BKBetsy A. Keller

Betsy A. Keller

*This is an algorithmically generated author record based on publicly available information.

Betsy A. Keller has a total of 30 co-authors. Here are the top co-authors by number of shared publications:


Latest Publications

  • Open Access

    Cardiopulmonary and metabolic responses during a 2-day CPET in myalgic encephalomyelitis/chronic fatigue syndrome: translating reduced oxygen consumption to impairment status to treatment considerations

    by Betsy Keller, Candace N. Receno, Carl J. Franconi, Sebastian Harenberg, Jared Stevens, Xiangling Mao, Staci R. Stevens, Geoff Moore, Susan Levine, John Chia, et al.

    Background: Post-exertional malaise (PEM), the hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), represents a constellation of abnormal responses to physical, cognitive, and/or emotional exertion including profound fatigue, cognitive dysfunction, and exertion intolerance, among numerous other maladies. Two sequential cardiopulmonary exercise tests (2-d CPET) provide objective evidence of abnormal responses to exertion in ME/CFS but validated only in studies with small sample sizes. Further, translation of results to impairment status and approaches to symptom reduction are lacking. Methods: Participants with ME/CFS (Canadian Criteria; n = 84) and sedentary controls (CTL; n = 71) completed two CPETs on a cycle ergometer separated by 24 h. Two-way repeated measures ANOVA compared CPET measures at rest, ventilatory/anaerobic threshold (VAT), and peak effort between phenotypes and CPETs. Intraclass correlations described stability of CPET measures across tests, and relevant objective CPET data indicated impairment status. A subset of case–control pairs (n = 55) matched for aerobic capacity, age, and sex, were also analyzed. Results: Unlike CTL, ME/CFS failed to reproduce CPET-1 measures during CPET-2 with significant declines at peak exertion in work, exercise time, $$\dot{\text{V}}$$ V ˙ e, $$\dot{\text{V}}$$ V ˙ O2, $$\dot{\text{V}}$$ V ˙ CO2, $$\dot{\text{V}}$$ V ˙ T, HR, O2pulse, DBP, and RPP. Likewise, CPET-2 declines were observed at VAT for $$\dot{\text{V}}$$ V ˙ e/ $$\dot{\text{V}}$$ V ˙ CO2, PetCO2, O2pulse, work, $$\dot{\text{V}}$$ V ˙ O2 and SBP. Perception of effort (RPE) exceeded maximum effort criteria for ME/CFS and CTL on both CPETs. Results were similar in matched pairs. Intraclass correlations revealed greater stability in CPET variables across test days in CTL compared to ME/CFS owing to CPET-2 declines in ME/CFS. Lastly, CPET-2 data signaled more severe impairment status for ME/CFS compared to CPET-1. Conclusions: Presently, this is the largest 2-d CPET study of ME/CFS to substantiate impaired recovery in ME/CFS following an exertional stressor. Abnormal post-exertional CPET responses persisted compared to CTL matched for aerobic capacity, indicating that fitness level does not predispose to exertion intolerance in ME/CFS. Moreover, contributions to exertion intolerance in ME/CFS by disrupted cardiac, pulmonary, and metabolic factors implicates autonomic nervous system dysregulation of blood flow and oxygen delivery for energy metabolism. The observable declines in post-exertional energy metabolism translate notably to a worsening of impairment status. Treatment considerations to address tangible reductions in physiological function are proffered. Trial registration number: ClinicalTrials.gov, retrospectively registered, ID# NCT04026425, date of registration: 2019-07-17.


  • Open Access

    Recovery from Exercise in Persons with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

    by Geoffrey E. Moore, Betsy A. Keller, Jared Stevens, Xiangling Mao, Staci R. Stevens, John K. Chia, Susan M. Levine, Carl J. Franconi, Maureen R. Hanson

    Background and Objectives: Post-exertional malaise (PEM) is the hallmark of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but there has been little effort to quantitate the duration of PEM symptoms following a known exertional stressor. Using a Symptom Severity Scale (SSS) that includes nine common symptoms of ME/CFS, we sought to characterize the duration and severity of PEM symptoms following two cardiopulmonary exercise tests separated by 24 h (2-day CPET). Materials and Methods: Eighty persons with ME/CFS and 64 controls (CTL) underwent a 2-day CPET. ME/CFS subjects met the Canadian Clinical Criteria for diagnosis of ME/CFS; controls were healthy but not participating in regular physical activity. All subjects who met maximal effort criteria on both CPETs were included. SSS scores were obtained at baseline, immediately prior to both CPETs, the day after the second CPET, and every two days after the CPET-1 for 10 days. Results: There was a highly significant difference in judged recovery time (ME/CFS = 12.7 ± 1.2 d; CTL = 2.1 ± 0.2 d, mean ± s.e.m., Chi2 = 90.1, p < 0.0001). The range of ME/CFS patient recovery was 1–64 days, while the range in CTL was 1–10 days; one subject with ME/CFS had not recovered after one year and was not included in the analysis. Less than 10% of subjects with ME/CFS took more than three weeks to recover. There was no difference in recovery time based on the level of pre-test symptoms prior to CPET-1 (F = 1.12, p = 0.33). Mean SSS scores at baseline were significantly higher than at pre-CPET-1 (5.70 ± 0.16 vs. 4.02 ± 0.18, p < 0.0001). Pharmacokinetic models showed an extremely prolonged decay of the PEM response (Chi2 > 22, p < 0.0001) to the 2-day CPET. Conclusions: ME/CFS subjects took an average of about two weeks to recover from a 2-day CPET, whereas sedentary controls needed only two days. These data quantitate the prolonged recovery time in ME/CFS and improve the ability to obtain well-informed consent prior to doing exercise testing in persons with ME/CFS. Quantitative monitoring of PEM symptoms may provide a method to help manage PEM.


  • Open Access

    Plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis/chronic fatigue syndrome

    by Arnaud Germain, Ludovic Giloteaux, Geoffrey E. Moore, Susan M. Levine, John K. Chia, Betsy A. Keller, Jared Stevens, Carl J. Franconi, Xiangling Mao, Dikoma C. Shungu, et al.

    Post-exertional malaise (PEM) is a hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We monitored the evolution of 1157 plasma metabolites in 60 ME/CFS (45 female, 15 male) and 45 matched healthy control participants (30 female, 15 male) before and after 2 maximal cardiopulmonary exercise test (CPET) challenges separated by 24 hours, with the intent of provoking PEM in patients. Four time points allowed exploration of the metabolic response to maximal energy-producing capacity and the recovery pattern of participants with ME/CFS compared with the healthy control group. Baseline comparison identified several significantly different metabolites, along with an enriched percentage of yet-to-be identified compounds. Additionally, temporal measures demonstrated an increased metabolic disparity between cohorts, including unknown metabolites. The effects of exertion in the ME/CFS cohort predominantly highlighted lipid-related as well as energy-related pathways and chemical structure clusters, which were disparately affected by the first and second exercise sessions. The 24-hour recovery period was distinct in the ME/CFS cohort, with over a quarter of the identified pathways statistically different from the controls. The pathways that are uniquely different 24 hours after an exercise challenge provide clues to metabolic disruptions that lead to PEM. Numerous altered pathways were observed to depend on glutamate metabolism, a crucial component of the homeostasis of many organs in the body, including the brain.


  • Open Access

    A Pair of Identical Twins Discordant for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Differ in Physiological Parameters and Gut Microbiome Composition

    by Ludovic Giloteaux, Maureen R. Hanson, Betsy A. Keller

    BACKGROUND:Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with profound fatigue, flu-like symptoms, pain, cognitive impairment, orthostatic intolerance, and post-exertional malaise (PEM), and exacerbation of some or...


  • Open Access

    Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO2peak indicates functional impairment

    by Betsy A Keller, John L Pryor, Ludovic Giloteaux

    Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multi-system illness characterized, in part, by increased fatigue following minimal exertion, cognitive impairment, poor recovery to physical and other stressors, in addition to other symptoms. Unlike healthy subjects and other diseased populations who reproduce objective physiological measures during repeat cardiopulmonary exercise tests (CPETs), ME/CFS patients have been reported to fail to reproduce results in a second CPET performed one day after an initial CPET. If confirmed, a disparity between a first and second CPET could serve to identify individuals with ME/CFS, would be able to document their extent of disability, and could also provide a physiological basis for prescribing physical activity as well as a metric of functional impairment.


  • State of the Art Reviews: Development of Fitness in Children: The Influence of Gender and Physical Activity

    by Betsy A. Keller

    The influences of gender and physical activity on the development of fitness are reviewed from early childhood to late adolescence. Changes in parameters of fitness prior to puberty are driven predominantly by neuroendocrine-mediated factors, although physical activity level may be influenced largely by sociocultural factors prior to and following puberty. Thus, it is still unclear to what extent environment versus genetics accounts for gender differences in fitness. Future studies need to account for all factors known to explain gender differences in fitness to better differentiate intrinsic versus environmental causes. Consequently, one must consider if and to what extent a gender comparison study actually reveals true, inherent gender differences compared with sociocultural and/or cultural influences. Nevertheless, differences in fitness between girls and boys that are influenced by sociocultural factors should be considered when devising programs to promote physical activity and enhance fitness in youth. Fundamentally, the role of parents and primary caregivers in modeling physical activity and influencing the fitness level of their child cannot be overestimated.


  • Transcutaneous electrical muscle stimulation does not alter regional arm adiposity and muscularity

    by B.A. Keller, F.I. Katch

    The present study evaluated the effects of an electrical muscle stimulation (EMS) training protocol claimed to elicit site-specific fat reduction and muscle hypertrophy. The protocol includes 6 weeks (3 sessions/week, 10 contractions/session) of high frequency (2500 Hz) transcutaneous EMS training on upper arm muscle and fat tissue. Two groups of 10 subjects were stimulated either on the dominant biceps brachii (B) or triceps brachii (T). The non-dominant arm served as a control. Post-training measures of upper arm fat and muscle tissue evaluated with girths, skinfolds, and ultrasound measures of fat did not change following EMS training of the treatment and control arms (p > 0.05). Upper arm x-ray measurements to estimate total upper arm volume, muscle plus bone volume, and fat volume also did not change significantly for groups B and T following training (p > 0.05). The results thus indicate no selective upper arm muscle hypertrophy or site-specific fat reduction with high frequency EMS training of healthy muscle. Am. J Hum. Biol. 10:317–326, 1998.