Jan Aaseth

Jan Olav Aaseth (born 20 October 1943) is a Norwegian physician, doctor of philosophy, professor, research advisor in internal medicine, endocrinology, toxicology, and medical biochemistry,[1] and advisor for international scientific journals.[2]

Jan Aaseth
Born (1943-10-20) 20 October 1943
Norway
NationalityNorwegian
OccupationResearch adviser and professor at Innlandet Hospital & Inland Norway University of Applied Medicine, Norway,

Early career and biography

Dr. Aaseth was a university fellow when he in 1976 defended his doctoral thesis at the University of Oslo on mercury toxicity and detoxification. He worked at Oslo University Hospital and became an approved specialist in medical biochemistry in 1979, and later also approved in internal medicine and endocrinology. He was also an EUROTOX-registered toxicologist and approved specialist in occupational medicine. He was appointed professor and head of the Department of Occupational Medicine at University of Tromsø. Later he has been head of the units of Medical Biochemistry and Endocrinology at Innlandet Hospital, combined with an appointment as professor at Inland Norway University of Applied Sciences.[3]

In close collaboration with colleagues in the Nordic countries, Jan Aaseth founded the Nordic Trace Element Society (NTES) in 1985. He has been a guest editor for special issues of several international scientific journals.[2] In 1984 he became a member of the steering group of the Committee for Geomedicine of the Norwegian Academy of Science and Letters.[2] Dr. Aaseth has been president for the Norwegian Association for the Study of Obesity. Dr. Aaseth has published more than 200 scientific papers.[4]

Research on toxic and essential metals

Mercury and other toxic minerals

Aaseth published a toxicological risk analysis of occupational diseases related to inorganic mercury, especially metallic mercury vapor. Available data showed that dental work involving mercury might be an occupational hazard with respect to the nervous system and reproductive processes. Newer evidence indicates that mercury exposure from dental amalgam may cause or contribute to many chronic neurological symptoms and illnesses.[5] Aaseth has acted as a medical expert for the Supreme Court of Norway in questions regarding occupational disease related to mercury exposure in dentistry. Aaseth has participated in medical studies on lead (Pb),[6] cadmium (Cd),[7] arsenic (As),[8] and uranium (U).[9]

Essential trace elements

Aaseth has studied the metabolism of copper[10] and zinc,[11] and the role of the tripeptide glutathione in the trafficking and excretion of essential trace elements.[12]

In series of experiments, Aaseth has studied the protective effect of selenium compounds toward the toxicity of mercury.[13] Antioxidative metalloenzymes appear to have protective functions. Examples on antioxidative metalloenzymes are the superoxide dismutases, SOD1 and SOD2, which have copper, zinc, or manganese, respectively, in their active sites.

Iron deposition in the heart which is seen in transfusional sideroses, e.g., during treatment of thalassemia can precipitate cardiomyopathy. Protective measures include the therapeutic use of new iron chelating agents, which have been studied by Aaseth and co-workers.[14] Furthermore, iron mobilization from brain appears to delay the progression of some neurodegenerative diseases, in particular Parkinson's disease.[15]

Neurology and psychiatry research

In early studies, Aaseth described an increasing trend in the use of drugs and narcotics among Norwegian teenagers,[16] and recently the same trend in other countries.[17]

Aaseth is currently involved in research on the pathogenesis and pathophysiology of degenerative neurological diseases, including Parkinson's disease, Alzheimer's disease, multiple sclerosis, and autism spectrum disorder (ASD). Environmental factors seem to promote deposition of iron in the vulnerable brain foci, and Aaseth has studied and discussed the role of iron chelation in the disease-modifying treatment of Parkinson's disease.[18]

Selenium compounds together with copper chelators appear to play a role in delaying the progression of Alzheimer's disease, presumably by their abilities to inhibit peroxidations and deterioration of the cytoskeleton.[19]

While imaging techniques have disclosed temporal hypoperfusion in individuals who have Alzheimer's disease, larger cerebral regions with hypoperfusion have been found in ASD patients.[20] Evidence suggests that brain inflammation may explain a part of this hypoperfusion. Neuroinflammation in ASD may be precipitated or aggravated by environmental pollutants, such as lead, mercurials and some pesticides including polychlorinated biphenyls (PCBs) and organophosphates.[21]

Mercury is a neurotoxicant and a potential environmental trigger for neuroinflammation with ASD aggravation. Mercury accumulation in the brain is relevant for children with ASD. Based on studies together with Russian researchers, Jan Aaseth has hypothesized that there is a possible relationship between mercury and cadmium exposure, maternal obesity, and ASD.[22]

Research on Endocrine Diseases and Obesity

Dr. Aaseth has also been involved in endocrinological studies, on dysfunctions of the thyroid and parathyroid glands.[23] In particular, he has studied endocrine dysfunctions in obesity,[24] and the impacts of bariatric surgery on the endocrine system.[25]

Cardiology research

In a series of papers, dr. Aaseth has disclosed a role of selenium deficiency in the development of cardiovascular morbidity and mortality.[26] Oxidative stress accompanied by a low-grade inflammatory response appears to aggravate cardiovascular morbidity.[27]

Rheumatology research

Rheumatic disease is an umbrella term for conditions causing chronic pain affecting the joints and/or connective tissue. Common rheumatic diseases include rheumatoid arthritis, Sjögren's syndrome, systemic lupus erythematosus, and also fibromyalgia. Rheumatic diseases are usually accompanied by an inflammatory response apparently triggered by metal delayed-type hypersensitivity (type IV allergy). Dr. Aaseth has studies the effects of disease-modifying agents including anti-TNF-alpha drugs[28] and also selenium compounds.[29] Some of these agents appear to protect against cardiovascular complication.

Toxic metal detoxification

Jan Aaseth has since the 1970s been interested in the physical and chemical properties of mercury and its antidotes, and he has also published several studies and reviews on detoxification of mercury and other heavy metals by use of chelators.[30] In 2016 he was co-editor of a book: "Chelation Therapy in the Treatment of Metal Intoxication."[31]

Chelators remove toxic amounts of metals (lead, iron, etc.) from vital constituents in the organism. The most commonly used metal chelators in clinical toxicology include meso-2,3-dimercapto-succinic acid (DMSA, succimer), sodium 2,3-dimercapto-1-propanesulfonate (DMPS, Unithiol) and calcium-ethylenediamine tetraacetate (CaEDTA). Pathological deposits of iron which occurs, e.g., in thalassemia can be treated by oral iron chelators, deferiprone (Ferriprox) and deferasirox (Exjade) which can be administered in combination.[31]

Both DMPS and DMSA increase the urinary excretion of copper and zinc, which in some patients may give deficiency symptoms. Based on experimental studies and clinical experience Aaseth recommend DMSA to be used against mercury and lead intoxications,[32][33] although recent studies indicate that chelator combinations may facilitate mobilization from the brain.[34]

Selenium and mercury

The essential trace element selenium (Se) appears to be an antidote to mercury (Hg). Se-containing molecules are targets for Hg binding that may at least partially mediate the biological outcome of Hg-Se interaction. Molecular interaction between these elements also involves mutual interaction between Hg and various selenoproteins. Experimental data demonstrate that Se treatment modifies brain Hg retention, modulates neurotoxicity and oxidative stress in the nervous tissue of animals. Human data also indicate that molecular interaction between Hg and Se may have a significant influence on neurodevelopment and neurodegeneration. The hypothesized effectiveness of Se protection against Hg neurotoxicity may be determined by the dose of elements as well as by their particular chemical forms.[13]

References
  1. Eriksen FY. Lege blir samarbeidsprofessor. Glåmdalen 29. april 2013. https://www.glomdalen.no/nyheter/lege-blir-samarbeidsprofessor/s/1-57-6631002.
  2. Tendø Jacobsen T. Vi lever i en farligere verden. SI magasinet 2014; nr. 3: 10-11.
  3. Tendø Jacobsen T. Sterkt fokus på miljøgifter. SI magasinet 2014; nr. 3: 8-9.
  4. Helse Sør-Øst RHF. Hva skjer når giftstoffer angriper hjernen og kroppens hormonbalanse? https://www.helse-sorost.no/nyheter/hva-skjer-nar-giftstoffer-angriper-hjernen-og-kroppens-hormonbalanse.
  5. Aaseth J, Hilt B, Bjørklund G (2018). Mercury exposure and health impacts in dental personnel. Environmental research, 164, 65-69.
  6. Cao, Y., Skaug, M. A., Andersen, O., & Aaseth, J. (2015). Chelation therapy in intoxications with mercury, lead and copper. Journal of Trace Elements in Medicine and Biology, 31, 188-192.
  7. Tinkov, A. A., Filippini, T., Ajsuvakova, O. P., Skalnaya, M. G., Aaseth, J., Bjørklund, G., ... & Vinceti, M. (2018). Cadmium and atherosclerosis: A review of toxicological mechanisms and a meta-analysis of epidemiologic studies. Environmental research, 162, 240-260.
  8. Bjørklund, G., Aaseth, J., Chirumbolo, S., Urbina, M. A., & Uddin, R. (2017). Effects of arsenic toxicity beyond epigenetic modifications. Environmental geochemistry and health, 1-11.
  9. Bjørklund, G., Christophersen, O. A., Chirumbolo, S., Selinus, O., & Aaseth, J. (2017). Recent aspects of uranium toxicology in medical geology. Environmental research, 156, 526-533.
  10. Öhrvik H, Aaseth J, Horn N (2017). Orchestration of dynamic copper navigation–new and missing pieces. Metallomics, 9(9), 1204-1229.
  11. Alexander J, Aaseth J (1980). Biliary excretion of copper and zinc in the rat as influenced by diethylmaleate, selenite and diethyldithiocarbamate. Biochemical Pharmacology, 29(15), 2129-2133.
  12. Aaseth J, Alexander J, Norseth T (1982). Uptake of 51Cr‐chromate by human erythrocytes–a role of glutathione. Acta pharmacologica et toxicologica, 50(4), 310-315.
  13. Bjørklund, G., Aaseth, J., Ajsuvakova, O. P., Nikonorov, A. A., Skalny, A. V., Skalnaya, M. G., & Tinkov, A. A. (2017). Molecular interaction between mercury and selenium in neurotoxicity. Coordination Chemistry Reviews, 332, 30-37.
  14. Flaten, T. P., Aaseth, J., Andersen, O., & Kontoghiorghes, G. J. (2012). Iron mobilization using chelation and phlebotomy. Journal of Trace Elements in Medicine and Biology, 26(2-3), 127-130.
  15. Aaseth, J., Dusek, P., & Roos, P. M. (2018). Prevention of progression in Parkinson’s disease. BioMetals, 1-11.
  16. Aaseth, J., Rekdal, B., & Sund, A. (1975). Utbredelsen av stoffbruk hos unge menn i Norge i 1972–1973. Nordisk Psykiatrisk Tidsskrift, 29(4), 271-278.
  17. Alinejad, S., Aaseth, J., Abdollahi, M., Hassanian‐Moghaddam, H., & Mehrpour, O. (2018). Clinical aspects of opium adulterated with lead in Iran: a review. Basic & clinical pharmacology & toxicology, 122(1), 56-64.
  18. Dusek, P., Schneider, S. A., & Aaseth, J. (2016). Iron chelation in the treatment of neurodegenerative diseases. Journal of Trace Elements in Medicine and Biology, 38, 81-92.
  19. Aaseth, J., Alexander, J., Bjørklund, G., Hestad, K., Dusek, P., Roos, P. M., & Alehagen, U. (2016). Treatment strategies in Alzheimer’s disease: a review with focus on selenium supplementation. Biometals, 29(5), 827-839.
  20. Bjørklund, G., Kern, J. K., Urbina, M. A., Saad, K., ElHoufey, A. A., Geier, D. A., ... & Aaseth, J. (2018). Cerebral hypoperfusion in autism spectrum disorder. Acta Neurobiol Exp, 78(21), 9.
  21. Bjørklund, G., Skalny, A. V., Rahman, M. M., Dadar, M., Yassa, H. A., Aaseth, J., ... & Tinkov, A. A. (2018). Toxic metal (loid)-based pollutants and their possible role in autism spectrum disorder. Environmental research, 166, 234-250.
  22. Tinkov AA, Gritsenko VA, Skalnaya MG, Cherkasov SV, Aaseth J, Skalny A V (2018). Gut as a target for cadmium toxicity. Environmental Pollution, 235, 429434.
  23. Aaseth, J., Frey, H., Glattre, E., Norheim, G., Ringstad, J., & Thomassen, Y. (1990). Selenium concentrations in the human thyroid gland. Biological trace element research, 24(2-3), 147-152.
  24. Aaseth, J., & Støa‐Birketvedt, G. (2000). Glutathione in overweight patients with poorly controlled type 2 diabetes. The Journal of Trace Elements in Experimental Medicine: The Official Publication of the International Society for Trace Element Research in Humans, 13(1), 105-111.
  25. Jansen, A., Lyche, J. L., Polder, A., Aaseth, J., & Skaug, M. A. (2017). Increased blood levels of persistent organic pollutants (POP) in obese individuals after weight loss—A review. Journal of Toxicology and Environmental Health, Part B, 20(1), 22-37.
  26. Alehagen, U., Aaseth, J., & Johansson, P. (2015). Reduced cardiovascular mortality 10 years after supplementation with selenium and coenzyme Q10 for four years: follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly citizens. PLOS ONE, 10(12), e0141641.
  27. Alehagen, U., Lindahl, T. L., Aaseth, J., Svensson, E., & Johansson, P. (2015). Levels of sP-selectin and hs-CRP Decrease with Dietary Intervention with selenium and coenzyme Q10 Combined: a secondary analysis of a randomized clinical trial. PLOS ONE, 10(9), e0137680.
  28. Arvidson, N. G., Larsen, A., Aaseth, J., & Larsson, A. (2007). Short‐term effects of the TNFα antagonist infliximab on the acute phase reaction and activities of daily life in patients with rheumatoid arthritis. Scandinavian journal of clinical and laboratory investigation, 67(3), 337-342.
  29. Aaseth, J., Haugen, M., & Førre, Ø. (1998). Rheumatoid arthritis and metal compounds—perspectives on the role of oxygen radical detoxification. Analyst, 123(1), 3-6.
  30. Aaseth J (1983). Recent advance in the therapy of metal poisonings with chelating agents. Human Toxicology, 2(2), 257-272.
  31. Aaseth J, Crisponi G, Anderson O (2016). Chelation therapy in the treatment of metal intoxication. Academic Press.
  32. Aaseth J, Friedheim EA (1978). Treatment of methyl mercury poisoning in mice with 2, 3‐dimercaptosuccinic acid and other complexing thiols. Acta pharmacologica et toxicologica, 42(4), 248-252.
  33. Aaseth, J., Skaug, M. A., Cao, Y., & Andersen, O. (2015). Chelation in metal intoxication—principles and paradigms. Journal of Trace Elements in Medicine and Biology, 31, 260-266.
  34. Aaseth J, Ajsuvakova OP, Skalny V, Skalnaya MG, Tinkov AA (2018). Chelator combination as therapeutic strategy in mercury and lead poisonings. Coordination Chemistry Reviews, 358, 1-12.
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