; HRR: heart rate reserve; HRmax: maximum heart rate; MET: metabolic equivalent (1 MET¼ individual
metabolic resting demand when sitting quietly, about 3.5 ml oxygen/kg per min); RPE: Borg rate of perceived exertion on the 6–20 scale
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adaptation of aging physiological systems that are
beneficial or accumulated from prior training with
lower intensities.
This training-adaptation-sensitive zone includes a very
narrow range of intensities. By just adding 5–6 units, the
VO2max-gain reaches a ‘‘ceiling’’ level, representing an
approximately 45% increase from 65%–67% HRR to
70%–73% HRR. Given that excessive prolonged high
intensity exercise may increase the risk of developing
maladaptations, or even negative events,6,7 especially in
aging people,12 caution should be used for progression
rate of intensity within or above this zone.
The ceiling of VO2max-gain response for training
intensity remains unknown.11 In our study, it appears
at intensity around 70%–73% HRR, corresponding to
a Borg rate of perceived exertion (RPE) of approxi-
mately 15 on a 6–20 scale, or approximately seven
metabolic equivalents (METs).6,10 This intensity ceiling
probably represents an upper limit of VO2max-gain
adaptation for healthy sedentary older individuals.
Our data provide strong evidence that with training
intensity above 70%–73% HRR, no further VO2max-
gain occurs but, inversely, declines dramatically.
Diminishing returns appear to begin immediately
after training-adaptation-sensitive zone around the ceil-
ing, indicating the VO2max-gain drop as mean training
intensity exceeds 70%–73% HRR. Sharp declines con-
tinue progressively regardless of the exertion level
before the highest mean intensity. Our analyses also
showed a significant large mean difference in effect
size between 66%–73% HRR (0.99� 0.50) and 75%–
80% HRR (0.66� 0.42), suggesting a dramatic drop
rate that corresponds to approximately 34% of
decreases by adding just 5–7 units of % HRR above
the ceiling of 70%–73% HRR. These results imply that
vigorous exercise exceeding a certain intensity range
may not always be better or necessary to produce
more VO2max-gain for older adults.
Interestingly, Figure 1(a) depicts a high–moderate
effect size for VO2max-gain in response to both mean
intensities of 57%–65% HRR (0.69� 0.33) and 75%–
80% HRR (0.66� 0.42), demonstrating that training at
both intensities elicits the identical response of VO2max
improvements. The results imply that training at inten-
sity above 75%–80% HRR adds no additional CRF
benefits. Older individuals can opt to train at moder-
ate–hard intensities instead of higher-hard intensities,
but still acquire similar health-related cardioprotective
benefits. Given that excessive training intensity and
abrupt increases in training volume increase the risk
of injuries and adverse cardiovascular effects,6,7,12 cau-
tion should be taken when prescribing aerobic exercise
with high intensity more than the 70%–73% HRR ceil-
ing for healthy sedentary older individuals until further
data are available.
Duration and VO2max change
The duration–response curve (Figure 1(b)) showed a
similar shape and trend to the intensity curve, implying
the two may be closely interrelated to each other. The
particular time range of 40–50min per session appears
to promote better aerobic fitness than both shorter
(<40min) and longer (>50min) duration of exercise.
Diminishing returns begin after 45min training, and
the VO2max-improvement drop becomes progressive
and sharp when training over 50min, suggesting that
cardiorespiratory benefit may diminish for older indi-
viduals if the training session is too long. These results
may reflect the diminished cardiovascular changes and
responsiveness with advancing age that could contrib-
ute significantly to the reduced cardiovascular perform-
ance during prolonged exercise.57 At any submaximal
exercise load, older adults are often required to exert a
higher percentage of their maximal capacity and typic-
ally present an accelerated onset of fatigue.58 These
may result in inability of response to or decreased tol-
eration of aerobic training, even adverse cardiovascular
effects,12 when high intensity and excessive duration are
more than optimal.
Frequency and VO2max change
The frequency–VO2max-response curve (Figure 1(c))
generally supports the recommendations for exercise
frequency from professional organizations,6,10 but sup-
plements it with the following information: 1) 3–4 days/
week aerobic exercise may be sufficient to induce
greater cardioprotective benefits in healthy sedentary
older individuals, with a peak VO2max adaptation
from training of 3.5 days/week; 2) 2–3 days/week train-
ing may acquire a magnitude of VO2max-improvement
similar to exercising 4–5 days/week; and 3) exercise
more than 4–5 days/week may diminish benefits of
this VO2max- gain. More independent and clinical con-
trolled studies are needed to confirm the results.
Length and VO2max change
Our comparison data showed the largest VO2max-gain
with training of around 35–36 weeks, suggesting a need
for an adequate longer exercise period for older adults
to attain greater VO2max. Decreased reductions of rest-
ing heart rate responding to longer aerobic training of
more than 30 weeks have been reported in healthy sed-
entary older subjects.59 Reductions in peak heart rate
and peripheral oxygen utilization appear to mediate the
age-associated decline in aerobic capacity with an accel-
erated rate in later life,57 which may contribute to the
longer trainability, the declined adaptation to greater
VO2max attainment, and the difficulty to maintain
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training benefits in aging people. Each person’s genetic
ceiling again limits the extent of improvement that is
possible due to exercise training. Our study found that
a ‘‘ceiling’’ exists around 36 weeks, above which
VO2max gains appear to progressively decline in magni-
tude. By approximately 50 weeks of training, VO2max
gains are almost identical to those of 8–12 weeks, pre-
senting a 48% decline compared with the peak level.
Thus, 36–40 weeks could be considered as an optimal
training length for the desired CRF level and the time
of transition to maintaining exercise on a regular, long-
term basis.
Although training of about 8–12 weeks significantly
improved VO2max, progressive rate of change was slow
and remained almost unchanged throughout the course
to about 20–24 weeks. This may imply that physio-
logical adaptations, including cardiorespiratory, mus-
cular, metabolic, neural, and endocrine, to an
augmented exercise regimen would take as long as
20–24 weeks in healthy sedentary older adults. The
comparison between mean VO2max net changes in 24–
28 weeks and in 8–12 weeks was statistically significant,
implying that 24–28 weeks may represent a training
length threshold associated with the trainability of
older adults and great VO2max-gain adaptation.
Genetic factors could produce a larger variation in
the trainability of VO2max response. Bouchard et al.
found that some subjects elicited little or no improve-
ment in VO2max response to a 20-week endurance train-
ing program.8 Considering our findings, it would be an
interesting area for further study within the biology of
fitness and its adaptation to regular aerobic exercise to
see whether training more than 20 weeks would change
the variationand adaptive capacity in these subjects.
Specific recommendations are currently not available
with regard to aerobic exercise length for older adults,
although the Position Stand of American College of
Sports Medicine provides a reference for all adults.5
Thus, our findings add useful information regarding
the optimal length prescription of aerobic training for
greater CRF development in healthy sedentary older
adults.
Limitations and implications
Older individuals exhibit a greater reduction in exercise
tolerance and an increased risk of illness/injury during
the combined demands of large muscle exercise and
heat/cold stress.3 Due to lack of information in the
included studies, the possibility is not excluded that
environmental influence on training would possibly
affect our dose–response results. Due to lack of infor-
mation we could not evaluate the validity and reliability
of the VO2max results that were analyzed for the dose–
response relationship. Because the coding was based on
the short descriptions of often-complex programs in the
published articles, the coding of exercise content may
not completely reflect the real nature of the program.
Hence, our results must be interpreted cautiously.
However, this meta-analysis provides data that were
derived from 41 controlled clinical trials with a large
sample size consisting of older individuals with a nar-
rowed mean age range from 60 to 85 years. The pooled
standardized effect size was calculated by a fixed-effect
model and showed a moderately higher effect. No sig-
nificant heterogeneity, the lack of significant variability
between studies, absence of publication bias, and high
correlation of reliability for data abstraction demon-
strated that the coding-process and outcomes were
valid and reliable. Accordingly, the overall results and
findings are robust, evident, and generalizable to a rela-
tively broad section of older people who are apparently
healthy but sedentary. As such, we propose Table 4
as a reference for professionals and older adults to
optimize aerobic exercise for maximal cardiorespiratory
health.
Conclusion
Derived from prospective, controlled clinical trials,
the current study reveals evidence of a quantitative
dose–response relationship between aerobic training
regimens and VO2max adaptations. This meta-analysis
identified some striking results and provided the
quantitative information about optimizing aerobic
training intensity, duration, frequency, and length
for maximal CRF development in healthy sedentary
older adults. There is a strong dose–response relation-
ship that VO2max improvements are directly depend-
ent on training intensity, but within a proper range.
An ‘‘intensity ceiling’’ evidently exists and appears
around 70%–73% HRR, corresponding approxi-
mately to an RPE of 15 or 7 METs.6,10 The intensity
range of 66%–73% HRR probably represents a train-
ing-adaptation-sensitive zone for maximal CRF bene-
fits. However, higher doses of training above 70%–
73% HRR do not necessarily induce further enhance-
ment of this effect but, inversely, gains dramatically
decline. Three other exercise characteristics also show
similar trends and shapes of such relationships quan-
titatively that appear to effectively influence VO2max
gains. Exercise prescription is a complex process and
requires manipulating individual training regimens.
Our findings should be consulted for different pur-
poses by researchers, healthcare providers, exercise
science professionals, and the general older popula-
tion. The findings need to be confirmed with
large, well-designed, randomized controlled trials.
Comprehensive research designs, utilizing a combin-
ation of two or more exercise regimen components
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for an exercise intervention, are recommended for
prospective future research in this area.
Funding
This work was supported in part by a grant from Science and
Technology Commission of Shanghai Municipality, China
(grant number STCSM#13490503500 to RW).
Conflict of interest
The authors declare that there is no conflict of interest.
Acknowledgements
The authors thank Dr Kenneth Powell for his comments and
suggestions.
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