Therapeutic Potential of Alternating Magnetic Fields for Normalizing Blood Parameters and Restoring Renal, and Cardiac Function in Diabetic Mice

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DOI: 10.18502/ajmb.v18i2.21504

• Tirono, Mokhamad Department of Physics, Faculty of Science and Technology, State Islamic University of Maulana Malik Ibrahim of Malang, Malang City, East Java, Indonesia, Tel: +62 341 551 354, 812 1633 1678; E-mail: mokhtirono@uin-malang.ac.id
  

• Samsu Hananto, Farid
  - Department of Physics, Faculty of Science and Technology, State Islamic University of Maulana Malik Ibrahim of Malang, Malang City, East Java, Indonesia

Attention to the health conditions of the elderly population is increasing due to their heightened vulnerability to diseases. Age is an important factor in understanding health, as the body’s immune resistance tends to decline with advancing age ¹. The aging process is typically associated with a decline in organ function, resulting in decreased productivity and greater vulnerability to disease ². Diabetes Mellitus (DM) is commonly found in elderly individuals. Globally, the estimated prevalence of diabetes in adults aged 20-79 years has more than tripled since 2000, rising from approximately 151 million (4.6%) to 537 million (10.5%) in 2021 ³ . Diabetes is characterized by chronic hyperglycemia and abnormalities in carbohydrate metabolism ⁴.  DM can make sufferers prone to complications, which may ultimately result in impaired kidney function ⁵. DM causes blood glucose levels to increase, leading to increased blood viscosity and a higher risk of hyperlipidemia, hypertriglyceri-demia, and abnormal platelet formation. Further risks include increased cholesterol levels, triglycerides, and atherosclerosis, which can ultimately lead to coronary heart disease ⁶.

Currently, the treatment of diabetes typically involves the long-term use of chemical and herbal medications. However, prolonged use of chemical drugs may cause side effects that can be harmful to health, particularly in individuals with diabetes ⁷. The current principle of diabetes treatment is to maintain blood glucose levels within normal limits, as there is no medication that can completely cure the disease. The use of herbal medicines still requires careful consideration of their toxicity, efficacy, and standardization ⁸. Another common way to maintain glucose levels is to avoid foods that contain a lot of glucose. Meanwhile, foods that contain a lot of glucose contain other nutrients needed by the body, so they have the potential to disrupt the health of other organs. Therefore, other efforts to treat diabetes by minimizing side effects need to be undertaken.

In recent years, extensive research has explored the application of magnetic fields to address various health problems. Bahaoddini et al ⁹ reported that exposing mice to a magnetic field with a frequency of 50 Hz, and a magnetic flux density of 500 μT for 10 hr per day over 2 months significantly reduced blood cholesterol levels. Similarly, another study reported that mice exposed to the same magnetic field parameters had lower cholesterol levels compared to controls¹⁰. Takeuchi and Iwasaka ¹¹ demonstrated that applying a magnetic field to Monosodium Urate (MSU) crystals can increase the rate of crystal dissolution. Pulsed magnetic field treatment of 1.3 T for 1 min has been shown to reduce blood viscosity by 20-30%, while Lotfi et al ¹² reported that static or 50 Hz pulse magnetic fields decreased blood glucose concentrations in BALB/C mice. Tao and Huang ¹³ also confirmed that a 1.3 T magnetic field in blood flow can lower blood viscosity by 20-30% within one min.

Several previous studies have shown that magnetic fields may positively affect the circulatory system and blood composition. These studies generally use magnetic fields with a high flux density of around 1.3 T or involve prolonged exposure times of up to 10 hr/day. Theoretically, the strength of the interaction force generated by a magnetic field depends on the field gradient ¹⁴. Therefore, this study uses an alternating magnetic field so that the required magnetic flux density is lower and the treatment time is shorter. This study aims to find the optimum effect of magnetic field exposure on glucose levels, hemoglobin, erythrocytes, cholesterol, and blood viscosity of mice, and its effects on kidney, blood and heart histology.

Attention to the health conditions of the elderly population is increasing due to their heightened vulnerability to diseases. Age is an important factor in understanding health, as the body’s immune resistance tends to decline with advancing age ¹. The aging process is typically associated with a decline in organ function, resulting in decreased productivity and greater vulnerability to disease ². Diabetes Mellitus (DM) is commonly found in elderly individuals. Globally, the estimated prevalence of diabetes in adults aged 20-79 years has more than tripled since 2000, rising from approximately 151 million (4.6%) to 537 million (10.5%) in 2021 ³ . Diabetes is characterized by chronic hyperglycemia and abnormalities in carbohydrate metabolism ⁴.  DM can make sufferers prone to complications, which may ultimately result in impaired kidney function ⁵. DM causes blood glucose levels to increase, leading to increased blood viscosity and a higher risk of hyperlipidemia, hypertriglyceri-demia, and abnormal platelet formation. Further risks include increased cholesterol levels, triglycerides, and atherosclerosis, which can ultimately lead to coronary heart disease ⁶.

Currently, the treatment of diabetes typically involves the long-term use of chemical and herbal medications. However, prolonged use of chemical drugs may cause side effects that can be harmful to health, particularly in individuals with diabetes ⁷. The current principle of diabetes treatment is to maintain blood glucose levels within normal limits, as there is no medication that can completely cure the disease. The use of herbal medicines still requires careful consideration of their toxicity, efficacy, and standardization ⁸. Another common way to maintain glucose levels is to avoid foods that contain a lot of glucose. Meanwhile, foods that contain a lot of glucose contain other nutrients needed by the body, so they have the potential to disrupt the health of other organs. Therefore, other efforts to treat diabetes by minimizing side effects need to be undertaken.

In recent years, extensive research has explored the application of magnetic fields to address various health problems. Bahaoddini et al ⁹ reported that exposing mice to a magnetic field with a frequency of 50 Hz, and a magnetic flux density of 500 μT for 10 hr per day over 2 months significantly reduced blood cholesterol levels. Similarly, another study reported that mice exposed to the same magnetic field parameters had lower cholesterol levels compared to controls¹⁰. Takeuchi and Iwasaka ¹¹ demonstrated that applying a magnetic field to Monosodium Urate (MSU) crystals can increase the rate of crystal dissolution. Pulsed magnetic field treatment of 1.3 T for 1 min has been shown to reduce blood viscosity by 20-30%, while Lotfi et al ¹² reported that static or 50 Hz pulse magnetic fields decreased blood glucose concentrations in BALB/C mice. Tao and Huang ¹³ also confirmed that a 1.3 T magnetic field in blood flow can lower blood viscosity by 20-30% within one min.

Several previous studies have shown that magnetic fields may positively affect the circulatory system and blood composition. These studies generally use magnetic fields with a high flux density of around 1.3 T or involve prolonged exposure times of up to 10 hr/day. Theoretically, the strength of the interaction force generated by a magnetic field depends on the field gradient ¹⁴. Therefore, this study uses an alternating magnetic field so that the required magnetic flux density is lower and the treatment time is shorter. This study aims to find the optimum effect of magnetic field exposure on glucose levels, hemoglobin, erythrocytes, cholesterol, and blood viscosity of mice, and its effects on kidney, blood and heart histology.

Cholesterol levels: Exposure to alternating magnetic fields in mice can reduce blood cholesterol levels. The magnitude of the decrease in cholesterol levels is influenced by the magnetic flux density and its frequency. Cholesterol levels without exposure were 111.67±2.08 mg/dL, while when exposed to a magnetic field with a magnetic flux density of 0.3 mT and a frequency of 200 Hz for 20 min a day, after 5 days it became 100.67±1.16 mg/dL. Meanwhile, when mice were exposed to a magnetic flux density of 0.6 mT and a frequency of 200 Hz, their cholesterol levels dropped to 101.67±1.53 mg/dL, as seen in figure 2. The results of the test using statistics showed that changes in frequency and magnetic flux density had a significant effect (p=0.002, £0.05) on cholesterol levels. The lowest cholesterol levels were obtained from exposure using a magnetic flux density of 0.3 mT with a frequency of 200 Hz.

Glucose levels: Glucose is one of the most important carbon sources used as an energy source. Normal fasting blood glucose levels in adults are 70-100 mg/dL. Blood glucose levels were measured after the mice were fasted for 8 hr. Exposure to magnetic fields affected blood glucose levels in mice. Changes in frequency and magnetic flux density of the magnetic field used had a significant effect (p=0.000, ≤0.05) on glucose levels, as shown in figure 3. Without exposure to magnetic fields, blood glucose levels were 600.00±0.00 mg/dL. Exposure to magnetic fields with a magnetic flux density of 0.3 mT and frequencies of 50, 100, 150, and 200 Hz caused blood glucose levels to be 229.00±5.29; 153.00±4.00; 113.33±6.43; and 583.33± 9.23 mg/dL, respectively. Meanwhile, exposure with a magnetic flux density of 0.6 mT resulted in 57.67± 3.51; 47.33±5.69; 344.33±9.61; and 533.67±6.66 mg/dL, respectively.

Blood viscosity: Viscosity (η) is the internal friction force between molecules and particles that make up a fluid in cylindrical blood vessels. The main determinants of blood viscosity are hematocrit, red blood cell aggregation, and plasma viscosity. Exposure to magnetic fields affects blood viscosity (Figure 4). Blood viscosity without exposure to magnetic fields was 17.86±0.50 mPas. Exposure to magnetic fields with a magnetic flux density of 0.3 mT at frequencies of 50, 100, 150, and 200 Hz for 20 min per day changed blood viscosity to 11.87±0.49; 10.25 0.63; 9.02±0.58 and 17.29±1.09 mPas, respectively. When exposed to a magnetic field with a magnetic flux density of 0.6 mT, viscosity changed successively to 7.47±0.44; 5.15±0.78; 14.30±0.63; and 16.54±0.96 mPas. Statistical tests showed that changes in magnetic field frequency and flux density (p=0.001, £0.05) significantly affected blood viscosity.

Hemoglobin levels: Hemoglobin is a protein in red blood cells that plays an important role in transporting oxygen throughout the body. Exposure to magnetic fields with magnetic flux densities of 0.3 mT and 0.6 mT and magnetic field frequencies of 50-200 Hz has a significant effect (p=0.046, £0.05) on hemoglobin levels, as shown in Figure 5. Exposure to frequencies of 50, 100, 150, and 200 Hz at a magnetic flux density of 0.3 mT changed hemoglobin levels from 13.37±0.21 g/dL to 15.63±.32; 19.63±0.87; 17.73±0.64; and 15.90±0.78 g/dL, respectively. Meanwhile, exposure at a magnetic flux density of 0.6 mTchanged hemoglobin levels to 14.27±0.45; 17.10±0.61; 18.50±0.72; 16.60±0.92 g/dL, respectively. The highest hemoglobin level was observed in the blood of mice exposed to a magnetic flux density of 0.3 mT at a frequency of 100 Hz, namely 19.63±0.87 g/dL.

Number of erythrocytes: Erythrocytes are blood cells that do not have a nucleus, round or slightly oval looking like biconcave discs with a size of 7-8 μm. The normal value of the number of erythrocytes depends on age and gender. Males have 4.4-5.6 million cells/mm³, women 3.8-5.0 million cells/mm³ and children 3.5-5.5 million cells/mm³. The number of erythrocytes in the blood of mice that were not exposed to a magnetic field was 1.46±0.08 million cells/mm³. In mice exposed to a 0.3 mT magnetic field for 20 min a day with a magnetic field frequency of 50, 100,150, and 200 Hz, it changed to 2.57±0.13; 3.85±0.27; 4.67±0.17; 2.20±0.15 million cells/mm³ (Figure 6). Meanwhile, mice exposed to a magnetic flux density of 0.6 mT changed to 2.97±0.40; 4.51±0.23; 6.14±0.52; 1.75±0.07 million cells/mm³. The results of statistical tests showed that changes in frequency and magnetic flux density were significant (p=0.000, £0.05) in changing the number of blood erythrocytes. The number of normal erythrocyte cells was obtained from exposure to a magnetic flux density of 150 Hz at a magnetic flux density of 0.3 mT and 100 Hz at a magnetic flux density of 0.6 mT.

Renal glamorous diameter: The glomerulus is a kidney structure that functions to filter waste and toxins from the blood, as well as remove excess fluid from the body. The diameter of the glomerulus changes due to exposure to magnetic fields (Figure 7). Exposure to magnetic fields with a magnetic flux density of 0.3 mT at frequencies of 50 Hz and 100 Hz, and a magnetic flux density of 0.6 mT at a frequency of 50 Hz, enlarged the glomerular diameter from 55.53±18.95 µm to 65.13±9.89, 61.27± 2.73 µm, and 62.67±8.74 µm, respectively. Meanwhile, the lowest diameter was obtained from exposure to a magnetic field with a magnetic flux density of 0.3 mT at a frequency of 50 Hz, namely 41.47±16.64 µm. However, the results of the statistical test showed that the differences were not significant. The largest change in glomerular diameter occurred at exposure to a magnetic flux density of 0.3 mT and a frequency of 50 Hz (Figure 8).

Histology of erythrocytes: The condition of erythrocytes varied with each exposure, particularly regarding coagulation and the presence of other elements, as shown in figure 9. The most optimal condition, characterized by the lowest cell coagulation and minimal presence of other elements, was observed at exposure to a frequency of 200 Hz and a magnetic flux density of 0.3 mT. In contrast, the highest cell coagulation and greatest presence of other elements occurred at exposure to a frequency of 50 Hz and a magnetic density of 0.6 mT.

Exposure of blood to alternating magnetic fields causes eddy currents and induction of electromotive force ³⁰. The presence of eddy currents can produce a thermal effect. However, in this study the thermal effect did not significantly affect the blood, as temperature measurements of mice after exposure showed no significant increase. Similarly, the induced voltage did not affect the blood. This is evidenced by the observation that exposure at a magnetic flux density of 0.6 mT resulted in a smaller decrease in cholesterol levels compared to exposure at 0.3 mT.

Another possible effect is that cells exposed to a very weak magnetic field experience ion movement across the membrane, particularly calcium ions ³¹. This effect has also been observed in the development of chicken embryos ³². Whole-body exposure of mice in this study highlighted the role of magnetic flux density and frequency in influencing cholesterol, hemoglobin, glucose, blood viscosity, erythrocyte count, and the histology of kidney and erythrocytes.

The liver, as the primary source of lipoproteins and cholesterol in the bloodstream, is a central target in studies such as those conducted by Wang et al ³³. Exposure to alternating magnetic fields with flux densities of 0.3-0.6 mT has been shown to modulate hepatic cholesterol synthesis, thereby influencing circulating cholesterol levels. Interestingly, these metabolic effects occur only at specific frequencies and flux densities ³⁴, suggesting the possibility of resonance-like interactions between magnetic fields and biological systems—a phenomenon that warrants further investigation ²¹.

One proposed mechanism is Ion Cyclotron Resonance (ICR), described by the equation f= qB/2πm. At a magnetic flux density of 0.3 mT and frequencies between 50 and 100 Hz, calcium ions (Ca²⁺) may reach resonance due to their effective mass in biological environments ²¹. Such resonance may facilitate efficient energy transfer, increasing the kinetic energy of ions and enabling them to overcome cellular energy barriers. The resulting elevation in intracellular calcium can function as a secondary messenger that initiates extensive signaling cascades. This pathway may explain observed alterations in glucose metabolism through enhanced insulin sensitivity and modulation of hepatic enzymes, as well as changes in cholesterol synthesis via regulation of HMG-CoA reductase ³⁵.

A complementary explanation involves the Radical Pair Mechanism (RPM). Alternating magnetic fields in the 50-100 Hz range can influence electron spin precession within radical pairs, shifting the balance of singlet–triplet interconversion ³⁶. These spin-dependent changes can elevate the production of Reactive Oxygen Species (ROS), which act as redox signals that activate transcription factors such as Nrf2 and NF-κB. These pathways subsequently modify gene expression and enzymatic activity, including that of HMG-CoA reductase, ultimately altering hepatic cholesterol production and its plasma concentration ³⁷.

Living systems constantly produce free radicals as a result of biochemical reactions in oxidative metabolic processes ³⁸. Exposure to magnetic fields can eliminate the degeneracy of the triplet radical pair energy levels and affect the rate of the these reactions ³⁹. The relatively small energy exchange between the external magnetic field and free radical-driven reactions can induce physiological changes. The decrease in cholesterol levels in the blood of mice indicates that the magnetic field affects the hormonal system, which can reduce metabolism. When the frequency of the magnetic field applied to diabetic mice is right, it will slow down the metabolism. This causes homeostatic changes and increases insulin release, which can lower blood glucose levels. The liver plays an important role in overall metabolism, particularly in patients with diabetes mellitus ⁴⁰. Therefore, the decrease in blood glucose levels in this study was not linear with changes in the frequency of the magnetic field applied.

The aggregate chains parallel to the direction of blood flow help maintain stable blood viscosity, which then slowly increases again to restore its original value ⁴¹. Exposure to magnetic fields causes these chains to align and reduces blood viscosity ⁴¹. When the applied magnetic field reaches zero, the effective viscosity equals the kinematic viscosity, and the magnetic torque exerted on the blood cells increases friction between the plasma and the red blood cells. Exposure to alternating magnetic fields with low magnetic flux density and aggregate alignment with the direction of blood flow is not the only cause of decreased blood viscosity. In this study, a linear relationship was found between viscosity and blood glucose levels. Therefore, the decrease in viscosity observed is more dominantly caused by a decrease in blood glucose levels.

The alternating magnetic field has a direct effect on the conformation of Hb through its interaction with water molecules bound to Hb ³⁷. Water plays an important role in maintaining protein macromolecules in their natural state ⁴². Exposure to an alternating magnetic field altersthe length of the hydrogen bonds in water, which leads to a more stable structure and results in reduced absorption of the hemoglobin band. This may reflect changes in aggregation state and the local environment, causing conformational changes in the Hb protein. The results of this study indicate that hemoglobin changes are influenced more by frequency than by magnetic flux density.

Mice exposed to alternating magnetic fields experienced changes in the number of erythrocytes. Figure 6 shows an increasing trend at a frequency of 150 Hz and a decreasing trend at 200 Hz. These findings indicate that exposure to magnetic fields can induce oxidative stress in red blood cells. Changes in hemoglobin conformation caused by magnetic fields may lead to a hypoxia-like state, which can stimulate erythrocyte production in the bone marrow ⁴³.

Free radicals, especially ROS, are products of biochemical reactions in metabolically active cells. Exposure to a sinusoidal alternating magnetic field in the heart induces a window effect on cardiac cells ⁴⁴, as indicated by changes in cell density. Exposure to magnetic fields at a frequency of 50 Hz tends to decrease cell density, whereas at 150 Hz and 200 Hz, cell density increases, as shown in figure 10.

Limitations: This study has several methodological limitations in the characterization of the magnetic field. Numerical simulations using the Finite Element Method (FEM) and three-dimensional magnetic field mapping were not performed. The magnetic field distribution within the exposure chamber was assumed to be homogeneous based on theoretical solenoid calculations, without experimental validation through detailed spatial measurements. The coil’s efficiency in generating a uniform field-including the effects of resistance and inductance-was also not comprehensively modeled.

In terms of dosimetry, the magnetic exposure dose (B=0.3 mT or 0.6 mT) received by each subject was based solely on the nominal magnetic field calculated at the solenoid center. This study did not quantify the influence of edge effects, including field spreading and decay at the coil ends, on subjects located in those regions. Additionally, variations in animal positioning during exposure-such as movement away from the center or closer to the coil walls-were not considered in the dosimetric calculations.

Exposure to low-flux, low-frequency alternating magnetic fields has potential for diabetes therapy. Such exposure may promote cell recovery or cause damage in blood cells, kidneys and heart. However, the optimum conditions of cholesterol levels, glucose, hemoglobin, viscosity, number of erythrocytes, erythrocyte conditions, kidney and heart cells do not always occur at the same frequency and flux density. Therefore, further research is still highly needed.

Ethical consideration: The use of mice as experimental subjects was approved by the Ethics Commission of the Faculty of Science and Technology, State Islamic University of Maulana Malik Ibrahim Malang (No. 04/EC/KEP-FST/2024), with approval granted on May 4, 2024.

We would like to express our gratitude to the Directorate of Islamic Higher Education, Ministry of Religious Affairs of the Republic of Indonesia, and to the State Islamic University of Maulana Malik Ibrahim, Malang.

The authors declare no conflict of interest.