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Hyperactive Autonomic Nervous System In Patients With Breast Cancer May Cause Fatigue And Aging

Researcher Janice Kiecolt-GlaserThe persistent fatigue that plagues one out of every three breast cancer survivors may be caused by one part of the autonomic nervous system running in overdrive, while the other part fails to slow it down.  That imbalance of a natural system in the body appears linked to the tiredness and exhaustion that can burden cancer patients as much as a decade after their successful treatment.

The effect is so great, researchers say, that it may be a sign of accelerated aging in fatigued patients, causing them to seem as much as 20 years older compared with patients who are not fatigued.

Those new research findings, just reported in the journalPsychoneuroendocrinology, are the latest from a three-decade-long study of the impact that stress can have on the human body.

Christopher Fagundes, a postdoctoral fellow at Ohio State University’s Institute of Behavioral Medicine Research (IBMR), and Janice Kiecolt-Glaser, a professor of psychiatry and psychology and a member of the IBMR, drew early data from a larger ongoing study testing whether yoga can combat continuing fatigue in breast cancer patients.

They were looking for a new biomarker, a signal that could point to the initial cause of this fatigue. Their target was the autonomic nervous system, that part of the body that controls unconscious activities like breathing, heartbeat, digestion and such, which earlier research had indicated might play a role.

The autonomic nervous system has two main parts – the sympathetic and the parasympathetic. The former is responsible for what has become known as the fight-or-flight response, a triggering of short-term, energized activity. The latter deals with opposite situations. It is the resting phase, best recognized by the sleepiness that may follow eating a big meal.

While the sympathetic system is an energy hog, the parasympathetic conserves energy, and the two should remain in balance in healthy individuals. The researchers were looking for differences between fatigued and non-fatigued cancer survivors.

“We started looking for biomarkers for cancer-related fatigue,” Fagundes said. “Other research has indicated that a systemic inflammation through the body might be a reliable biomarker for this.

“Sick people with inflammation become tired and lethargic, which makes sense since their bodies are using energy to fight off infections. You can imagine that a long-term, systemic inflammation, year-in and year-out, might produce this fatigue.”

For the study, 109 women participated and were placed in one of two groups – those who reported long-term fatigue and those who didn’t. The women varied from being two months to two years after being treated for their disease.

Fatigue is a normal response to breast cancer treatments like chemotherapy and radiation therapy, but one-third or more of breast cancer survivors report continued debilitating fatigue long after treatment has ended.

After a short relaxation period, each woman had blood drawn to establish a baseline level for norepinephrine, a stress hormone that served as an indicator of activity by the sympathetic nervous system.

Each participant had to give a five-minute speech before a two-person panel and then do a series of verbal arithmetic problems aimed at increasing stress levels. Additional blood samples were taken immediately after the stressor and then a half-hour later.

The norepinephrine levels rose as expected from the baseline in both groups after the stressful episode but the researchers were surprised to see something different. Regardless of the stressor, women who had persistent fatigue showed higher levels of norepinephrine than those who were not fatigued.

“They had higher sympathetic activity and lower parasympathetic activity,” Fagundes said, an indication that other researchers have suggested is a signal for inflammation.

The researchers also gauged another measure in the study, the natural variability in heart rate which decreases as a person ages. A lessened heart rate variability (HRV) is also an indicator of activity in the parasympathetic, or “resting,” system.

“People who were fatigued had weaker parasympathetic activity than those who weren’t,” he said.

“One of the things we know best is that exercise can enhance a person’s HRV,” Kiecolt-Glaser said. “Exercise is also the best documented treatment for fatigue, so this all begins to make sense.

“Fatigue isn’t a symptom that should be ignored. It’s a marker for other things that might be going on,” she said. Higher norepinephrine levels and lower HRV have been linked to high blood pressure, myocardial infarctions, strokes, and diabetes.

“When a cancer patient reports persistent fatigue following treatment, it is something that deserves attention. It may be a symptom of other things that matter.”

Working with Fagundes and Kiecolt-Glaser on the work were William Malarkey, Charles Shapiro, David Murray, Beom Seuk Hwang, Jean Philippe Gouin and Julian Thayer, all from Ohio State; and John Sollers from the University of Auckland.

Material adapted from Ohio State University.

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4 Responses to Hyperactive Autonomic Nervous System In Patients With Breast Cancer May Cause Fatigue And Aging

  1. avatar
    Christopher Fisher, PhD April 9, 2011 at 7:48 AM #

    I am hopeful our in-house expert on dysautonmia, Stephen Elliot, might have a comment or two about these findings.

  2. avatar
    Stephen Elliott April 9, 2011 at 9:30 AM #


    Thank you for the invitation to comment…

    Heart rate variability (HRV) is accepted as a very good indicator of autonomic status where diminished HRV is generally indicative of sympathetic overdrive, particularly where stress is a presenting symptom.

    HRV “tends to” decline with age at about 10% per decade (See R. DeMeersman,
    American Heart Journal, Volume 125, Number 3, March 1993). Numerous physiological markers including peak athletic performance, energy production, hormone production, resting blood oxygen level, and working blood oxygen level decline at this same rate. This decline begins at age 20. (The New Science Of Breath – 2nd Edition, Elliott & Edmonson, 2006).

    However, probably the most important biomarker that is not discussed is diaphragm range of movement, which we find to be the key determinant of the amplitude of the blood wave that issues from and returns to the lungs with each cycle of respiration, and via baroreceptor action, the key determinant of heart rate variability, heart rate variability falling as the blood wave rises in the arterial tree coincident with exhalation and rising as the blood wave falls in the arterial tree and rises in in the venous tree during inhalation.

    Visit the link to view the Valsalva Wave recorded at the earlobe:

    This wave – termed the “Valsalva Wave” rising and falling alternately in the arterial and venous circulation when we breathe results from the body’s elegant coordination of breathing, blood flow, and heart rate/output, and vascular capacity. (See for more information about the Valsalva Wave phenomenon and its relationship to heart rate variability. It is also discussed in detail in Coherent Breathing – The Definitive Method, Elliott & Edmonson, 2008.)

    In our work, we find that the declination of HRV with age is merely a tendency – not unlike the tendency to loose muscle mass as we age. The fundamental reason HRV tends to decline is that diaphragm range of movement tends to decline. The reason why this happens I consider to be one of the most important health questions
    of our time. However, through breathing intervention, specifically learning to breathe in such a way that the wave is produced, HRV increases and can be sustained at youthful levels will into maturity.

    There is a strong body of evidence correlating diminished HRV with stress, tension, anxiety, depression, hypertension, and numerous other maladies relating to sympathetic overdrive. In our work, we find that these maladies tend to
    diminish as breathing becomes more effective, HRV being a key indicator of breathing efficacy. To find out more about the science of Coherent Breathing please visit:

    • avatar
      Christopher Fisher, PhD April 9, 2011 at 9:45 AM #

      Thanks you Steve for your in-depth, interesting, and expert comment. I would not expect anything less from you, and the very reason I invited you to make a comment on this topic.

      I agree completely with your comments. I am strong advocate of this technique and most of my patients are trained in HRV. The more I learn about the importance of diaphragmatic breathing and the science behind it, the more I am amazed at how little attention the importance of proper breathing receives in our current healthcare system.

  3. avatar
    Stephen Elliott April 9, 2011 at 3:35 PM #

    Thanks Chris,

    I realize that I failed to mention that bio-energetic production is literally dependent on respiration. Regarding fatigue, if one’s breathing is suppressed, one cannot expect to feel vital and energetic. Consequently, breathing MUST be “righted” before fatigue can be overcome.


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