Adverse metabolic response to regular exercise: is it a rare or common occurrence?

Bouchard, Claude; Blair, Steven N.; Church, Timothy S.; Earnest, Conrad P.; Hagberg, James M.; Häkkinen, Keijo; Jenkins, Nathan T.; Karavirta, Laura; Kraus, William E.; Leon, Arthur S.; Rao, D. C.; Sarzynski, Mark A.; Skinner, James S.; Slentz, Cris A.; Rankinen, Tuomo

doi:10.1371/journal.pone.0037887

Cited by 389Physical Activity and HealthCardiovascular and exercise physiologyDiabetes, Cardiovascular Risks, and Lipoproteins

Adverse metabolic response to regular exercise: is it a rare or common occurrence?

Open access

Bouchard, Claude, Blair, Steven N., Church, Timothy S., Earnest, Conrad P., Hagberg, James M., Häkkinen, Keijo, Jenkins, Nathan T., Karavirta, Laura +7 more·2012·PLoS ONE

DOI 10.1371/journal.pone.0037887PMC PMC3364277

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Abstract

BACKGROUND: Individuals differ in the response to regular exercise. Whether there are people who experience adverse changes in cardiovascular and diabetes risk factors has never been addressed. METHODOLOGY/PRINCIPAL FINDINGS: An adverse response is defined as an exercise-induced change that worsens a risk factor beyond measurement error and expected day-to-day variation. Sixty subjects were measured three times over a period of three weeks, and variation in resting systolic blood pressure (SBP) and in fasting plasma HDL-cholesterol (HDL-C), triglycerides (TG), and insulin (FI) was quantified. The technical error (TE) defined as the within-subject standard deviation derived from these measurements was computed. An adverse response for a given risk factor was defined as a change that was at least two TEs away from no change but in an adverse direction. Thus an adverse response was recorded if an increase reached 10 mm Hg or more for SBP, 0.42 mmol/L or more for TG, or 24 pmol/L or more for FI or if a decrease reached 0.12 mmol/L or more for HDL-C. Completers from six exercise studies were used in the present analysis: Whites (N = 473) and Blacks (N = 250) from the HERITAGE Family Study; Whites and Blacks from DREW (N = 326), from INFLAME (N = 70), and from STRRIDE (N = 303); and Whites from a University of Maryland cohort (N = 160) and from a University of Jyvaskyla study (N = 105), for a total of 1,687 men and women. Using the above definitions, 126 subjects (8.4%) had an adverse change in FI. Numbers of adverse responders reached 12.2% for SBP, 10.4% for TG, and 13.3% for HDL-C. About 7% of participants experienced adverse responses in two or more risk factors. CONCLUSIONS/SIGNIFICANCE: Adverse responses to regular exercise in cardiovascular and diabetes risk factors occur. Identifying the predictors of such unwarranted responses and how to prevent them will provide the foundation for personalized exercise prescription.

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Written from the paper’s full text.

TL;DR

Adverse metabolic responses to regular exercise—worsening of systolic blood pressure, HDL-cholesterol, triglycerides, or fasting insulin beyond measurement error—occur in a nontrivial minority of adults across six exercise studies. The paper estimates prevalences of roughly 8%–13% per risk factor and about 7% for two or more risk factors.

Key findings

Across six exercise studies (maximum N = 1,687), adverse responder prevalence was 8.3% for fasting insulin (abstract states 8.4%), 13.3% for HDL-C, 10.3% for triglycerides, and 12.2% for systolic blood pressure.
In HERITAGE, 6%–9% of Blacks and Whites experienced adverse responses for each of the four risk factors, with no substantive differences between ethnic groups.
About 7% of participants experienced adverse responses in two or more risk factors; Table 8 reports 6% with exactly two and 0.8% with three or four.
Adverse response traits appeared independent of cardiorespiratory fitness improvement: only 2 of 56 tested differences in VO2max gain between adverse and non-adverse responders reached p ≤ 0.05, far from a Bonferroni-adjusted p = 0.0009. DREW showed no substantive differences in adverse response prevalence across 4, 8, or 12 kcal/kg/week exercise doses.

Methods

Secondary analysis of completers from six exercise intervention studies: HERITAGE (473 Whites, 250 Blacks), DREW (326), INFLAME (70), STRRIDE (303), MARYLAND (160), and JYVASKYLA (105), for a maximum of 1,687 men and women.
Adverse response was defined as an exercise-induced change at least 2× the technical error (TE) in an adverse direction: increase ≥10 mm Hg for systolic BP, ≥0.42 mmol/L for triglycerides, ≥24 pmol/L for fasting insulin, or decrease ≤0.12 mmol/L for HDL-C. TE was derived from 60 subjects measured three times over 3 weeks, except fasting insulin, for which assays were performed twice and TE was estimated using other HERITAGE data plus literature.
Analyses included prevalence tabulations, paired t tests for within-cohort mean changes, general linear models comparing VO2max gains between adverse and non-adverse responders with age, sex, and baseline VO2max as covariates, and a DREW dose comparison.

Limitations

The paper states that the causes of adverse responses are unknown, that exercise-drug interactions cannot be directly tested with available data, and that it is unknown whether some adverse responders would revert with different exercise doses or modalities; findings also need extension to other risk factors such as LDL-cholesterol, inflammation markers, and adiposity traits.
Evident from the text: this is a secondary analysis of completers from heterogeneous studies with differing protocols and health statuses, some trait data are unavailable (e.g., STRRIDE systolic BP is N/A), and the fasting insulin TE was not based on three repeated measurements but estimated from other data and literature.

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Crossref · 10.1371/journal.pone.0037887

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 15 cited sources checked · 0 supported · 0 flagged

Findingown data
Adverse responses to regular exercise in cardiovascular and diabetes risk factors occur.
“Adverse responses to regular exercise in cardiovascular and diabetes risk factors occur.”
- Also stated in: § Discussion · plain
  “Thus, some individuals experience ARs when exposed to regular exercise, but the causes of the phenomenon are unknown at this time.”
Quote in the paperSubstantial claim
- Rests on an assumption: Completers of the six exercise studies are representative of sedentary adults generally.
Findingown data
Among the same 1,687 subjects, the prevalence of adverse responses reached 10.3%-10.4% for triglycerides.
“Numbers of adverse responders reached 12.2% for SBP, 10.4% for TG, and 13.3% for HDL-C.”
- Also stated in: § Results · plain
  “Based on a maximum of 1687 subjects, the prevalence of an AR reached 8.3% for the changes in FI, 13.3% for the changes in fasting HDL-C, 10.3% for TG, and 12.2% for resting SBP.”
Quote in the paperSubstantial claim
- Rests on an assumption: The technical error estimates derived from the HERITAGE ancillary study apply to the other five exercise studies.
- Rests on an assumption: The six exercise studies are sufficiently comparable to pool for estimating overall prevalence of adverse responses.
- Rests on an assumption: Attrition in the six studies did not bias the prevalence estimates of adverse responses.
Findingnone given
All gains in VO2max in the six cohorts were significant at p<0.05.
“All gains in VO2max are significant at p<0.05.”
Quote in the paperNot a substantial claim
Findingown data
Substantial numbers of subjects with or without medication in these cohorts experienced one or more adverse responses.
“Yet substantial numbers of subjects with or without medication in these cohorts experienced one or more ARs.”
Quote in the paperSubstantial claim
- Rests on an assumption: Medication use reported in the cohorts is accurate and does not confound the comparison of adverse response prevalence.
Findingown data
Only a small minority of participants (<1%) exhibited adverse responses for three or more traits.
“Only a small minority of participants (<1%) exhibited ARs for three or more traits.”
Quote in the paperSubstantial claim
- Rests on an assumption: The six exercise studies are sufficiently comparable to pool for estimating overall prevalence of adverse responses.
- Rests on an assumption: Attrition in the six studies did not bias the prevalence estimates of adverse responses.

Findingown data
The prevalence of adverse responses appears to be similar at low and high doses of exercise.
“The prevalence of ARs appears to be similar at low and high doses of exercise.”
- Also stated in: § Results · plain
  “No substantive differences were observed in the prevalence of ARs among the three levels of exercise energy expenditure, which ranged from 4 to 12 kcal/kg of body weight per week.”
Quote in the paperSubstantial claim
Findingown data
Among the same 1,687 subjects, the prevalence of adverse responses reached 12.2% for resting systolic blood pressure.
“Numbers of adverse responders reached 12.2% for SBP, 10.4% for TG, and 13.3% for HDL-C.”
- Also stated in: § Results · plain
  “Based on a maximum of 1687 subjects, the prevalence of an AR reached 8.3% for the changes in FI, 13.3% for the changes in fasting HDL-C, 10.3% for TG, and 12.2% for resting SBP.”
Quote in the paperSubstantial claim
- Rests on an assumption: The technical error estimates derived from the HERITAGE ancillary study apply to the other five exercise studies.
- Rests on an assumption: The six exercise studies are sufficiently comparable to pool for estimating overall prevalence of adverse responses.
- Rests on an assumption: Attrition in the six studies did not bias the prevalence estimates of adverse responses.
Findingown data
Among the same 1,687 subjects, the prevalence of adverse responses reached 13.3% for HDL-C.
“Numbers of adverse responders reached 12.2% for SBP, 10.4% for TG, and 13.3% for HDL-C.”
- Also stated in: § Results · plain
  “Based on a maximum of 1687 subjects, the prevalence of an AR reached 8.3% for the changes in FI, 13.3% for the changes in fasting HDL-C, 10.3% for TG, and 12.2% for resting SBP.”
Quote in the paperSubstantial claim
- Rests on an assumption: The technical error estimates derived from the HERITAGE ancillary study apply to the other five exercise studies.
- Rests on an assumption: The six exercise studies are sufficiently comparable to pool for estimating overall prevalence of adverse responses.
- Rests on an assumption: Attrition in the six studies did not bias the prevalence estimates of adverse responses.
Findingown data
The prevalence of adverse responses for select risk factors varied from 8.3% for fasting insulin to 13.3% for HDL-C.
“The prevalence of ARs for select risk factors varied from 8.3% for the exercise training-induced changes in FI to 13.3% for the changes in HDL-C, with about 7% of participants experiencing adverse changes in two or more risk factors.”
Quote in the paperSubstantial claim
Findingnone given
The presence of adverse responses was confirmed in five other exercise intervention studies beyond HERITAGE.
“Even though the presence of ARs was first detected among completers in Blacks and Whites of the HERITAGE Family Study, in which subjects were confirmed to be sedentary at baseline, with a rather healthy profile, the phenomenon was confirmed in five other exercise intervention studies.”
Quote in the paperSubstantial claim
Findingown data
Adverse response traits are independent of the improvement in cardiorespiratory fitness.
“These data indicate that AR traits are independent of the improvement in cardiorespiratory fitness.”
Quote in the paperSubstantial claim
Findingown data
About 7% of participants experienced adverse responses in two or more risk factors.
“About 7% of participants experienced adverse responses in two or more risk factors.”
- Also stated in: § Results · hedged
  “Approximately 7% of sedentary adults experienced ARs for at least two common cardiometabolic and diabetes risk factors following exposure to regular exercise.”
Quote in the paperSubstantial claim
- Rests on an assumption: Completers of the six exercise studies are representative of sedentary adults generally.
- Rests on an assumption: The six exercise studies are sufficiently comparable to pool for estimating overall prevalence of adverse responses.
- Rests on an assumption: Attrition in the six studies did not bias the prevalence estimates of adverse responses.
Study design and conductown data
The technical error (TE) for the risk factors was quantified from repeated measurements in 60 subjects over 3 weeks.
“Sixty subjects were measured three times over a period of three weeks, and variation in resting systolic blood pressure (SBP) and in fasting plasma HDL-cholesterol (HDL-C), triglycerides (TG), and insulin (FI) was quantified.”
- Also stated in: § Definition of adverse responses · plain
  “Sixty subjects were measured three times (except for FI) over a period of 3 weeks for each trait [15], [16], [17], [18], [19].”
Quote in the paperSubstantial claim0 of 3 sources checked
- cites [15] J Gagnon, 1996, The HERITAGE Family Study: Quality assurance and quality control., Ann Epidemiol source
- cites [16] JH Wilmore, 1997, Reproducibility of anthropometric and body composition measurements: the HERITAGE Family Study1., Int J Obes Relat Metab Disord source
- cites [17] JH Wilmore, 1998, Reproducibility of cardiovascular, respiratory, and metabolic responses to submaximal exercise: the HERITAGE Family Study., Med Sci Sports Exerc source
Interpretationown data
Adverse response traits are not explained by the amount of exercise imposed by the program.
“Moreover, the AR traits are not explained by prior health status of subjects, age, amount of exercise imposed by the program, or lack of improvement in cardiorespiratory fitness.”
Quote in the paperSubstantial claim
Interpretationown data
Based on analysis of the six studies, it is highly unlikely that adverse responses are the result of unwarranted exercise-drug interaction effects.
“The question cannot be answered with direct experimental data at the moment, but based on our analysis of the results of the six studies, it is highly unlikely that it is the case.”
Quote in the paperSubstantial claim
- Rests on an assumption: Medication use reported in the cohorts is accurate and does not confound the comparison of adverse response prevalence.
Interpretationown data
Adverse response traits are not explained by prior health status of subjects.
“Moreover, the AR traits are not explained by prior health status of subjects, age, amount of exercise imposed by the program, or lack of improvement in cardiorespiratory fitness.”
Quote in the paperSubstantial claim
Interpretationown data
The consistency in the prevalence of adverse responses across heterogeneous studies in terms of health status and exercise training regimen is notable.
“The consistency in the prevalence of ARs across heterogeneous studies in terms of health status of subjects at baseline and of exercise training regimen is notable.”
Quote in the paperSubstantial claim
Premisecitation
The response pattern to exercise training aggregates in families.
“Research based on HERITAGE has amply demonstrated that the response pattern to exercise training aggregates in families [25], [26], [27], 28.”
Quote in the paperSubstantial claim0 of 3 sources checked
- cites [25] C Bouchard, 1999, Familial aggregation of VO(2max) response to exercise training: results from the HERITAGE Family Study., J Appl Physiol source
- cites [26] T Rice, 2002, Familial aggregation of blood lipid response to exercise training in the health, risk factors, exercise training, and genetics (HERITAGE) Family Study., Circulation source
- cites [27] PT Katzmarzyk, 2000, Familial resemblance for coronary heart disease risk: the HERITAGE Family Study., Ethn Dis
Premisecitation
There is considerable interindividual variability in the ability to improve cardiorespiratory fitness and cardiometabolic and diabetes risk factor profile in response to regular exercise.
“However, there is considerable interindividual variability in the ability to improve one's cardiorespiratory fitness and cardiometabolic and diabetes risk factor profile in response to regular exercise. This clear finding of the HERITAGE Family Study has been replicated [3], [4], [5], [6].”
Quote in the paperSubstantial claim0 of 3 sources checked
- cites [3] C Bouchard, 2001, Individual differences in response to regular physical activity., Med Sci Sports Exerc source
- cites [4] NG Boule, 2005, Effects of exercise training on glucose homeostasis: The HERITAGE Family Study., Diabetes Care source
- cites [5] AS Leon, 2002, Variability in the response of HDL cholesterol to exercise training in the HERITAGE Family Study., Int J Sports Med source
Interpretationown data
Adverse response traits are not explained by age.
“Moreover, the AR traits are not explained by prior health status of subjects, age, amount of exercise imposed by the program, or lack of improvement in cardiorespiratory fitness.”
Quote in the paperSubstantial claim

May combine two claims. 6
The quote only partly states this claim. 1
Classified as probably not a substantial claim. 1

May combine two claims.
Findingown data
In HERITAGE, 6% to 9% of Blacks and Whites experienced adverse responses for each of the four risk factors, with no substantive differences between the two ethnic groups.
“Although HERITAGE subjects were apparently healthy and not taking medication for blood pressure, glucose, or lipid anomalies and were exposed to the same exercise program, 6% to 9% of Blacks and Whites experienced ARs for each of the four risk factors, with no substantive differences between the two ethnic groups.”
Quote in the paperSubstantial claim
The quote only partly states this claim.
Findingown data
Among 1,687 men and women from six exercise studies, 126 subjects (8.3%-8.4%) had an adverse change in fasting insulin.
“Using the above definitions, 126 subjects (8.4%) had an adverse change in FI.”
- Also stated in: § Results · plain
  “Based on a maximum of 1687 subjects, the prevalence of an AR reached 8.3% for the changes in FI, 13.3% for the changes in fasting HDL-C, 10.3% for TG, and 12.2% for resting SBP.”
Quote in the paperSubstantial claim
- Rests on an assumption: The technical error estimates derived from the HERITAGE ancillary study apply to the other five exercise studies.
- Rests on an assumption: The six exercise studies are sufficiently comparable to pool for estimating overall prevalence of adverse responses.
- Rests on an assumption: Attrition in the six studies did not bias the prevalence estimates of adverse responses.
May combine two claims.
Findingown data
The mean changes induced by the exercise programs were generally in the expected direction (decreases in fasting insulin, triglycerides, and systolic blood pressure and increases in HDL-C), with some statistically nonsignificant exceptions.
“The mean changes induced by the exercise programs were generally in the expected direction (i.e., decreases in FI, TG, and SBP and increases in HDL-C). There were, however, some statistically nonsignificant exceptions to these general trends.”
Quote in the paperNot a substantial claim
- Rests on an assumption: The four risk factors (systolic blood pressure, fasting insulin, HDL-cholesterol, and triglycerides) are valid indicators of cardiovascular and diabetes risk.
May combine two claims.
Findingown data
No evidence was found for differences in the prevalence of adverse responses between Blacks and Whites or between men and women.
“In summary, we did not find any evidence for differences in the prevalence of ARs between Blacks and Whites or between men and women.”
Quote in the paperSubstantial claim
Classified as probably not a substantial claim.
Study design and conductown data
For fasting insulin, the technical error was estimated using only two assays plus other HERITAGE data and observations from the literature.
“In the case of FI, the assays were performed only twice, and we used other HERITAGE data plus observations from the literature to develop an estimate of TE for FI (Information S1).”
Quote in the paperSubstantial claim
May combine two claims.
Premisecitation
The genetic component of a response trait can be defined in terms of RNA abundance observed in the sedentary state or by specific genomic variants.
“There are strong indications from a baseline skeletal muscle gene expression profile and from a genome-wide association study performed on the Whites of HERITAGE that the genetic component of a response trait can be defined in terms of RNA abundance observed in the sedentary state or by specific genomic variants [31], [32], [33].”
Quote in the paperSubstantial claim0 of 3 sources checked
- cites [31] C Bouchard, 2011, Genomic predictors of the maximal O uptake response to standardized exercise training programs., J Appl Physiol source
- cites [32] JA Timmons, 2010, Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans., J Appl Physiol source
- cites [33] T Rankinen, 2012, The heritability of submaximal exercise heart rate response to exercise training is accounted for by nine SNPs., J Appl Physiol source
May combine two claims.
Premisecitation
The heritability of exercise-induced changes reached about 30% for plasma HDL-C and triglycerides and about 20% to 25% for indicators of insulin metabolism and resting systolic blood pressure.
“In fact, the heritability of the changes induced by the exercise program reached about 30% for plasma HDL-C and TG [26] and about 20% to 25% for indicators of insulin metabolism and resting SBP [29], [30].”
Quote in the paperSubstantial claim0 of 3 sources checked
- cites [26] T Rice, 2002, Familial aggregation of blood lipid response to exercise training in the health, risk factors, exercise training, and genetics (HERITAGE) Family Study., Circulation source
- cites [29] P An, 2005, Genome-wide linkage scans for prediabetes phenotypes in response to 20 weeks of endurance exercise training in non-diabetic whites and blacks: the HERITAGE Family Study., Diabetologia source
- cites [30] T Rice, 2002, Heritability of HR and BP response to exercise training in the HERITAGE Family Study., Med Sci Sports Exerc source
May combine two claims.
Interpretationown data
Adverse responses for common cardiometabolic and diabetes risk factors are much more prevalent than acute exercise-related cardiac events and become evident with exposure to regular exercise.
“In contrast, ARs as defined herein for common cardiometabolic and diabetes risk factors are much more prevalent and become evident with exposure to regular exercise.”
Quote in the paperSubstantial claim

8 of 8

The paper relies on this without support.
Completers of the six exercise studies are representative of sedentary adults generally.
“Approximately 7% of sedentary adults experienced ARs for at least two common cardiometabolic and diabetes risk factors following exposure to regular exercise.”
The paper relies on this without support.
The technical error estimates derived from the HERITAGE ancillary study apply to the other five exercise studies.
“An ancillary study designed to quantify TE for several biological traits was undertaken in HERITAGE.”
“These AR definitions are used in the remainder of this report.”
The paper relies on this without support.
The six exercise studies are sufficiently comparable to pool for estimating overall prevalence of adverse responses.
“Based on a maximum of 1687 subjects, the prevalence of an AR reached 8.3% for the changes in FI, 13.3% for the changes in fasting HDL-C, 10.3% for TG, and 12.2% for resting SBP.”
The paper relies on this without support.
Attrition in the six studies did not bias the prevalence estimates of adverse responses.
“Completers from six exercise studies were used in the present analysis”
The paper relies on this without support.
The four risk factors (systolic blood pressure, fasting insulin, HDL-cholesterol, and triglycerides) are valid indicators of cardiovascular and diabetes risk.
“with a focus on exercise-induced changes in resting systolic blood pressure (SBP), fasting insulin (FI), HDL-cholesterol (HDL-C), and triglycerides (TG).”
The paper relies on this without support.
Medication use reported in the cohorts is accurate and does not confound the comparison of adverse response prevalence.
“many subjects in DREW, INFLAME, MARYLAND, and STRRIDE were taking medications for high blood pressure, hyperglycemia, or dyslipoproteinemia. Yet substantial numbers of subjects with or without medication in these cohorts experienced one or more ARs.”

6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

For 20% to 25% of participants undertaking an exercise programme there is little to no favourable response, while 5% to 10% have adverse events.
“It has been previously suggested that for 20% to 25% of participants undertaking an exercise programme there is little to no favourable response (Timmons 2014), while a small percentage (5% to 10%) have adverse events (Bouchard 2012).”
From Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews (2017) · cites this paper as Bouchard 2012
About 7-15% of individuals showed an adverse response in systolic blood pressure and fasting HDL cholesterol, triglycerides and insulin after chronic exercise.
“7–15% of individuals demonstrated an ‘adverse response’ regarding alterations in systolic blood pressure, as well as in fasting levels of HDL cholesterol, triglycerides and insulin25,26.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [26]
In humans, metabolic non-response or adverse responses to exercise have been described.
“Moreover, in humans, metabolic non-response or even adverse responses to exercise have been described26.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [26]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

Fasting-insulin adverse-response prevalence differs
Minor
The abstract reports 8.4% for fasting insulin, while the Results and Table 5 report 8.3% for the same 126 adverse responders.
Triglyceride adverse-response prevalence differs
Minor
The abstract reports 10.4% for triglycerides, while the Results and Table 5 report 10.3%.

2 of 2

Individual differences in response to regular physical activity
BOUCHARD, C., & RANKINEN, T. (2001) · Medicine and Science in Sports and Exercise · doi:10.1097/00005768-200106001-00013 · Cited by 939 · cited 1× · see citing works
“This clear finding of the HERITAGE Family Study has been replicated [3,4,5,6].”
BackgroundSelf-citation
Familial aggregation ofV˙ <scp>o</scp> 2 max response to exercise training: results from the HERITAGE Family Study
Bouchard, C., An, P., Rice, T., Skinner, J. S., Wilmore, J. H., Gagnon, J., Pérusse, L., Leon, A. S., & Rao, D. C. (1999) · Journal of Applied Physiology · doi:10.1152/jappl.1999.87.3.1003 · Cited by 875 · cited 1× · see citing works
“Research based on HERITAGE has amply demonstrated that the response pattern to exercise training aggregates in families [25,26,27,28].”
BackgroundSelf-citation
The Incidence of Primary Cardiac Arrest during Vigorous Exercise
Siscovick, D. S., Weiss, N. S., Fletcher, R. H., & Lasky, T. (1984) · New England Journal of Medicine · doi:10.1056/nejm198410043111402 · Cited by 838 · cited 1× · see citing works
“It is important to differentiate between ARs for risk factors for common chronic diseases, as referred to in the present study, from other more acute ARs such as cardiac events related to exertion during an exercise bout [20,21,22], sudden cardiac death during or immediately after exercise typically associated with a…”
Background
Effects of Different Doses of Physical Activity on Cardiorespiratory Fitness Among Sedentary, Overweight or Obese Postmenopausal Women With Elevated Blood Pressure: A Randomized Controlled Trial
Church, T. S., Earnest, C. P., Skinner, J. S., & Blair, S. N. (2007) · JAMA · doi:10.1001/jama.297.19.2081 · Cited by 756 · cited 2× · see citing works
“This clear finding of the HERITAGE Family Study has been replicated [3,4,5,6].”
BackgroundMethodSelf-citation
The Human Gene Map for Performance and Health-Related Fitness Phenotypes
Rankinen, T., Bray, M. S., Hagberg, J. M., Përusse, L., Roth, S. M., Wolfarth, B., & Bouchard, C. (2006) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000233789.01164.4f · Cited by 734 · see citing works
Self-citation
Cardiac arrest during long-distance running races
Kim, J. H., Malhotra, R., Chiampas, G., d'Hemecourt, P., Troyanos, C., Cianca, J., Smith, R. N., Wang, T. J., Roberts, W. O., Thompson, P. D., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1106468 · Cited by 597 · cited 1× · see citing works
“It is important to differentiate between ARs for risk factors for common chronic diseases, as referred to in the present study, from other more acute ARs such as cardiac events related to exertion during an exercise bout [20,21,22], sudden cardiac death during or immediately after exercise typically associated with a…”
Background
Genomic predictors of the maximal O2 uptake response to standardized exercise training programs
Bouchard, C., Sarzynski, M. A., Rice, T. K., Kraus, W. E., Church, T. S., Sung, Y. J., Rao, D. C., & Rankinen, T. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00973.2010 · Cited by 422 · cited 1× · see citing works
“There are strong indications from a baseline skeletal muscle gene expression profile and from a genome-wide association study performed on the Whites of HERITAGE that the genetic component of a response trait can be defined in terms of RNA abundance observed in the sedentary state or by specific genomic variants [31,3…”
BackgroundSelf-citation
Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans
Timmons, J. A., Knudsen, S., Rankinen, T., Koch, L. G., Sarzynski, M., Jensen, T., Keller, P., Scheele, C., Vollaard, N. B. J., Nielsen, S., et al. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01295.2009 · Cited by 358 · cited 1× · see citing works
“There are strong indications from a baseline skeletal muscle gene expression profile and from a genome-wide association study performed on the Whites of HERITAGE that the genetic component of a response trait can be defined in terms of RNA abundance observed in the sedentary state or by specific genomic variants [31,3…”
BackgroundSelf-citation
Effects of Exercise Training on Glucose Homeostasis
Boulé, N. G., Weisnagel, S. J., Lakka, T. A., Tremblay, A., Bergman, R. N., Rankinen, T., Leon, A. S., Skinner, J. S., Wilmore, J. H., Rao, D. C., et al. (2005) · Diabetes Care · doi:10.2337/diacare.28.1.108 · Cited by 356 · cited 1× · see citing works
“This clear finding of the HERITAGE Family Study has been replicated [3,4,5,6].”
BackgroundSelf-citation
The HERITAGE family study. Aims, design, and measurement protocol.
Bouchard, C., Leon, A. S., Rao, D. C., Skinner, J. S., Wilmore, J. H., & Gagnon, J. (1995) · PubMed · Cited by 331 · see citing works
Self-citation
Aims, design, and measurement protocol
BOUCHARD, C., LEON, A. S., RAO, D. C., SKINNER, J. S., WlLMORE, J. H., & GAGNON, J. (1995) · Medicine & Science in Sports & Exercise · doi:10.1249/00005768-199505000-00015 · Cited by 271 · cited 1× · see citing works
“HERITAGE (Health, Risk Factors, Exercise Training And Genetics) Family Study The sample, study design, and exercise training protocol of HERITAGE have been described elsewhere [7].”
MethodSelf-citation
Comparison of Aerobic Versus Resistance Exercise Training Effects on Metabolic Syndrome (from the Studies of a Targeted Risk Reduction Intervention Through Defined Exercise - STRRIDE-AT/RT)
Bateman, L. A., Slentz, C. A., Willis, L. H., Shields, A. T., Piner, L. W., Bales, C. W., Houmard, J. A., & Kraus, W. E. (2011) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2011.04.037 · Cited by 235 · cited 1× · see citing works
“Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) STRRIDE (84% Whites) includes two complementary studies [10,11].”
BackgroundSelf-citation
Studies of a targeted risk reduction intervention through defined exercise (STRRIDE).
Kraus, W., Torgan, C., Duscha, B., Norris, J., Brown, S. A., Cobb, F., Bales, C., Annex, B., Samsa, G., Houmard, J., et al. (2001) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-200110000-00025 · Cited by 161 · cited 1× · see citing works
“Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) STRRIDE (84% Whites) includes two complementary studies [10,11].”
BackgroundSelf-citation
Individual responses to combined endurance and strength training in older adults.
KARAVIRTA, L., HÄKKINEN, K., KAUHANEN, A., ARIJA-BLÁZQUEZ, A., SILLANPÄÄ, E., RINKINEN, N., & HÄKKINEN, A. (2011) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e3181f1bf0d · Cited by 139 · cited 1× · see citing works
“University of Jyväskylä Study (JYVASKYLA) Healthy, sedentary 40- to 67-year-old men and women were recruited [13].”
MethodSelf-citation
The human gene map for performance and health-related fitness phenotypes: the 2001 update
Rankinen, T., Përusse, L., Rauramaa, R., Rivera, M. A., Wolfarth, B., & Bouchard, C. (2002) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-200208000-00001 · Cited by 119 · cited 1× · see citing works
“It is important to differentiate between ARs for risk factors for common chronic diseases, as referred to in the present study, from other more acute ARs such as cardiac events related to exertion during an exercise bout [20,21,22], sudden cardiac death during or immediately after exercise typically associated with a…”
BackgroundSelf-citation
Variability in the Response of HDL Cholesterol to Exercise Training in the HERITAGE Family Study
Leon, A. S., Gaskill, S. E., Rice, T., Bergeron, J., Gagnon, J., Rao, D. C., Skinner, J. S., Wilmore, J. H., & Bouchard, C. (2002) · International Journal of Sports Medicine · doi:10.1055/s-2002-19270 · Cited by 116 · cited 1× · see citing works
“This clear finding of the HERITAGE Family Study has been replicated [3,4,5,6].”
BackgroundSelf-citation
Dose-Response to Exercise in Women Aged 45???75 yr (DREW): Design and Rationale
Morss, G. M., Jordan, A., Skinner, J. S., Dunn, A. L., Church, T. S., Earnest, C. P., Kampert, J. B., Jurča, R., & Blair, S. N. (2004) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000113738.06267.e5 · Cited by 110 · see citing works
Self-citation
Reproducibility of maximal exercise test data in the HERITAGE Family Study
Skinner, J. S., WILMORE, K. M., Jaskólska, A., Jaskólski, A., Daw, E. W., Rice, T., Gagnon, J., Leon, A. S., Wilmore, J. H., Rao, D. C., et al. (1999) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-199911000-00020 · Cited by 99 · cited 1× · see citing works
“Sixty subjects were measured three times (except for FI) over a period of 3 weeks for each trait [15,16,17,18,19].”
BackgroundSelf-citation
Selected body measurements of children 6-11 years.
Malina, R., Hamill, P., & Lemeshow, S. (1973) · Vital and health statistics. Series 11, Data from the National Health Survey · doi:10.1111/j.1753-4887.1973.tb05072.x · Cited by 87
Heritability of HR and BP response to exercise training in the HERITAGE Family Study
RICE, T., AN, P., GAGNON, J., LEON, A. S., SKINNER, J. S., WILMORE, J. H., BOUCHARD, C., & RAO, D. C. (2002) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-200206000-00011 · Cited by 83 · cited 8× · see citing works
“Numbers of adverse responders reached 12.2% for SBP, 10.4% for TG, and 13.3% for HDL-C.”
BackgroundInfluentialSelf-citation
Familial aggregation of blood lipid response to exercise training in the health, risk factors, exercise training, and genetics (HERITAGE) Family Study.
Rice, T., Després, J.-P., Pérusse, L., Hong, Y., Province, M. A., Bergeron, J., Gagnon, J., Leon, A. S., Skinner, J. S., Wilmore, J. H., et al. (2002) · Circulation · doi:10.1161/01.cir.0000014969.85364.9f · Cited by 65 · see citing works
Self-citation
Reproducibility of anthropometric and body composition measurements: the HERITAGE Family Study
Wilmore, J., Stanforth, P., Domenick, M., Gagnon, J., Daw, E., Leon, A., Rao, D., Skinner, J., & Bouchard, C. (1997) · International Journal of Obesity · doi:10.1038/sj.ijo.0800404 · Cited by 61 · see citing works
Self-citation
Reproducibility of cardiovascular, respiratory, and metabolic responses to submaximal exercise: The HERITAGE Family Study
WILMORE, J. H., STANFORTH, P. R., TURLEY, K. R., GAGNON, J., DAW, E. W., LEON, A. S., RAO, D. C., SKINNER, J. S., & BOUCHARD, C. (1998) · Medicine &amp Science in Sports &amp Exercise · doi:10.1097/00005768-199802000-00014 · Cited by 57 · cited 1× · see citing works
“Sixty subjects were measured three times (except for FI) over a period of 3 weeks for each trait [15,16,17,18,19].”
BackgroundSelf-citation
Genome-wide linkage scans for prediabetes phenotypes in response to 20 weeks of endurance exercise training in non-diabetic whites and blacks: the HERITAGE Family Study
An, P., Teran-Garcia, M., Rice, T., Rankinen, T., Weisnagel, S. J., Bergman, R. N., Boston, R. C., Mandel, S., Stefanovski, D., Leon, A. S., et al. (2005) · Diabetologia · doi:10.1007/s00125-005-1769-4 · Cited by 54 · cited 8× · see citing works
“Numbers of adverse responders reached 12.2% for SBP, 10.4% for TG, and 13.3% for HDL-C.”
BackgroundInfluentialSelf-citation
The HERITAGE Family Study: Quality assurance and quality control.
Gagnon, J. (1996) · Annals of Epidemiology · doi:10.1016/s1047-2797(96)00068-3 · Cited by 52 · cited 1× · see citing works
“Sixty subjects were measured three times (except for FI) over a period of 3 weeks for each trait [15,16,17,18,19].”
Background
Plasma post-heparin lipase activities in the HERITAGE family study: the reproducibility, gender differences, and associations with lipoprotein levels
Després, J., Gagnon, J., Bergeron, J., Couillard, C., Leon, A. S., Rao, D. C., Skinner, J. S., Wilmore, J. H., & Bouchard, C. (1999) · Clinical Biochemistry · doi:10.1016/s0009-9120(98)00106-4 · Cited by 48 · see citing works
Self-citation
Heritability of submaximal exercise heart rate response to exercise training is accounted for by nine SNPs
Rankinen, T., Sung, Y. J., Sarzynski, M. A., Rice, T. K., Rao, D. C., & Bouchard, C. (2012) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01287.2011 · Cited by 45 · see citing works
Self-citation
The effect of endurance exercise training on plasma lipoprotein AI and lipoprotein AI:AII concentrations in sedentary adults
Wilund, K. R., Colvin, P. L., Phares, D. A., Goldberg, A. P., & Hagberg, J. M. (2002) · Metabolism · doi:10.1053/meta.2002.33356 · Cited by 31 · cited 1× · see citing works
“University of Maryland Gene Exercise Research Study (MARYLAND) Briefly, 160 men and women (100% Whites) ages 50 to 75 years who were sedentary, nondiabetic, and nonsmoking, with no prior history of cardiovascular disease but with one National Cholesterol Education Program lipid abnormality or blood pressure in the pre…”
BackgroundSelf-citation
Selected body measurements of children 6-11 years.
(1973) · PubMed · Cited by 30 · see citing works
Athletes, athletics, and sudden cardiac death
THOMPSON, P. D. (1993) · Medicine & Science in Sports & Exercise · doi:10.1249/00005768-199309000-00001 · Cited by 24 · cited 1× · see citing works
“It is important to differentiate between ARs for risk factors for common chronic diseases, as referred to in the present study, from other more acute ARs such as cardiac events related to exertion during an exercise bout [20,21,22], sudden cardiac death during or immediately after exercise typically associated with a…”
Background
Exercise and Sudden Cardiac Death
Thompson, P. D., & Mitchell, J. H. (1984) · New England Journal of Medicine · doi:10.1056/nejm198410043111410 · Cited by 23 · cited 1× · see citing works
“It is important to differentiate between ARs for risk factors for common chronic diseases, as referred to in the present study, from other more acute ARs such as cardiac events related to exertion during an exercise bout [20,21,22], sudden cardiac death during or immediately after exercise typically associated with a…”
Background
Inflammation and exercise (INFLAME): Study rationale, design, and methods
Thompson, A. M., Mikus, C. R., Rodarte, R. Q., Distefano, B., Priest, E. L., Sinclair, E., Earnest, C. P., Blair, S. N., & Church, T. S. (2007) · Contemporary Clinical Trials · doi:10.1016/j.cct.2007.09.009 · Cited by 20 · cited 1× · see citing works
“0 mg/L) were randomized to an endurance exercise or a control group [9].”
MethodSelf-citation
Untitled work
(2000) · PubMed · Cited by 18 · see citing works
Self-citation
Familiality of triglyceride and LPL response to exercise training: the HERITAGE Study
Hong, Y., Rice, T., & Gagnon, J. (2000) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-200008000-00012 · Cited by 13 · cited 1× · see citing works
“Research based on HERITAGE has amply demonstrated that the response pattern to exercise training aggregates in families [25,26,27,28].”
Background

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Sorted by citations

Exercise Metabolism and the Molecular Regulation of Skeletal Muscle Adaptation
Egan, B., & Zierath, J. R. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.012 · Cited by 2,084 · see citing works
“…participants engage in carefully controlled exercise training regimens, the nature of the training response is remarkably heterogeneous, allowing the classification of non-, low, and high responders (Bouchard et al., 1999; Hubal et al., 2005), and even adverse responders (Bouchard et al., 2012).”
Background
International exercise recommendations in older adults (ICFSR): Expert consensus guidelines
Izquierdo, M., Merchant, R. A., Morley, J. E., Anker, S. D., Aprahamian, I., Arai, H., Aubertin-Leheudre, M., Bernabei, R., Cadore, E. L., Cesari, M., et al. (2021) · The Journal of nutrition, health and aging · doi:10.1007/s12603-021-1665-8 · Cited by 1,247 · see citing works
Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews
Geneen, L. J., Moore, R. A., Clarke, C., Martin, D., Colvin, L. A., & Smith, B. H. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011279.pub3 · Cited by 1,222 · see citing works
Exerkines in health, resilience and disease
Chow, L. S., Gerszten, R. E., Taylor, J. M., Pedersen, B. K., van Praag, H., Trappe, S., Febbraio, M. A., Galis, Z. S., Gao, Y., Haus, J. M., et al. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00641-2 · Cited by 927 · see citing works
Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews
Geneen, L. J., Moore, R. A., Clarke, C., Martin, D., Colvin, L. A., & Smith, B. H. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011279.pub2 · Cited by 719 · see citing works
Update on the effects of physical activity on insulin sensitivity in humans
Bird, S. R., & Hawley, J. A. (2017) · BMJ Open Sport & Exercise Medicine · doi:10.1136/bmjsem-2016-000143 · Cited by 646 · see citing works
Precision Nutrition: A Review of Personalized Nutritional Approaches for the Prevention and Management of Metabolic Syndrome
de Toro‐Martín, J., Arsenault, B. J., Després, J., & Vohl, M. (2017) · Nutrients · doi:10.3390/nu9080913 · Cited by 510 · see citing works
“have shown that besides the inter-individual variability in the beneficial response to a PA intervention regarding cardiovascular disease (CVD) and type 2 diabetes (T2D) risk factors, some individuals may even experience negative responses, such as a decrease in plasma HDL-C or an increase in systolic blood pressure,…”
Background
Exercise for Hypertension: A Prescription Update Integrating Existing Recommendations with Emerging Research
Pescatello, L. S., MacDonald, H. V., Lamberti, L., & Johnson, B. T. (2015) · Current Hypertension Reports · doi:10.1007/s11906-015-0600-y · Cited by 431 · see citing works
High responders and low responders: factors associated with individual variation in response to standardized training.
Mann, T. N., Lamberts, R. P., & Lambert, M. I. (2014) · Sports Medicine · doi:10.1007/s40279-014-0197-3 · Cited by 379 · see citing works
Effect of Physical Activity/Exercise on Oxidative Stress and Inflammation in Muscle and Vascular Aging
El Assar, M., Álvarez-Bustos, A., Sosa, P., Angulo, J., & Rodríguez-Mañas, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158713 · Cited by 371 · see citing works
“In fact, one study reported alterations in systolic blood pressure, HDL, triglycerides, and insulin levels [211].”
Background
Personality and physical activity: A systematic review and meta-analysis
Wilson, K. E., & Dishman, R. K. (2014) · Personality and Individual Differences · doi:10.1016/j.paid.2014.08.023 · Cited by 378 · see citing works
VO2max Trainability and High Intensity Interval Training in Humans: A Meta-Analysis
Bacon, A. P., Carter, R. E., Ogle, E. A., & Joyner, M. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073182 · Cited by 311 · see citing works
“3 L N min [47].”
There Are No Nonresponders to Resistance-Type Exercise Training in Older Men and Women
Churchward‐Venne, T. A., Tieland, M., Verdijk, L. B., Leenders, M., Dirks, M. L., de Groot, C. P. G. M., & van Loon, L. J. C. (2015) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2015.01.071 · Cited by 296 · see citing works
Biology of VO2max: looking under the physiology lamp
Lundby, C., Montero, D., & Joyner, M. (2017) · Acta Physiologica · doi:10.1111/apha.12827 · Cited by 300 · see citing works
Individual response to exercise training - a statistical perspective
Hecksteden, A., Kraushaar, J., Scharhag-Rosenberger, F., Theisen, D., Senn, S., & Meyer, T. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00714.2014 · Cited by 289 · see citing works
“In the meantime, “nonresponse” or even “adverse response” to regular physical exercise has been addressed by several authors (6, 7, 10, 30, 37, 39).”
Background
Precision exercise medicine: understanding exercise response variability
Ross, R., Goodpaster, B. H., Koch, L. G., Sarzynski, M. A., Kohrt, W. M., Johannsen, N. M., Skinner, J. S., Castro, A., Irving, B. A., Noland, R. C., et al. (2019) · British Journal of Sports Medicine · doi:10.1136/bjsports-2018-100328 · Cited by 292 · see citing works
Self-citation
Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained
Nokia, M. S., Lensu, S., Ahtiainen, J. P., Johansson, P. P., Koch, L. G., Britton, S. L., & Kainulainen, H. (2016) · The Journal of Physiology · doi:10.1113/jp271552 · Cited by 257 · see citing works
“For some, aerobic training provides substantial gain in maximal aerobic capacity (V̇O2 max) and metabolic health, whereas for others the same amount of training results in little or even negative change (Bouchard & Rankinen, 2001; see also Timmons, 2011; Bouchard et al. 2012).”
Background
Separate effects of intensity and amount of exercise on interindividual cardiorespiratory fitness response.
Ross, R., de Lannoy, L., & Stotz, P. J. (2015) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2015.07.024 · Cited by 224 · see citing works
Dose-Response Matters! - A Perspective on the Exercise Prescription in Exercise-Cognition Research
Herold, F., Müller, P., Gronwald, T., & Müller, N. G. (2019) · Frontiers in Psychology · doi:10.3389/fpsyg.2019.02338 · Cited by 196 · see citing works
Physical Activity as a Critical Component of First-Line Treatment for Elevated Blood Pressure or Cholesterol: Who, What, and How?: A Scientific Statement From the American Heart Association
Gibbs, B. B., Hivert, M., Jerome, G. J., Kraus, W. E., Rosenkranz, S. K., Schorr, E. N., Spartano, N. L., & Lobelo, F. (2021) · Hypertension · doi:10.1161/hyp.0000000000000196 · Cited by 198 · see citing works
Self-citation
Inter-individual variability in the adaptive responses to endurance and sprint interval training: a randomized crossover study.
Bonafiglia, J. T., Rotundo, M. P., Whittall, J. P., Scribbans, T. D., Graham, R. B., & Gurd, B. J. (2016) · PLOS ONE · doi:10.1371/journal.pone.0167790 · Cited by 172 · see citing works
Aerobic exercise but not resistance exercise reduces intrahepatic lipid content and visceral fat and improves insulin sensitivity in obese adolescent girls: a randomized controlled trial
Lee, S., Deldin, A. R., White, D., Kim, Y., Libman, I. M., Rivera-Vega, M., Kuk, J. L., Sandoval, S., Boesch, C., & Arslanian, S. A. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00285.2013 · Cited by 170 · see citing works
Do Non-Responders to Exercise Exist—and If So, What Should We Do About Them?
Pickering, C., & Kiely, J. (2019) · Sports Medicine · doi:10.1007/s40279-018-01041-1 · Cited by 165 · see citing works
Toward exercise as personalized medicine.
Buford, T. W., Roberts, M. D., & Church, T. S. (2013) · Sports Medicine · doi:10.1007/s40279-013-0018-0 · Cited by 158 · see citing works
Self-citation
Wellness Incentives In The Workplace: Cost Savings Through Cost Shifting To Unhealthy Workers
Horwitz, J. R., Kelly, B. D., & DiNardo, J. (2013) · Health Affairs · doi:10.1377/hlthaff.2012.0683 · Cited by 147 · see citing works
Exercise training for patients with type 2 diabetes and cardiovascular disease: What to pursue and how to do it. A Position Paper of the European Association of Preventive Cardiology (EAPC)
Kemps, H., Kränkel, N., Dörr, M., Moholdt, T. T., Wilhelm, M., Paneni, F., Serratosa, L., Solberg, E. E., Hansen, D., Halle, M., et al. (2019) · European Journal of Preventive Cardiology · doi:10.1177/2047487318820420 · Cited by 147 · see citing works
Heritability of objectively assessed daily physical activity and sedentary behavior
den Hoed, M., Brage, S., Zhao, J. H., Westgate, K. L., Nessa, A., Ekelund, U., Spector, T. D., Wareham, N. J., & Loos, R. J. F. (2013) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.113.069849 · Cited by 139 · see citing works
“Our findings have important consequences for public health initiatives, because adherence to a physical activity intervention program is likely more challenging for individuals who lack a biological drive to be active, and might even experience adverse effects in response to being physically active (47), than for indi…”
Background
Type 2 diabetes mellitus and exercise impairment
Reusch, J. E. B., Bridenstine, M., & Regensteiner, J. G. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-012-9234-4 · Cited by 137 · see citing works
“Most, but not all, participants in prospective exercise interventions improved their cardiovascular risk profiles with exercise interventions [27].”
Background
Cardiac rehabilitation fitness changes and subsequent survival
Schutter, A. D., Kachur, S. M., Lavie, C. J., Menezes, A. R., Shum, K. K., Bangalore, S., Arena, R. A., & Milani, R. V. (2018) · European Heart Journal - Quality of Care and Clinical Outcomes · doi:10.1093/ehjqcco/qcy018 · Cited by 155 · see citing works
Effects of short‐term endurance exercise on gut microbiota in elderly men
Taniguchi, H., Tanisawa, K., Sun, X., Kubo, T., Hoshino, Y., Hosokawa, M., Takeyama, H., & Higuchi, M. (2018) · Physiological Reports · doi:10.14814/phy2.13935 · Cited by 137 · see citing works
“Although regular aerobic exercise is effective for prevention and treatment of hypertension, considerable interindividual variability in the ability to improve blood pressure in response to exercise has been described (Bouchard et al. 2012).”
Background
Understanding the variation in exercise responses to guide personalized physical activity prescriptions
Noone, J., Mucinski, J. M., DeLany, J. P., Sparks, L. M., & Goodpaster, B. H. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2023.12.025 · Cited by 128 · see citing works
Sarcopenia: a potential cause and consequence of type 2 diabetes in Australia's ageing population?
Scott, D. S., de Courten, B. V., & Ebeling, P. R. (2016) · The Medical Journal of Australia · doi:10.5694/mja16.00446 · Cited by 119 · see citing works
N-acetylcysteine supplementation increases exercise performance and reduces oxidative stress only in individuals with low levels of glutathione
Paschalis, V., Theodorou, A. A., Margaritelis, N. V., Kyparos, A., & Nikolaidis, M. G. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.12.007 · Cited by 112 · see citing works
Heterogeneity of physical function responses to exercise training in older adults.
Chmelo, E. A., Crotts, C. I., Newman, J. C., Brinkley, T. E., Lyles, M. F., Leng, X., Marsh, A. P., & Nicklas, B. J. (2015) · Journal of the American Geriatrics Society · doi:10.1111/jgs.13322 · Cited by 110 · see citing works
“individuals who experience a negative response to regular exercise performance for certain outcomes.(23,24) In older adults, exercise training studies that show efficacy for improving functional ability often report main effects or mean group differences without expressing the extent of interindividual variability for…”
Background
Adaptations to endurance training depend on exercise‐induced oxidative stress: exploiting redox interindividual variability
Margaritelis, N., Theodorou, A., Paschalis, V., Veskoukis, A., Dipla, K., Zafeiridis, A., Panayiotou, G., Vrabas, I., Kyparos, A., & Nikolaidis, M. (2018) · Acta Physiologica · doi:10.1111/apha.12898 · Cited by 114 · see citing works
Repeated testing for the assessment of individual response to exercise training
Hecksteden, A., Pitsch, W., Rosenberger, F., & Meyer, T. (2018) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00896.2017 · Cited by 110 · see citing works
“This intuitive approach has been used in the seminal papers by Bouchard et al. (10, 12) but is also applied in more recent work (46).”
Method
Genomic and transcriptomic predictors of response levels to endurance exercise training
Sarzynski, M. A., Ghosh, S., & Bouchard, C. (2017) · The Journal of Physiology · doi:10.1113/jp272559 · Cited by 107 · see citing works
“If we use the gains in V̇O2max in millilitres O2 per minute as reported in the HERITAGE Family Study as a guide, a mean gain of about 400 ml O2 was achieved with a standard deviation (SD) of about 200 ml.”
ResultInfluentialSelf-citation
Performance Enhancement: What Are the Physiological Limits?
Lundby, C., & Robach, P. (2015) · Physiology · doi:10.1152/physiol.00052.2014 · Cited by 109 · see citing works
Can Exercise Teach Us How to Treat Heart Disease?
Mann, N., & Rosenzweig, A. (2012) · Circulation · doi:10.1161/circulationaha.111.060376 · Cited by 105 · see citing works
An overview of ischemic preconditioning in exercise performance: A systematic review
Caru, M., Lévesque, A., Lalonde, F. M., et al. (2019) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2019.01.008 · Cited by 103 · see citing works
“Indeed, it has been shown in healthy and untrained populations that there is a great interindividual variability in subjects’ capacity to improve their cardiac profile in response to regular exercise.(71) It has been hypothesized that the same situation exists for IPC, where there are both responders and nonresponders…”
Background
Incidence of V˙O2max Responders to Personalized versus Standardized Exercise Prescription
Weatherwax, R. M., HARRIS, N. K., Kilding, A. E., & Dalleck, L. C. (2018) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000001842 · Cited by 100 · see citing works
A Practical and Time-Efficient High-Intensity Interval Training Program Modifies Cardio-Metabolic Risk Factors in Adults with Risk Factors for Type II Diabetes
Phillips, B. E., Kelly, B. M., Lilja, M. R., Ponce‐González, J. G., Brogan, R. J., Morris, D. L., Gustafsson, T. P., Kraus, W. E., Atherton, P. J., Vollaard, N. B. J., et al. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00229 · Cited by 98 · see citing works
Self-citation
The effects of exercise on the lipoprotein subclass profile: A meta-analysis of 10 interventions
Sarzynski, M. A., Burton, J. H., Rankinen, T., Blair, S. N., Church, T. S., Després, J., Hagberg, J. M., Landers‐Ramos, R. Q., Leon, A. S., Mikus, C. R., et al. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.10.018 · Cited by 99 · see citing works
Self-citation
Resistance to the Beneficial Effects of Exercise in Type 2 Diabetes: Are Some Individuals Programmed to Fail?
Stephens, N. A., & Sparks, L. M. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-2545 · Cited by 97 · see citing works
“Conclusions In an exhaustive review by Bouchard et al (107), the authors call for more large-scale clinical exercise intervention studies to advance the field of “exercise as medicine.””
Background
Effects and prevalence of nonresponders after 12 weeks of high-intensity interval or resistance training in women with insulin resistance: a randomized trial
Álvarez, C., Ramírez‐Campillo, R., Ramírez‐Vélez, R., & Izquierdo, M. (2017) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01037.2016 · Cited by 96 · see citing works
“In brief, studies have used terms such as low/high responders (12), nonresponders/responders (30), and adverse response (4) among other terms.”
Background
Inter-Individual Responses of Maximal Oxygen Uptake to Exercise Training: A Critical Review
Williamson, P., Atkinson, G., & Batterham, A. M. (2017) · Sports Medicine · doi:10.1007/s40279-017-0680-8 · Cited by 96 · see citing works
Incidence of nonresponse and individual patterns of response following sprint interval training
Gurd, B. J., Giles, M. D., Bonafiglia, J. T., Raleigh, J. P., Boyd, J. C., Ma, J. K., Zelt, J. G. E., & Scribbans, T. D. (2016) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2015-0449 · Cited by 92 · see citing works
“Recently, more critical approaches to determining cut-points for identifying nonresponders that consider both biological and technical error, and should minimize the risk of misidentifying responders as nonresponders and vis versa, have been proposed (Hopkins 2000; Bouchard et al. 2012).”
BackgroundMethodInfluential
Recommendations in Post-exercise Hypotension: Concerns, Best Practices and Interpretation
Brito, L. C., Fecchio, R. Y., Peçanha, T., Andrade-Lima, A., Halliwill, J. R., & Forjaz, C. L. M. (2019) · International Journal of Sports Medicine · doi:10.1055/a-0938-4415 · Cited by 94 · see citing works
“However, similar to debates deriving from randomized control trials, there is still no consensus on how to define a true “response”: whether it should be based on the presence of clinically relevant change [116] or on clearly measurable change [117].”
Background
Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes
Malin, S. K., Haus, J. M., Solomon, T. P. J., Blaszczak, A., Kashyap, S. R., & Kirwan, J. P. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00441.2013 · Cited by 89 · see citing works
“Reductions in HDL might be considered an adverse response to exercise, and prior work has suggested that familial heritability in part explains the intersubject HDL variability in response to exercise (9).”
Background
The relationship between skeletal muscle mitochondrial citrate synthase activity and whole body oxygen uptake adaptations in response to exercise training.
Vigelsø, A., Andersen, N. B., & Dela, F. (2014) · Europe PMC (PubMed Central) · Cited by 96 · see citing works
Personalized, Evidence-Informed Training Plans and Exercise Prescriptions for Performance, Fitness and Health
Wackerhage, H., & Schoenfeld, B. J. (2021) · Sports Medicine · doi:10.1007/s40279-021-01495-w · Cited by 96 · see citing works
Pancreatic β-cell Function Is a Stronger Predictor of Changes in Glycemic Control After an Aerobic Exercise Intervention Than Insulin Sensitivity
Solomon, T. P. J., Malin, S. K., Karstoft, K., Kashyap, S. R., Haus, J. M., & Kirwan, J. P. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2232 · Cited by 87 · see citing works
Exercise training and artery function in humans: nonresponse and its relationship to cardiovascular risk factors
GREEN, D. J., Eijsvogels, T. M. H., Bouts, Y. M., Maiorana, A., Naylor, L. H., Scholten, R. R., Spaanderman, M. E. A., Pugh, C. J. A., Sprung, V. S., Schreuder, T. H. A., et al. (2014) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00354.2014 · Cited by 86 · see citing works
THE ANTIHYPERTENSIVE EFFECTS OF AEROBIC VERSUS ISOMETRIC HANDGRIP RESISTANCE EXERCISE
Ash, G. I., Taylor, B., Thompson, P. D., Macdonald, H. V., Lamberti, L. M., Chen, M.-H., Farinatti, P., Kraemer, W. J., Panza, G., Zaleski, A. L., et al. (2017) · Journal of Hypertension · doi:10.1097/hjh.0000000000001176 · Cited by 79 · see citing works
“One factor that can partially account for variability in the BP response to exercise is technical error related to obtaining repeated measurements [48].”
Going retro: Oxidative stress biomarkers in modern redox biology
Margaritelis, N. V., Cobley, J. N., Paschalis, V., Veskoukis, A. S., Theodorou, A. A., Kyparos, A., & Nikolaidis, M. G. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.02.005 · Cited by 84 · see citing works
Exercise-induced changes in inflammatory processes: Implications for thrombogenesis in cardiovascular disease
Chen, Y., Apostolakis, S. Z., & Lip, G. Y. H. (2014) · Annals of Medicine · doi:10.3109/07853890.2014.927713 · Cited by 83 · see citing works
Inter-individual variability in response to exercise intervention or usual care in hospitalized older adults
Sáez de Asteasu, M. L., Martínez‐Velilla, N., Zambom‐Ferraresi, F., Casas‐Herrero, Á., Cadore, E. L., Ramirez‐Velez, R., & Izquierdo, M. (2019) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12481 · Cited by 82 · see citing works
TGF-β Contributes to Impaired Exercise Response by Suppression of Mitochondrial Key Regulators in Skeletal Muscle
Böhm, A., Hoffmann, C., Irmler, M., Schneeweiß, P., Schnauder, G., Sailer, C., Schmid, V., Hudemann, J., Machann, J., Schick, F., et al. (2016) · Diabetes · doi:10.2337/db15-1723 · Cited by 79 · see citing works
The association between leisure time physical activity and coronary heart disease among men with different physical work demands: a prospective cohort study
Clays, E., Bacquer, D. D., Janssens, H., et al. (2013) · European Journal of Epidemiology · doi:10.1007/s10654-013-9764-4 · Cited by 78 · see citing works
“It was recently shown that adverse responses in cardiometabolic risk factors to regular exercise are not uncommon, and that predictors should be identified [25].”
Background
Exercise and diabetes: relevance and causes for response variability
Böhm, A., Weigert, C., Staiger, H., & Häring, H. (2015) · Endocrine · doi:10.1007/s12020-015-0792-6 · Cited by 79 · see citing works
Exercise in type 2 diabetes: genetic, metabolic and neuromuscular adaptations. A review of the evidence
Zanuso, S., Sacchetti, M., Sundberg, C. J., Orlando, G., Benvenuti, P., & Balducci, S. (2017) · British Journal of Sports Medicine · doi:10.1136/bjsports-2016-096724 · Cited by 78 · see citing works
Effects of exercise on resting blood pressure in obese children: a meta‐analysis of randomized controlled trials
García‐Hermoso, A., Saavedra, J. M., & Escalante, Y. (2013) · Obesity Reviews · doi:10.1111/obr.12054 · Cited by 82 · see citing works
The effect of Tai Chi and Qigong practice on depression and anxiety symptoms: A systematic review and meta-regression analysis of randomized controlled trials
Yin, J., & Dishman, R. K. (2014) · Mental health and physical activity · doi:10.1016/j.mhpa.2014.08.001 · Cited by 78 · see citing works
i-CONTENT tool for assessing therapeutic quality of exercise programs employed in randomised clinical trials
Hoogeboom, T. J., Kousemaker, M. C., van Meeteren, N. L., Howe, T., Bo, K., Tugwell, P., Ferreira, M., de Bie, R. A., van den Ende, C. H., & Stevens-Lapsley, J. E. (2021) · British Journal of Sports Medicine · doi:10.1136/bjsports-2019-101630 · Cited by 76 · see citing works
Understanding the individual responsiveness to resistance training periodization
Prestes, J., da Cunha Nascimento, D., Tibana, R. A., Teixeira, T. G., Vieira, D. C. L., Tajra, V., de Farias, D. L., Silva, A. O., Funghetto, S. S., de Souza, V. C., et al. (2015) · AGE · doi:10.1007/s11357-015-9793-x · Cited by 73 · see citing works
“2014), plasma fasting insulin, plasma triglycerides, and plasma high density-lipoprotein variables (Bouchard et al. 2012).”
Background
Promoting resilience in The face of ageing and disease: The central role of exercise and physical activity
Izquierdo, M., & Fiatarone Singh, M. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101940 · Cited by 70 · see citing works
Sources of Inter-individual Variability in the Therapeutic Response of Blood Glucose Control to Exercise in Type 2 Diabetes: Going Beyond Exercise Dose
Solomon, T. P. J. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00896 · Cited by 72 · see citing works
Near‐normalization of glycaemic control with glucagon‐like peptide‐1 receptor agonist treatment combined with exercise in patients with type 2 diabetes
Mensberg, P., Nyby, S., Jørgensen, P. G., Storgaard, H., Jensen, M. T., Sivertsen, J., Holst, J. J., Kiens, B., Richter, E. A., Knop, F. K., et al. (2016) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12797 · Cited by 68 · see citing works
The gene SMART study: method, study design, and preliminary findings
Yan, X., Eynon, N., Papadimitriou, I. D., Kuang, J., Munson, F., Tirosh, O., O’Keefe, L., Griffiths, L. R., Ashton, K. J., Byrne, N. M., et al. (2017) · BMC Genomics · doi:10.1186/s12864-017-4186-4 · Cited by 64 · see citing works
“This means some people are ‘low/medium responders’ (with limited improvements following exercise training), while others are ‘high-responders’ [5].”
Background
Changes in aerobic capacity and glycaemic control in response to reduced-exertion high-intensity interval training (REHIT) are not different between sedentary men and women
Metcalfe, R. S., Tardif, N., Thompson, D., & Vollaard, N. B. J. (2016) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2016-0253 · Cited by 68 · see citing works
Acute blood pressure changes are related to chronic effects of resistance exercise in medicated hypertensives elderly women
Moreira, S. R., Cucato, G. G., Terra, D. F., & Ritti‐Dias, R. M. (2014) · Clinical Physiology and Functional Imaging · doi:10.1111/cpf.12221 · Cited by 68 · see citing works
“…of RE and after the resistance training programme, some patients increased in BP. Adverse response to exercise, a condition defined as an exercise-induced change that worsens a risk factor, has been previously described and is known to affect approximately 10% of subjects (Bouchard et al., 2012).”
Background
The Relationship between the Blood Pressure Responses to Exercise following Training and Detraining Periods
Moker, E., Bateman, L. A., Kraus, W. E., & Pescatello, L. S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0105755 · Cited by 65 · see citing works
“[13] consolidated the findings from six large exercise training studies that included STRRIDE-AT/RT to examine the variability in the response of cardiometabolic risk factors to exercise training.”
BackgroundInfluentialSelf-citation
Lifestyle genomics and the metabolic syndrome: A review of genetic variants that influence response to diet and exercise interventions
Fenwick, P. H., Jeejeebhoy, K. N., Dhaliwal, R., Royall, D., Brauer, P. M., Tremblay, A., Klein, D., & Mutch, D. M. (2018) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2018.1437022 · Cited by 64 · see citing works
Advances in Exercise, Fitness, and Performance Genomics in 2015
Sarzynski, M. A., Loos, R. J. F., Lucía, A., Përusse, L., Roth, S. M., Wolfarth, B., Rankinen, T., & Bouchard, C. (2016) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000982 · Cited by 65 · see citing works
Self-citation
Exercise genomics—a paradigm shift is needed: a commentary
Bouchard, C. (2015) · British Journal of Sports Medicine · doi:10.1136/bjsports-2015-095294 · Cited by 63 · see citing works
Self-citation
The HERITAGE family study: a review of the effects of exercise training on cardiometabolic health, with insights into molecular transducers
SARZYNSKI, M. A., RICE, T. K., DESPRÉS, J.-P., PÉRUSSE, L., TREMBLAY, A., STANFORTH, P. R., TCHERNOF, A., BARBER, J. L., FALCIANI, F., CLISH, C., et al. (2022) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000002859 · Cited by 62 · see citing works
Self-citation
Exercise Dose, Exercise Adherence, and Associated Health Outcomes in the TIGER Study
Miller, F. L., O’Connor, D. P., Herring, M. P., Sailors, M. H., Jackson, A. S., Dishman, R. K., & Bray, M. S. (2013) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e3182a038b9 · Cited by 64 · see citing works
“Recent research has provided evidence that up to 7% of individuals exposed to physical activity may actually experience deleterious health outcomes (3).”
The independent and combined effects of exercise training and reducing sedentary behavior on cardiometabolic risk factors
Keadle, S. K., Lyden, K. A., STAUDENMAYER, J. W., Hickey, A., Viskochil, R. H., Braun, B., & Freedson, P. S. (2014) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2013-0379 · Cited by 65 · see citing works
“Cardiometabolic response to exercise training is highly variable (Bouchard et al. 2012; Melanson et al. 2013; Thomas et al. 2012), which increases the sample needed to detect a significant difference between groups.”
Background
Selectively bred rat model system for low and high response to exercise training
Koch, L. G., Pollott, G. E., & Britton, S. L. (2013) · Physiological Genomics · doi:10.1152/physiolgenomics.00021.2013 · Cited by 60 · see citing works
Concepts About V˙O2max and Trainability Are Context Dependent
Joyner, M. J., & Lundby, C. (2018) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000150 · Cited by 61 · see citing works
Looking Ahead Perspective: Where Will the Future of Exercise Biology Take Us?
Zierath, J. R., & Wallberg‐Henriksson, H. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.06.015 · Cited by 58 · see citing works
Skeletal Muscle PGC1α −1 Nucleosome Position and −260 nt DNA Methylation Determine Exercise Response and Prevent Ectopic Lipid Accumulation in Men
Bajpeyi, S., Covington, J. D., Taylor, E. M., Stewart, L. K., Galgani, J. E., & Henagan, T. M. (2017) · Endocrinology · doi:10.1210/en.2017-00051 · Cited by 59 · see citing works
Advances in Exercise, Fitness, and Performance Genomics in 2012
Përusse, L., Rankinen, T., Hagberg, J. M., Loos, R. J. F., Roth, S. M., Sarzynski, M. A., Wolfarth, B., & Bouchard, C. (2013) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e31828b28a3 · Cited by 58 · see citing works
“This sense of urgency is fueled by a recent article which provided evidence that some individuals exhibit adverse responses to regular exercise in cardiovascular disease and diabetes risk factors (3).”
Self-citation
Individual cardiovascular responsiveness to work-matched exercise within the moderate- and severe-intensity domains
Maturana, F. M., Schellhorn, P., Erz, G., Burgstahler, C., Widmann, M., Munz, B., Soares, R. N., Murias, J. M., Thiel, A., & Niess, A. M. (2021) · European Journal of Applied Physiology · doi:10.1007/s00421-021-04676-7 · Cited by 56 · see citing works
Fitness and strength responses to distinct exercise modes in twins: Studies of Twin Responses to Understand Exercise as a THerapy (STRUETH) study
Marsh, C. E., Thomas, H. J., Naylor, L. H., Scurrah, K. J., & GREEN, D. J. (2020) · The Journal of Physiology · doi:10.1113/jp280048 · Cited by 55 · see citing works
“Despite this, recent studies suggest that up to 20–30% of individuals may fail to exhibit beneficial physiological responses to exercise interventions that accord with guideline recommendations for health (Bouchard et al. 2012).”
Background
New Insights into Molecular Mechanisms Mediating Adaptation to Exercise; A Review Focusing on Mitochondrial Biogenesis, Mitochondrial Function, Mitophagy and Autophagy
Roberts, F. L., & Markby, G. R. (2021) · Cells · doi:10.3390/cells10102639 · Cited by 53 · see citing works
Safety and Efficacy of Aerobic Training in Patients With Cancer Who Have Heart Failure: An Analysis of the HF-ACTION Randomized Trial
Jones, L. W., Douglas, P. S., Khouri, M. G., Mackey, J. R., WOJDYLA, D. M., Kraus, W. E., Whellan, D. J., & O’Connor, C. M. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.53.5724 · Cited by 54 · see citing works
Self-citation
Contribution of central and peripheral adaptations to changes in maximal oxygen uptake following 4 weeks of sprint interval training
Raleigh, J. P., Giles, M. D., Islam, H., Nelms, M. W., Bentley, R. F., Jones, J. H., Neder, J. A., Boonstra, K. M., Quadrilatero, J., Simpson, C. A., et al. (2018) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2017-0864 · Cited by 54 · see citing works
A Systematic Review Examining the Approaches Used to Estimate Interindividual Differences in Trainability and Classify Individual Responses to Exercise Training
Bonafiglia, J. T., Preobrazenski, N., & Gurd, B. J. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.665044 · Cited by 59 · see citing works
Positive, limited and negative responders: The variability in physical fitness adaptation to basic military training
Burley, S. D., Drain, J. R., Sampson, J. A., & Groeller, H. (2018) · Journal of science and medicine in sport · doi:10.1016/j.jsams.2018.06.018 · Cited by 51 · see citing works
Exercise, Physical Activity, and Cardiometabolic Health
Belanger, M. J., Rao, P., & Robbins, J. (2021) · Cardiology in Review · doi:10.1097/crd.0000000000000417 · Cited by 60 · see citing works
“Notably, exercise produces a wide range in the magnitude of triglyceride reduction,(66) and as many as 10% of individuals will have a paradoxical increase in triglycerides after regular exercise.(67) A recent analysis from the HERITAGE Stduy identified a small number of single-nucleotide polymorphisms that explain a m…”
Background
Prevalence of Non-responders for Glucose Control Markers after 10 Weeks of High-Intensity Interval Training in Adult Women with Higher and Lower Insulin Resistance
Álvarez, C., Ramírez‐Campillo, R., Ramírez‐Vélez, R., & Izquierdo, M. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00479 · Cited by 51 · see citing works
Effects of 6-Weeks High-Intensity Interval Training in Schoolchildren with Insulin Resistance: Influence of Biological Maturation on Metabolic, Body Composition, Cardiovascular and Performance Non-responses
Álvarez, C., Ramírez‐Campillo, R., Ramírez‐Vélez, R., & Izquierdo, M. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00444 · Cited by 49 · see citing works
“…are mainly expressed in terms of the “mean,” but there is wide interindividual variability in response to exercise training (IVRET) that has not been fully clarified in adults (Sisson et al., 2009; Bouchard et al., 2012; Álvarez et al., 2017b; Montero and Lundby, 2017) and not explored in children.”
BackgroundInfluential
Blood pressure response to resistance training in hypertensive and normotensive older women
Nascimento, D. D. C., da Silva, C. R., Valduga, R., Saraiva, B., Neto, I. V. D. S., Vieira, A., Funghetto, S. S., Silva, A. D. O., Oliveira, S. D. C., Pereira, G. B., et al. (2018) · Clinical Interventions in Aging · doi:10.2147/cia.s157479 · Cited by 48 · see citing works
“Although, mechanisms for the lack of responsiveness are unknown, the present study reinforces the suggestions of Bouchard et al, and further research is required to clarify the potential molecular mechanisms that may account for the lack of improvement in BP from an RT program.(5) Between the possible mechanisms invol…”
Influential
Moderate‐ and High‐Intensity Exercise Improves Lipoprotein Profile and Cholesterol Efflux Capacity in Healthy Young Men
Stanton, K., Kienzle, V., Dinnes, D. L. M., Kotchetkov, I., Jessup, W., Kritharides, L., Celermajer, D. S., & Rye, K. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.121.023386 · Cited by 48 · see citing works
Current issues in the identification and treatment of metabolically healthy but obese individuals
Plourde, G., & Karelis, A. D. (2014) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2013.12.002 · Cited by 48 · see citing works
Theoretical and Biological Evaluation of the Link between Low Exercise Capacity and Disease RiskPreprint
Koch, L. G., & Britton, S. L. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029868 · Cited by 47 · see citing works
“Of recent interest are reports showing that there is wide variation for response to exercise training whereby some individuals experience no improvement (or even declines), whereas others show large gains (Vollaard et al. 2009; Timmons et al. 2010; Keller et al. 2011; Timmons 2011; Bouchard et al. 2012).”
Background
Association of skeletal muscle and serum metabolites with maximum power output gains in response to continuous endurance or high-intensity interval training programs: The TIMES study – A randomized controlled trial
Castro, A., Duft, R. G., Ferreira, M. L. V., de Andrade, A. L. L., Gáspari, A. F., Silva, L. D. M., Nunes, S. G. D. O., Cavaglieri, C. R., Ghosh, S., Bouchard, C., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0212115 · Cited by 47 · see citing works
Self-citation
Is high-intensity interval cycling feasible and more beneficial than continuous cycling for knee osteoarthritic patients? Results of a randomised control feasibility trial
Keogh, J. W., Grigg, J., & Vertullo, C. J. (2018) · PeerJ · doi:10.7717/peerj.4738 · Cited by 45 · see citing works
“Adverse events were defined as ‘an exercise-induced change that worsens an aspect of your condition that is greater than expected day-to-day variation,’ a definition very similar to that used previously in the study of 1,687 men and women undergoing exercise programs (Bouchard et al., 2012).”
Result
Physical Activity Enhances Metabolic Fitness Independently of Cardiorespiratory Fitness in Marathon Runners
Laye, M. J., Nielsen, M. B., Hansen, L. S., Knudsen, T. A., & Pedersen, B. K. (2015) · Disease Markers · doi:10.1155/2015/806418 · Cited by 45 · see citing works
“The HERITAGE study showed that between 8% and 13% of exercise intervention participants have worse off risk factors following 20 weeks to 6 months of exercise training programs [42].”
Method

Exogenous Glucocorticoids and a High-Fat Diet Cause Severe Hyperglycemia and Hyperinsulinemia and Limit Islet Glucose Responsiveness in Young Male Sprague-Dawley Rats
Beaudry, J. L., D'souza, A. M., Teich, T., Tsushima, R. G., & Riddell, M. C. (2013) · Endocrinology · doi:10.1210/en.2012-2114 · Cited by 44 · see citing works
The Effect of Fasting on Tissue Cyclic cAMP and Plasma Glucagon in the Obese Hyperglycemic Mouse
VINE, R. L. L., Voyles, N. R., Perrino, P. V., & Recant, L. (1975) · Endocrinology · doi:10.1210/endo-97-3-615 · Cited by 38 · see citing works
Modulation of Adipoinsular Axis in Prediabetic Zucker Diabetic Fatty Rats by Diazoxide
Alemzadeh, R., & Tushaus, K. (2004) · Endocrinology · doi:10.1210/en.2003-1523 · Cited by 38 · see citing works
Mechanisms of Impaired Growth Hormone Secretion in Genetically Obese Zucker Rats: Roles of Growth Hormone-Releasing Factor and Somatostatin*
TANNENBAUMt, G. S., Lapointe, M., Gurd, W., & Finkelstein, J. A. (1990) · Endocrinology · doi:10.1210/endo-127-6-3087 · Cited by 72 · see citing works
Growth hormone binding protein in the rat: effects of gonadal steroids
Carmignac, D. F., Gabrielsson, B. G., & Robinson, I. C. A. F. (1993) · Endocrinology · doi:10.1210/endo.133.6.8243263 · Cited by 68 · see citing works

Authors: Bouchard, C., Blair, S. N., Church, T. S., Earnest, C. P., Hagberg, J. M., Häkkinen, K., Jenkins, N. T., Karavirta, L., Kraus, W. E., Leon, A. S., Rao, D. C., Sarzynski, M. A., Skinner, J. S., Slentz, C. A., & Rankinen, T.
Affiliations: Pennington Biomedical Research Center (US)
University of South Carolina (US)
University of Maryland, College Park (US)
University of Jyväskylä (FI)
Duke Medical Center (US)
University of Minnesota (US)
Washington University in St. Louis (US)
Indiana University Bloomington (US)
Corresponding author: Bouchard, Claude
ORCID: Bouchard, Claude
Blair, Steven N.
Church, Timothy S.
Earnest, Conrad P.
Hagberg, James M.
Jenkins, Nathan T.
Karavirta, Laura
Kraus, William E.
Rao, D. C.
Sarzynski, Mark A.
Skinner, James S.
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2012-05-30
Volume: 7
Issue: 5
Pages: e37887
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0037887
PMC: PMC3364277
OpenAlex: W2085568044
Cited by: 389
References: 33
Citations by year: 2026: 9 · 2025: 15 · 2024: 20 · 2023: 12 · 2022: 21 · 2021: 35 · 2020: 22 · 2019: 41 · 2018: 40 · 2017: 37 · 2016: 27 · 2015: 25 · 2014: 31 · 2013: 46 · 2012: 5
FWCI: 20.30
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
PubMed (publishedVersion)
Jyväskylä University Digital Archive (University of Jyväskylä) (acceptedVersion, cc-by)
Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
Europe PMC (PubMed Central) (submittedVersion, cc-by)
PubMed Central (submittedVersion, cc-by)
Scholar Commons (University of South Carolina) (submittedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
IUScholarWorks (Indiana University) (submittedVersion, cc-by)
Topics: Health Sciences › Medicine › Physiology › Physical Activity and Health
Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: diabetes risk factors, fasting insulin, systolic blood pressure, HDL cholesterol, triglycerides, within-person variability, exercise prescription, racial differences
MeSH terms: Adult, Aged, Basal Metabolism, Blood Pressure, Cardiovascular Diseases, Diabetes Mellitus, Exercise Therapy

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Adverse metabolic response to regular exercise: is it a rare or common occurrence?

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