Low-energy amplitude-modulated radiofrequency electromagnetic fields as a systemic treatment for cancer: review and proposed mechanisms of action.

Liver cancer is currently the fourth leading cause of cancer-related deaths. Based on the 5-year survival rate, it is the second deadliest form of cancer. This review focuses on medical devices that emit low-power electromagnetic fields (EMFs) with a carrier frequency of 27.12 MHz and an amplitude modulation between 10 Hz and 150 kHz. The study summarizes the available evidence on the efficacy and safety of exposure to low-energy, amplitude-modulated radiofrequency electromagnetic fields (LEAMRFEMF) in patients with liver cancer. The emitted power is too low to cause noticeable tissue heating. Rather, the effects of LEAMRFEMF exposure are based on the resonant interactions of electromagnetic waves with subcellular structures in normal and cancerous human cells. Within cells, charged molecules are distributed across membranes, creating electrical and chemical potential differences similar to those in a battery. These potential differences generate the forces that move ions, which underlie nearly all physiological processes in cells. Cells also contain highly charged macromolecular structures, including microtubules (MTs). In addition to their known role in cell division, microtubules propagate electrical signals within cells.

The study reports on two medical LEAMRFEMF devices operating at 27.12 MHz: P1 (TheraBionic GmbH, Ettlingen, Germany) and AutEMdev (Autem Therapeutics, Hanover, New Hampshire, USA). These devices have a power output of 100 mW, which is about 1,000 times lower than a cell phone and 100,000 times lower than devices used for thermal tumor ablation. The specific absorption rate (SAR) is 1.77 mW/kg. Furthermore, the frequency ranges differ from those used in telecommunications. Both devices use sinusoidal amplitude modulation of the carrier wave. The AutEMdev uses frequencies between 10 Hz and 20 kHz, while the P1 uses frequencies between 0.1 Hz and 150 kHz. The devices' physiological and therapeutic effects may be due to the fixed 27.12 MHz carrier wave and amplitude modulation. The authors hypothesize that electromagnetic waves at these frequencies resonate with the vibrations of charged macromolecular structures and ionic currents within cells, much like a bell resonates when exposed to sound waves of the correct frequency. This means that although the device's antenna is placed in the patient's mouth, the entire human body also becomes an antenna. With the exception of bones, the effects of exposure are distributed throughout the body.

The first reported potential clinical benefit of LEAMRFEMF is its ability to promote sleep in patients with insomnia. The effect of radiofrequency EMF on the human brain’s alpha waves, which oscillate at 8 to 13 Hz, could explain these observations. Two in vitro studies found that growth inhibition of liver cancer cell lines occurred more readily at previously identified liver cancer-specific frequencies than at breast cancer-specific or randomly selected frequencies. Evidence suggests that calcium influx via the voltage-gated CACNA1H calcium channel is involved in the anticancer effects. To date, five reports have been published in which the AutEMdev or P1 device were used in patients with liver cancer. A pooled analysis revealed that the median overall survival (OS) for patients who received the TheraBionic P1 device treatment as first-line therapy was 6.7 months, which is slightly higher than the 4.6-month median OS for historical control patients who received sorafenib chemotherapy. These results led to the initiation of a larger, multicenter clinical trial, which yielded similar results. Studies with the AutEMdev and P1 device provided evidence of antitumor efficacy and/or maintenance or improvement of health-related quality of life in patients who continued treatment. The prospective study cohort had longer overall survival than the control group. Apart from mild fatigue and occasional irritation of the oral mucosa (when combined with standard chemotherapy), the treatment is free of side effects.

Carcinogenesis can be viewed as a phase transition in which normally synchronized, homogeneous, and differentiated cells in ordered tissues become asynchronous, heterogeneous, dedifferentiated, and proliferative cancer cells in disordered tumors. Resting membrane potentials are also altered (significantly reduced), and metabolism shifts from oxidative phosphorylation to glycolysis. Nearly all cells possess a resting membrane potential, and voltage-gated ion channels are present in non-excitable cells as well. (These ion channels are located in cell and mitochondrial membranes. Microtubules form a "cabling" system that extends within the cell and docks onto the membranes or ion channels; editor’s note.) Microtubules conduct electrical currents via surrounding counterions and are more conductive than the cytoplasm. Therefore, they act as a main pathway for ionic wave propagation in the cell. The resonant coupling of electromagnetic fields (EMFs) with microtubules, whereby microtubules act as cellular biological antennas, could form the basis for medical applications of EMFs. Disrupting ionic currents in microtubules could impair cell division and the subcellular mitochondrial trafficking. Microtubules are highly conductive to alternating currents at frequencies near the 27.12 MHz carrier wave of medical LEAMRFEMF devices in the longitudinal direction. The carrier wave likely amplifies ionic currents along microtubules, making cells susceptible to amplitude modulation at lower frequencies. LEAMRFEMF can shift the metabolism of cancer cells away from glycolysis, thus restoring the normal phenotype. The authors calculated the energy dissipated per cell due to EMF-induced ionic currents in microtubules and compared it to total metabolic energy production per cell. They concluded that the energy input from the treatment could significantly contribute to shifting the cellular energy balance from glycolysis toward fatty acid oxidation. Estimates of about 50 fW for the EMF power emitted per cell correspond to about 1.5% of the metabolic power in normal cells. In liver cancer cells, mitochondrial oxidative phosphorylation can be reduced by up to 50%. The human liver normally consumes about 15 W (or 15% of the body’s total metabolic energy). Since glycolysis is nine times less efficient than oxidative phosphorylation, cells must increase their glucose consumption by the same factor to maintain the same energy yield. Consequently, 50 fW per cell can account for up to 13.5% of glucose consumption in glycolytic cells compared to 1.5% in cells undergoing oxidative phosphorylation. The authors demonstrated that the frequency of charge transfer via isolated microtubules in vitro (around 30 Hz) falls within the amplitude modulation frequency range of therapeutic LEAMRFEMF devices. Resonant coupling can generate oscillating ionic currents in the condensed ions surrounding and within the microtubules. These currents can then disrupt ion channels, cell division, motor proteins, mitochondrial trafficking and morphology, and cellular energy balance. These presumed mechanisms of action potentially overlap and are not mutually exclusive. Further investigation of these mechanisms is required. The authors conclude that exposure to LEAMRFEMF is a potential method of altering the behavior of cancer cells in patients with advanced disease.

Editor’s note:

Although many details remain unclear, this is a promising approach. Since this electromagnetic method of fighting or slowing the progression of cancer has virtually no side effects, further research into this biomedical application of EMF would be highly desirable. (AT)