Adverse Metabolic Response to Regular Exercise: Is it a Rare or Common Occurrence

For more information, contact our Media Relations Manager, Ted Griggs, 225-763-2862 or our Communications Director, Lisa Stansbury, at 225-763-2978. Our news email box is also available at

Released: Wednesday, May 30, 2012

By Claude Bouchard, PhD; Steven N. Blair, PED; Timothy S. Church, MD, MPH, PhD; Conrad P. Earnest, PhD; James M. Hagberg, PhD; Keijo Häkkinen, PhD; Nathan T. Jenkins, PhD; Laura Karavirta, PhD; William E. Kraus, MD; Arthur S. Leon, MS, MD; D.C. Rao, PhD; Mark A. Sarzynski, PhD; James S. Skinner, PhD; Cris A. Slentz, PhD; and Tuomo Rankinen, PhD, PLoS ONE, 2012

BATON ROUGE, LA - Physical activity level and cardiorespiratory fitness are strongly and inversely associated with the risk of cardiovascular-, metabolic-, and aging-related morbidities, as well as premature death. However, there is considerable interindividual variability in the ability to improve one's fitness and cardiovascular and diabetes risk factor profile in response to regular exercise. Whether there are people who experience adverse changes in cardiovascular and diabetes risk factors from regular exercise has never been examined.

Addressing this issue for the first time, this new report demonstrates that a significant fraction of sedentary adults develop one or more adverse responses when they exercise regularly. The analysis is based on peer-reviewed data from six exercise intervention studies. The report focuses on the changes induced by the exercise program in resting systolic blood pressure, fasting insulin, high-density lipoprotein-cholesterol, and triglycerides. Completers from the following exercise intervention studies were used: 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.

The study defines "adverse response" as an exercise-induced change that worsens a risk factor beyond measurement error and expected day-to-day variation. To identify the threshold defining adverse responses, the authors relied on data from 60 subjects who had been measured three times over a period of three weeks as part of the HERITAGE Family Study protocol. These data were used to quantify intra-individual variation in resting systolic blood pressure and in fasting plasma high-density lipoprotein-cholesterol, triglycerides, and insulin. 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 standard deviations away from no change but in an adverse direction. For example, an adverse response for resting systolic blood pressure was recorded if an increase reached 10 mm Hg or more.

The authors found that percentages of adverse responders reached 8.4% for fasting insulin, 10.4% for triglycerides, 12.2% for systolic blood pressure, and 13.3% for high-density lipoprotein-cholesterol. Moreover, as many as 7% registered adverse responses for at least two cardiovascular or diabetes risk factors. This subgroup of multiple adverse responses appears to be particularly at risk of experiencing significant undesirable effects from regular exercise.

Very importantly, adverse responses could not be explained by age, gender, ethnicity, the level of cardiorespiratory fitness prior to exercise programs, the volume or intensity of exercise programs, the increase in cardiorespiratory fitness induced by exercise programs, or whether participants were using medication.

These observations have considerable implications for adults who are trying to maintain normal blood pressure, blood lipid, or blood sugar levels through a healthy diet and regular exercise, as a minority of these participants are likely to experience adverse responses such as those described in this report. These observations also have implications for therapeutic and rehabilitation programs such as those commonly used in cardiac rehabilitation and in type 2 diabetes treatment.

The challenge is now to identify predictors of adverse responses among sedentary people contemplating becoming physically active so that they are screened early and offered alternative approaches to modifying cardiometabolic risk factors if such a course of action is deemed appropriate. Predicting for a given individual the extent of benefits that can be expected from regular exercise or the risk of maladaptive reactions will be a cornerstone of personalized exercise medicine.

Despite the new findings reported today, one should remember that the overall benefits of regular exercise on adiposity, cardiovascular fitness, diabetes prevention, other common chronic disease prevention, and life expectancy greatly outweigh the risk of adverse responses in a minority of individuals.

The study was led by Dr. Claude Bouchard from the Pennington Biomedical Research Center with the collaboration of several other investigators at leading institutions in the United States and Finland. They include other investigators from Pennington Biomedical Research Center (Drs. TS Church, CP Earnest, MA Sarzynski, and T Rankinen), Duke University (Drs. WE Kraus and CA Slentz), University of Maryland (Drs. JM Hagberg and NT Jenkins), University of South Carolina (Dr. SN Blair), the University of Jyväskylä (Drs. K Häkkinen and L Karavirta), the University of Minnesota (Dr. AS Leon), Indiana University (Dr. JS Skinner), and Washington University School of Medicine (Dr. DC Rao).


The Pennington Biomedical Research Center is at the forefront of medical discovery as it relates to understanding the triggers of obesity, diabetes, cardiovascular disease, cancer and dementia. It is a campus of Louisiana State University and conducts basic, clinical and population research. The research enterprise at Pennington Biomedical includes approximately 80 faculty and more than 25 post-doctoral fellows who comprise a network of 44 laboratories supported by lab technicians, nurses, dietitians, and support personnel, and 13 highly specialized core service facilities. Pennington Biomedical's more than 500 employees perform research activities in state-of-the-art facilities on the 222-acre campus located in Baton Rouge, Louisiana.