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Hinokitiol has been shown to restore hemoglobin production in rodents. Hinokitiol acts as an iron ionophore to channel iron into cells,[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470741/ [26<nowiki>]</nowiki>][https://www.sciencemag.org/news/2017/05/iron-man-molecule-restores-balance-cells [27<nowiki>]</nowiki>] increasing intracellular iron levels. Approximately 70% of the iron in humans is contained within red blood cells and specifically the hemoglobin protein. Iron is essential to almost all living organisms, and it is a critical element of several anatomical functions such as the oxygen transport system, deoxyribonucleic acid (DNA) synthesis, and electron transport and an iron deficiency can lead to blood disorders such as Anemia which, can be significantly detrimental to both physical and mental performance.[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999603 [28<nowiki>]</nowiki>]
Hinokitiol has been shown to restore hemoglobin production in rodents. Hinokitiol acts as an iron ionophore to channel iron into cells,[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470741/ [26<nowiki>]</nowiki>][https://www.sciencemag.org/news/2017/05/iron-man-molecule-restores-balance-cells [27<nowiki>]</nowiki>] increasing intracellular iron levels. Approximately 70% of the iron in humans is contained within red blood cells and specifically the hemoglobin protein. Iron is essential to almost all living organisms, and it is a critical element of several anatomical functions such as the oxygen transport system, deoxyribonucleic acid (DNA) synthesis, and electron transport and an iron deficiency can lead to blood disorders such as Anemia which, can be significantly detrimental to both physical and mental performance.[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999603 [28<nowiki>]</nowiki>]
'''Zinc synergism'''
Hinokitiol is a Zinc ionophore, and this capability is believed to inhibit viral replication. In brief, as a zinc ionophore, Hinokitiol aids in the transport molecules into cells through a plasma membrane or intracellular membrane, thus increasing the intracellular concentration of the specified molecule (ex. Zinc). Hence, by taking advantage of Zinc’s antiviral properties, in combination with Hinokitiol, Zinc uptake can be accelerated.[https://www.sciencedirect.com/topics/neuroscience/ionophores]
'''Zinc Deficiency'''
Zinc deficiency has been demonstrated in some cancer cells, and returning optimum intra-cellular zinc levels can lead to suppression of tumor growth. Hinokitiol is a documented Zinc Ionophore; however, more research is required to establish effective concentrations of delivery methods for Hinokitiol and Zinc.
· “Effects of dietary zinc on melanoma growth and experimental metastasis...” [https://www.sciencedirect.com/science/article/abs/pii/0304383583902069]
· “Dietary zinc deficiency fuels esophageal cancer development by inducing a distinct inflammatory signature...” [https://www.nature.com/articles/onc2011592]
· “Zinc levels were relatively lower in patients with lung cancer as compared to a control group: a meta-analysis of observational studies...” [https://wjso.biomedcentral.com/articles/10.1186/s12957-019-1617-5]
· “Research progress on the relationship between zinc deficiency, related microRNA s, and esophageal carcinoma...” [https://onlinelibrary.wiley.com/doi/full/10.1111/1759-7714.12493]
Products containing Hinokitiol include toothpaste, oral sprays, sunscreen, and other cosmetics.
'''EWG Scoring Scale'''
Hinokitiol is also used in a wide range of consumer products, including cosmetics, toothpaste, oral sprays, sunscreens & hair-growth. One of the leading brands in the sale of consumer hinokitiol products is Hinoki Clinical. Hinoki Clinical (est. 1956) was established shortly after the first ‘industrial extraction of hinokitiol’ began in 1955.[https://www.hinoki.co.jp/products/hinokitiol/] Hinoki currently has over 18 different product ranges with hinokitiol as an ingredient. Another brand, namely, ‘Relief Life,’[https://www.anshin-tsuuhan.com/item/propogreen.html] , has boasted over a million sales with their ‘Dental Series’ toothpaste containing hinokitiol.[https://item.rakuten.co.jp/anshintsuuhan/10000015/] Other notable producers of hinokitiol based products include Otsuka Pharmaceuticals, Kobayashi Pharmaceuticals, Taisho Pharmaceuticals, SS Pharmaceuticals. Besides Asia, companies such as Swanson Vitamins®️ are commencing the utilization of hinokitiol in consumer products in markets such as the U.S.A.[https://www.swansonvitamins.com/now-foods-coq10-antioxidant-serum-1-fl-oz-liquid] and Australia [https://www.swansonaustralia.com/en/home/1033-now-foods-solutions-hyaluronic-acid-firming-serum-1-fl-oz-30ml.html] as an anti-oxidant serum and in other endeavors. In 2006, hinokitiol was categorized under the Domestic Substances List in Canada as non-persistent, non-bioaccumulative & non-toxic to aquatic organisms.[https://open.canada.ca/data/en/dataset/1d946396-cf9a-4fa1-8942-4541063bfba4] The Environmental Working Group (EWG), an American activist group, has dedicated a page to the ingredient hinokitiol indicating that it is ‘low hazard’ in areas such as “Allergies & Immunotoxicity,” “Cancer” & “Developmental & Reproductive Toxicity” [https://www.ewg.org/skindeep/ingredients/702859-HINOKITIOL/] giving Hinokitiol a score of 1-2. In contrast to Hinokitiol’s score, Propylparaben, an ingredient still sold in various mouthwashes, exhibits vast toxicity and hazardous concerns. Propylparaben has been deemed by the European Commission on Hormone Disruption to be a Human endocrine disruptor, among other concerns [https://www.ewg.org/skindeep/ingredients/705335-PROPYLPARABEN/] leaving it at a rating of 4-6 on the EWG website.
'''Dr. ZinX'''
On 2 April 2020, Advance Nanotek,[https://www.advancenanotek.com/] an Australian producer of zinc oxide, filed a joint patent application with AstiVita Limited,[https://www.astivita.com.au/] for an antiviral composition that included various oral care products [http://pericles.ipaustralia.gov.au/ols/auspat/applicationDetails.do?applicationNo=2020900820] containing hinokitiol as a vital component. The brand that is now incorporating this new invention is called Dr. ZinX and is likely to release its Zinc + Hinokitiol combination products in 2020.[https://www.asx.com.au/asxpdf/20200520/pdf/44hzh0v8bqgvlx.pdf][https://www.drzinx.com/] On 18 May 2020, Dr. ZinX published test results for a “Quantitative suspension test for the evaluation of hinokitol's virucidal properties in the medical area” [https://www.asx.com.au/asxpdf/20200520/pdf/44hzh0v8bqgvlx.pdf][https://www.drzinx.com/testresults] declaring a ‘3.25 log’ reduction (99.9% reduction) for a neat concentration in 5 minutes against COVID-19 surrogate Feline Coronavirus.[https://www.tga.gov.au/surrogate-viruses-use-disinfectant-efficacy-tests-justify-claims-against-covid-19] Zinc is considered to be an essential dietary supplement and trace element in the body. Globally it is estimated that 17.3% of the population has inadequate Zinc intake.[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510072/][https://academic.oup.com/jn/article/132/11/3422/4687273]
'''A Promising Future'''
Beginning in the 2000s, researchers considered that hinokitiol could be of value as a pharmaceutical ingredient, notably for its inhibitory effect on the bacterium ''Chlamydia trachomatis''.
Chemist Martin Burke and colleagues at the University of Illinois at Urbana–Champaign and other institutions discovered the significance of hinokitiol in the medical field. Burke’s goal was to overcome the imbalance of iron transport in animals. Deficiencies of several proteins can lead to iron deficiency in cells (anemia) or the opposite effect, Hemochromatosis.[https://www.acs.org/content/acs/en/molecule-of-the-week/archive/h/hinokitiol.html] Using gene-depleted yeast cultures as surrogates, the researchers screened a library of small biomolecules for iron transport signs and, therefore, cell growth. Hinokitiol was identified to be the one that rejuvenate cell's functionality. Further study by the team established the mechanism by which hinokitiol balances cell iron.[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470741/] They then diverted their study to mammals and found that when rodents that had been engineered to lack “iron proteins” were fed hinokitiol, they regained iron uptake by increasing the absorption in the gut. In a similar study on zebrafish, hinokitiol revealed to restore Hemoglobin production.[https://www.sciencemag.org/news/2017/05/iron-man-molecule-restores-balance-cells] A commentary on the work of Burke et al. nicknamed hinokitiol the “Iron Man molecule”. This is fitting/ironic because discoverer Nozoe’s first name can be translated into English as “iron man”.
Significant research has also been conducted into the oral applications of Hinokitiol, given the increased demand for Hinokitiol based oral products. One such study, affiliated with eight different institutions in Japan, titled: “Antibacterial Activity of Hinokitiol Against Both Antibiotic-Resistant and -Susceptible Pathogenic Bacteria That Predominate in the Oral Cavity and Upper Airways” concluded that “hinokitiol demonstrates antibacterial activity against a broad spectrum of pathogenic bacteria and has low cytotoxicity towards human epithelial cells.” [https://onlinelibrary.wiley.com/doi/abs/10.1111/1348-0421.12688]