Re5 Transcranial PEMF

This post reviews trans cranial Re5 PEMF device that uses very low frequency PEMF to treat Parkinson’s Disease. The former acts by increasing EPO in the CSF. The latter increases cognitive and mitochondria performance while decreasing Aβ aggregation.

for Biohackers

wave	low Hz	high Hz	cycle time, min
alpha	10	13	10
beta 1	12.5	16	4
beta 2	16.5	20	4
beta 3	20	28	4
delta	1.5	3	20
theta	5	6	20
mu	8.5	11	20
SMA	13	15	10
gamma	32	47	10

Transcranial PEMF studies on PubMed

A table was compiled based on a PubMed search of “transcranial PEMF.” Most studies involve what appears to be the multi-Purpose Re5. These are some of them.

year	condition	model	magnetic field	frequency	duration	results performance	results biochem	reference	Country
2021	Parkinson’s	human clinical trial	±50 V,	3 ms, 50 ±50 V,	30 min day 26 weeks	🔽 sit to stand time	🔼 erythropoietin in cerebral spinal fluid	[1]	Denmark
2018	Parkinson’s	human case report		3 ms, 50 Hz	30 min day 26 weeks	🔼 hand writing still fine 3 month	normalized emg 🔛	[2]	Denmark
2019	Parkinson’s	clinical trial 50 humans	±50 V,	3 ms, 50 Hz	30 min day 8 weeks	🔽 hand tremor		[3]	Denmark
2018	Parkinsons	clinical trail 97 humans	±50 V,	3 ms, 50 Hz	30 min day 8 weeks	🔼 force chair rise		[4]	Denmark
2014	multiple chemical sensitivity	3 case studies	±50 V, mT	3 ms, 50 Hz	30 min day 8 weeks 5d/wk	🔼 depression, probably not causal	🔽 2 of 3 capsaicin hypersensitivity	[5]	Denmark
2014	Depression	31 1x day, 34 2x day			5 week	🔽 Hamilton score		[6]	Denmark
2015	Depression continued	“	“	“	“	w/out apathy 1x good, w/ 2x day		[7]	Denmark
2020	Depression	58 human clinical trial		55 Hz	5 weeks	🔽 Hamilton symptom score		[8]	Denmark
2019	neuropathic pain	20 human clinical trial, controlled	2-3mT		30min	time dependent change in warmth	no change in pain	[9]	Netherlands
2021	post concussion syndrome	7 case studies	2 mV/cm	50 Hz	30 min day 5 weeks	some headaches	🔽symptoms	[10]	Denmark
2020	post concussion headache	20 clinical trial		10 Hz	10 trains 60 pulses/train 600 pulses Inter-train interval 45s.	🔽 headache		[11]	Canada
2019	post concussion syndrome	18, sham vs PEMF		20 Hz	750 pulses/day)			[12]	Canada
2022	Alzheimer’s	8 subject clinical trial	20 V/m	915 MHz	2 mo 2x/day	rebalancing of 11 of 12 cytokines examined.		[14]	USA
2019	Alzheimer’s	8 subject clinical trial		915 MHz		🔼 cognitive test	🔽 Plasma Aβ1-40 levels oligomers , p-tau	[15]	USA

Use of PEMF to treat concussions has been reviewed better elsewhere. [13] These studies generally do not report the magnetic/electric field intensity.

The molecular basis of the Danish Re5 PEMF device

Most, if not all Danish studies, appear to be with the Re5 NTS Parkinson Treatment System, Re5, (Frederiksberg, Denmark). Transcranial PEMF is well researched by the Danes. A 2021 publication found an increase in erythropoietin n the cerebral spinal fluid of Parkinson’s Disease patients. [1] The model used to explain these results washypoxia inducible factor HIF controlling. PHD, proyl hydroxylase domain proteins have a complicated relationship between EPO, iron and oxygen sensing as reviewed by Ogawa 2023. UniProt’s annotation of PHD2 offers some insight. The Fe binding amino acids in the human isoform are His297, Asp299, and His358. Chowdhury 2011 reported that the catalytic domain of PHD2 to reacts with nitric oxide both at its Fe(II) and nitrosylation of its cysteine residues Cys201, Cys208, Cys302, Cys323, and Cys326. Some of these thiols are close to the active sites. The Jensen 2021 [1] model is a good one. This particular cartoon is not from Jensen but an image search modified for discussion of the Jensen model.

• The authors proposed that the link between T-PEMF, CSF-EPO, and movement speed needed further investigation.
• T-PEMF may modulate cerebral levels of EPO, VEGF, and dopamine. EPO and VEGF by way of a common transcription factor, hypoxia induced factor-1α (HIF-1α),
• At normal oxygen levels, HIF-1α is continuously and rapidly degraded. Not mentioned by Jensen 2021 reactive oxygen species might also modulate degradation of HIF-1α. PEMF might be acting on cry2 and/or the mitochondria complex II.
• Increased endogenous nitric oxide seems to reduce degradation and thus stabilizes the level PEMF can induce nitric oxide mediated cerebral arteriolar dilation, leading to increased microvascular blood flow and tissue oxygenation in healthy rats
• HIF-1α also regulates tyrosine hydroxylase (TH), which is rate-limiting in dopamine synthesis.
• EPO, produced by T-PEMF, may thus improve functional performance by increasing the dopamine level in the brain and protection of dopaminergic neurons. In a cell culture model of Parkinson’s EPO was protective via PI3K/Akt/FoxO3a coupled to the EPO receptorPubMed This site has addressed 30 Hz PEMF on the PI3K/AkteNOS pathway. Could this be the source of NO and HIF-1α?
• The authors observed observed unchanged plasma EPO concentrations despite increased CSF levels. The blood brain barrier may limits the passage of EPO. Plasma concentration of EPO is not biomarker for CSF-EPO.
• The featured image shows tissue distribution of EPO, a protein produced in large amounts in the liver. If EPO appears in the CSF, one would hypothesize that the transcranial PEMF might be increasing the blood brain barrier permeability of this small peptide.

O’ztas, B., Kalkan, T., Tuncel, H. (2004). Influence of 50 Hz frequency sinusoidal magnetic field on the BBB permeability of diabetic rats. Bioelectromagnetics 25:400–402. PubMed

“The combined effects of diabetes and a 50 Hz, 5 mT RMS flux density sinusoidal magnetic field for 8 h a day, for 21 consecutive days on the permeation of Evans-blue dye through the blood-brain barrier were studied in male Wistar albino rats. Our results suggest that magnetic field has no effect on the blood-brain barrier permeability in normoglycemic animals, but that diabetic rats are vulnerable to magnetic fields.”

Parkinson’s and Alzheimer’s mitophagy

Mitophagy is a specialized form of autophagy for the removal of damaged and excess mitochondria that produce cell damaging reactive oxygen species. Parkinson’s Disease defective autophagy is a given. Reddy and Oliver 2021 have a good review on defective mitophagy in Alzheimer’s Disease. One might argue that the Re5 does not target defective mitophagy in Parkinson’s Disease but rather shores up the brain’s oxidative defenses against the oxidative stress associated with defective mitochondria via EPO expression. Yang 2021 have a good review on the role of mitophagy in ASD. The Yang review mentioned Activating molecule in BECN1-regulated autophagy protein 1 (Ambra1). Ambra1 interacts with the ubiquitin ligase Parkin and with lysosome targeting LC3. Could the Re5 mitigate issues of suboptimal Ambra1 in ASD or schizophrenia? This discussion is beyond the scope of this post on transcranial PEMF: VLF and radio/microwave frequency.

⚠️Thoughts for the biohackers

RE5 session video give the biohacker an idea of what the positioning of the coils is all about. The woman in this video has a headband with several coils. It is not the end of the world if they do not stay in perfect place. Re5 feel good animation around 22 seconds seems to show where they might think the magnetic fields are targeting. Image of a woman wearing RE5 coils can be taken as encouragement or a warning to biohackers. If you intend to hack, it might be a good idea to consult with your neurologist as to the best position for your coils. Have them give you tests to tell you if you are doing harm, good, or no change.

References

1. Jensen BR, Malling ASB, Schmidt SI, Meyer M, Morberg BM, Wermuth L. Long-term treatment with transcranial pulsed electromagnetic fields improves movement speed and elevates cerebrospinal erythropoietin in Parkinson’s disease. PLoS One. 2021 Apr 28;16(4):e0248800 PMC free paper
2. Jensen BR, Malling ASB, Morberg BM, Gredal O, Bech P, Wermuth L. Effects of Long-Term Treatment with T-PEMF on Forearm Muscle Activation and Motor Function in Parkinson’s Disease. Case Rep Neurol. 2018 Aug 29;10(2):242-251. PMC free paper
3. Malling ASB, Morberg BM, Wermuth L, Gredal O, Bech P, Jensen BR. The effect of 8 weeks of treatment with transcranial pulsed electromagnetic fields on hand tremor and inter-hand coherence in persons with Parkinson’s disease. J Neuroeng Rehabil. 2019 Jan 31;16(1):19. PMC free paper
4. Malling ASB, Morberg BM, Wermuth L, Gredal O, Bech P, Jensen BR. Effect of transcranial pulsed electromagnetic fields (T-PEMF) on functional rate of force development and movement speed in persons with Parkinson’s disease: A randomized clinical trial. PLoS One. 2018 Sep 25;13(9):e0204478. PMC free article
5. Tran MTD, Skovbjerg S, Arendt-Nielsen L, Bech P, Lunde M, Elberling J. Two of three patients with multiple chemical sensitivity had less symptoms and secondary hyperalgesia after transcranially applied pulsed electromagnetic fields. Scand J Pain. 2014 Apr 1;5(2):104-109. free paper
6. Straasø B, Lauritzen L, Lunde M, Vinberg M, Lindberg L, Larsen ER, Dissing S, Bech P. Dose-remission of pulsating electromagnetic fields as augmentation in therapy-resistant depression: a randomized, double-blind controlled study. Acta Neuropsychiatr. 2014 Oct;26(5):272-9. PubMed
7. Bech P, Lunde M, Lauritzen L, Straasø B, Lindberg L, Vinberg M, Undén M, Hellström LC, Dissing S, Larsen ER. The Diagnostic Apathia Scale predicts a dose-remission relationship of T-PEMF in treatment-resistant depression. Acta Neuropsychiatr. 2015 Feb;27(1):1-7. PubMed
8. Larsen ER, Licht RW, Nielsen RE, Lolk A, Borck B, Sørensen C, Christensen EM, Bizik G, Ravn J, Martiny K, Vinberg M, Jankuviené O, Jørgensen PB, Videbech P, Bech P. Transcranial pulsed electromagnetic fields for treatment-resistant depression: A multicenter 8-week single-arm cohort study. Eur Psychiatry. 2020 Feb 18;63(1):e18.PMC free paper
9. Geraets CNW, van Beilen M, van Dijk M, Kleijer H, Köhne C, van der Hoeven JH, Groen GJ, Ćurčić-Blake B, Schoevers RA, Maurits NM, Kortekaas R. Lack of analgesic effects of transcranial pulsed electromagnetic field stimulation in neuropathic pain patients: A randomized double-blind crossover trial. Neurosci Lett. 2019 Apr 23;699:212-216 free paper
10. Meek BP, Hill S, Modirrousta M. Accelerated repetitive transcranial magnetic stimulation in the treatment of post-concussion symptoms due to mild traumatic brain injury: a pilot study. Brain Inj. 2021 Jan 5;35(1):48-58. PMC free paper
11. Stilling J, Paxman E, Mercier L, Gan LS, Wang M, Amoozegar F, Dukelow SP, Monchi O, Debert C. Treatment of Persistent Post-Traumatic Headache and Post-Concussion Symptoms Using Repetitive Transcranial Magnetic Stimulation: A Pilot, Double-Blind, Randomized Controlled Trial.J Neurotrauma. 2020 Jan 15;37(2):312-323. PMID: Clinical Trial.
12. Moussavi Z, Suleiman A, Rutherford G, Ranjbar Pouya O, Dastgheib Z, Zhang W, Salter J, Wang X, Mansouri B, Lithgow B. A Pilot Randomised Double-Blind Study of the Tolerability and efficacy of repetitive Transcranial Magnetic Stimulation on Persistent Post-Concussion Syndrome.Sci Rep. 2019 Apr 2;9(1):5498. PMID: Free PMC article. Clinical Trial.
13. Mollica A, Safavifar F, Fralick M, Giacobbe P, Lipsman N, Burke MJ. Transcranial Magnetic Stimulation for the Treatment of Concussion: A Systematic Review. Neuromodulation. 2021 Jul;24(5):803-812. doi: 10.1111/ner.13319. Epub 2020 Nov 12. PMID: 33184973 Review. Sci-Hub free paper