Shorts

Exercise, Clock Genes, and Sleep

Yujiro Yamanaka and colleagues found that the time of day that exercise takes place changes its effect on the autonomic nervous system. The Japanese research team enrolled 22 healthy, young males for their study; seven acted as the control group, seven randomized into a morning exercise group, and eight were in the evening exercise group. Participants lived in a facility under dim light conditions (10 lux measured from the forehead), ate three meals at set times, and followed a strict sleeping schedule: “To adjust the sleep-wake cycle among the subjects in reference to the circadian cycle, the times of retiring to bed and wake-up were fixed in such a way that the retirement time should be 4 h before the melatonin peak and sleep length should be 8 h.” Blood samples, from an indwelling catheter in the forearm, were taken hourly during the first and last 24 hours and every two hours for the remainder of the study to examine the circadian peak phase of plasma melatonin. During the 16-hour waking period, participants filled out a questionnaire and took a performance test on the computer every two hours. Smoking, napping, and physical exercise (unless scheduled) were prohibited by all participants, but they could read books, watch videos, and listen to music.

Beginning on day three, participants in the exercise groups performed interval exercise with a bicycle ergometer for two hours. The morning group began to exercise three hours after waking, and the evening group began exercising 10 hours after waking. This schedule continued through day 6.

The researchers found that heart rate (HR) significantly increased during sleep in the evening exercisers, but not in the morning exercisers: “Since HR is stimulated by the sympathetic nerve activation, the evening exercise may continuously stimulate the sympathetic nervous system several hours after physical exercise.” In contrast, morning exercise significantly increased heart frequency during sleep, indicating increased cardiac parasympathetic activity. “The present results lead us to the hypothesis that although physical exercise stimulates, in general, the sympathetic nervous system, the activity of autonomic nervous system changed afterward depending on the time lapse,” the authors write. This study indicates that morning exercise improves the quality of nighttime sleep (and healing) by increasing parasympathetic nerve activity.

Yamanaka et al suggest that the autonomic nervous system itself might be responsible for the time-dependent effect of physical exercise. However, it may also be linked to the ‘clock genes’ in muscle tissue. Although the primary circadian pacemaker resides in the hypothalamus, organs throughout the body—including skeletal muscle—have clock and clock-controlled genes that display circadian rhythms. “Physical exercise is a nonphotic stimulus that can realign the skeletal muscle circadian system to the central clock, imposing a new rhythm at the organism level,” write Gerardo Gabriel Mirizio and colleagues. “This effect may be crucial to prevent or ameliorate diseases and disorders caused by disruptions of circadian rhythms.”

In their 2018 review article, Mirizio et al cite animal studies that show clock-gene expression increases with physical activity. Not only does this gene expression affect circadian rhythm, it also affects muscle function and metabolism: “Given that skeletal muscle is an essential tissue for energy metabolism homeostasis, it is not surprising that skeletal muscle circadian activity and metabolic processes are closely integrated.” Chronic circadian disruptions are linked to altered lipid profiles and/or insulin resistance. Understanding how the clock genes work and the role of physical activity is an on-going process. But scheduled physical exercise early in the day may improve sleep quality—and it will do no harm.

Mirizio GG, et al. the Impact of Physical Exercise on the Skeletal Muscle Clock Genes. Kinesiology. 2018;50 Suppl.1:5-18.

Yamanaka Y, et al. Morning and evening physical exercise differentially regulate the autonomic nervous system during nocturnal sleep in humans. Am J Physiol Regul Integr Comp Physiol. 2015;309:R1112-R1121.

Tools for Addressing Pain

Katinka van der Merwe, DC, specializes in helping people with complex regional pain syndrome (CRPS). She views people with CRPS and related conditions, such as reflex sympathetic dystrophy (RSD), as being “stuck in sympathetic overdrive” with the parasympathetic arm of the autonomic system being underactive. In a 2016 blog post, van der Merwe outlines three techniques—spinal manipulation, frequency specific microcurrent, and Quantum Neurology®–she uses in her practice to improve tone and function of the vagus nerve, the primary parasympathetic cranial nerve. Low vagal tone causes inflammation and problems with immune function, digestion, and sleep. Several factors can contribute to poor vagal function, including neck and/or tailbone injuries, toxicity, infections, emotional stress, and genetic factors.

First, Dr. van der Merwe uses spinal manipulation to remove pressure from the vagus nerve. The procedure typically needs to be repeated multiple times over a ten-week period in order for ligaments in the upper cervical spine to learn the correct position. Spinal manipulation to correct vertebral subluxations (dislocations) that put pressure on nerves can improve heart rate variability (HRV), according to a 2017 review article. HRV is a marker for autonomic nervous system health and adaptability and indicates the balance between the sympathetic and parasympathetic systems.

Frequency Specific Microcurrent (FSM), using a device that applies minuscule electric currents, is the second technique. Animal experiments have shown that microcurrents can increase protein synthesis and energy production, but the amperage must be very small. Whereas direct current, between 100 and 500 µamps, applied to rat skin increased ATP levels 300% -500%, current over 5,000 µamps caused ATP production to decline, compared to untreated controls.

Carolyn McMakin, DC, and George Douglas, DC, identified specific frequencies and developed a system for treating multiple conditions, including CRPS and fibromyalgia. Dr. McMakin wrote a 2010 article for The Pain Practitioner, based on her clinical experiences, in which she described the use of FSM to reduce neuropathic pain and increase range of motion. An earlier study involving people with fibromyalgia associated with spine trauma showed that FSM significantly reduced inflammatory cytokines, including IL-1, IL-6, TNF-α, and substance P, and increased endorphins—along with decreasing pain.

McMakin uses 40Hz on one channel and 396 Hz on the second channel to reduce neuropathic pain: “The pain begins dropping in minutes and declines in a time-dependent fashion over 30 minutes, requiring a maximum of 60 minutes to reach optimal benefit. Treatment beyond 60 minutes did not produce any additional improvement.” After pain is reduced, McMakin addresses range of motion: “Trial and error showed that if the patient was treated with the frequencies 13Hz on one channel and 396 Hz on the second channel while moving the limb (and nerve) to edge of the range, within the limits of comfort, the range of motion would return to normal within 10 to 15 minutes.”

Quantum Neurology®, developed by George Gonzalez, DC, who sought a way to treat his wife’s spinal cord injury, is the third technique. This patented system for evaluation and correction of neurological weakness uses neurological activation, physical mobilization, and light therapy with an LED device. Quantum Neurology is not viewed as a treatment to cure specific conditions. Rather, the company website states, “The goal with Quantum Neurology® Rehabilitation is to exercise and strengthen the patient’s Nervous System….the more efficient the Nervous System, the more able the body can handle the stress of processing and healing.”

All three techniques are non-invasive, non-pharmaceutical approaches for helping the nervous system regain balance and heal.

Kent C. Heart Rate Variability to Assess the Changes in Autonomic Nervous System Function Associated with Vertebral Subluxation.

McMakin C. Nonpharmacologic Treatment of Neuropathic Pain Using Frequency Specific Microcurrent. The Pain Practitioner. Fall 2010.

Quantum Neurology® Frequently Asked Questions and Answers. https://quantumneurology.com

van der Merwe K. Putting Out the Fire: A Brand New Approach to Treating RSD/CRPS. April 12, 2016. https://rsds.org/new-approach-rsd-crps/.

Chronic Fatigue, Fibromyalgia, and Idiopathic Intracranial Hypertension

Idiopathic intracranial hypertension (IIH) may be an underlying cause of chronic fatigue syndrome and fibromyalgia in some patients, according to two recent articles in Medical Hypotheses. In the first article, J. Nicholas P. Higgins and British colleagues hypothesize that chronic fatigue syndrome could be “the most common and least severe” sign of idiopathic intracranial hypertension. Fatigue and headache are primary symptoms for both conditions. Other frequent symptoms that the two conditions share are poor memory, inability to concentrate, low mood, dizziness, muscle and joint pains. Papilloedema, swelling of the optic disc, is the distinguishing sign of IIH; but not all patients with intracranial hypertension develop papilloedema: “…these patients may be clinically indistinguishable from patients with chronic fatigue syndrome,” say the authors.

Higgins et al tested for IIH in 20 patients diagnosed with chronic fatigue syndrome and who also suffered with headaches, using lumbar puncture. Ten percent had “unequivocal IIH according to current criteria.” The mean craniospinal fluid pressure for the group was high normal (19 cm H2O). “More importantly, we found that, regardless of whether the opening pressure matched IIH criteria, when intracranial pressure was reduced by drainage of CSF, 85% of patients reported an amelioration of symptoms, including fatigue,” they wrote. The authors warn that their hypothesis needs controlled clinical trials to determine if IIH truly underlies chronic fatigue syndrome in some patients, particularly those who suffer with headaches.

A Belgium team, led of M. Hulens, reports that radicular pain (stemming from nerve roots) is a “common but under-recognized symptom” in people with idiopathic intracranial hypertension. Neuralgic pain is also a defining characteristic of fibromyalgia. People diagnosed with fibromyalgia also experience many of the symptoms found in chronic fatigue syndrome, listed above, such as brain fog and memory problems. Hulens et al theorize that the widespread pain experienced by people diagnosed with fibromyalgia is due to compression of the nerve root fibers, caused by chronic postural idiopathic cerebrospinal hypertension.

Removing cerebrospinal fluid to alleviate symptoms is invasive. Perhaps, the upper cervical chiropractic treatment described by David I. Minkoff, MD, and Julie Mayer Hunt, DC, in their October 2018 Townsend Letter article would be an alternative first option. Dr. Minkoff reports that patients suffering from headaches, dizziness, brain fog, memory loss, POTS, and symptoms of autonomic dysfunction have benefited from this treatment.

Higgins JNP, et al. Chronic fatigue syndrome and idiopathic intracranial hypertension: Different manifestations of the same disorder of intracranial pressure? Medical Hypotheses. 2017;105:6-9.

Hulens M, et al. Fibromyalgia and unexplained widespread pain: The idiopathic cerebrospinal pressure dysregulation hypothesis. Medical Hypotheses. 2018;110:150-154.

Minkoff DI, Hunt JM. A Mystery Answer to Restoring Brain Health. Townsend Letter. October 2018.

Electrohypersensitivity and Brain Abnormalities

Gunnar Heuser and Sylvia A. Heuser have observed that people with electrohypersensitivity and those with chemical sensitivity experience similar symptoms, including headaches, cognitive and memory problems, intermittent problems with balance, weakness, and intermittent tremor. Twenty years ago, Dr. Heuser co-authored studies showing consistent abnormalities in brain function (increased activity in the amygdala) among people with multiple chemical sensitivity, using SPECT and PET scans. With the increasing number of patients who are reporting marked reactions to electromagnetic fields (EMFs), he sought to find objective evidence of dysfunction.

For their investigation, ten adult patients with electromagnetic hypersensitivity agreed to have functional magnetic resonance imaging (fMRI) brain scans. They refused PET and SPECT scanning because of the radioactivity involved. Functional MRI shows which tissues are getting more blood flow, indicating increased activity. All 10 reported symptoms that arose with EMF exposure and usually decreased or resolved when they removed themselves from the EMF source. EMFs are emitted by cell phones, cell phone towers, smart meters, power lines, wi-fi, medical equipment, and other devices.

The patients’ standard laboratory tests were within normal limits. Other conditions known to cause multi-system complaints, such as thyroid problems, diabetes, and autoimmune disease, were ruled out after careful evaluation. Five of the 10 had a history of head injury, and all but one had a history of chemical exposure.

Although regular MRIs indicated nothing remarkable in these patients, the fMRI brain scans for the 10 patients showed similar abnormalities. Specifically, all showed hyperconnectivity of the anterior component of the default mode in the medial orbitofrontal area. This type of abnormality is also seen in traumatic brain injury, chronic pain, substance abuse, and/or OCD.

This is the first study to look at functional connectivity after exposure to EMF. The authors suggest that fMRIs could be used as a diagnostic aid for evaluating patients who report electrohypersensitivity. They realize that their observations here need to be duplicated by other researchers who can conduct larger studies—which requires funding. No foundation or financial entity provided money for this investigation. The participants paid for their own consultations and testing, except for partial payment from a charity for two patients. Insurance companies did not reimburse these patients for the costs.

Given our ever-expanding exposure to EMFs, the problem of electrohypersensitivity is likely to increase. Documenting consistent changes in brain function among affected people would verify that their symptoms are not a figment of their imaginations.

Heuser G, Heuser SA. Functional brain MRI in patients complaining of electrohypersensitivity after long term exposure to electromagnetic fields.. Rev Environ Health. 2017;32(3):291-299.