Editing Essential tremor (section)

==Research==
[[Harmaline]] is a widely used model of essential tremor (ET) in rodents.<ref name="pmid17366267">{{cite journal | vauthors = Miwa H | title = Rodent models of tremor | journal = Cerebellum | volume = 6 | issue = 1 | pages = 66–72 | year = 2007 | pmid = 17366267 | doi = 10.1080/14734220601016080 | s2cid = 24179439 }}</ref> Harmaline is thought to act primarily on neurons in the [[inferior olivary nucleus|inferior olive]]. Olivocerebellar neurons exhibit rhythmic excitatory action when harmaline is applied locally.<ref name="pmid17366267"/> [[Harmane]] or harmaline has been implicated not only in essential tremors, but is also found in greater quantities in the brain fluid of people with Parkinson's disease and [[cancer]].<ref name=pmid9029410>{{cite journal | vauthors = Kuhn W, Müller T, Grosse H, Rommelspacher H | title = Elevated levels of harman and norharman in cerebrospinal fluid of parkinsonian patients | journal = Journal of Neural Transmission | volume = 103 | issue = 12 | pages = 1435–1440 | year = 1996 | pmid = 9029410 | doi = 10.1007/bf01271257 | s2cid = 21230301 }}</ref><ref name=pmid15036003>{{cite journal | vauthors = Pfau W, Skog K | title = Exposure to beta-carbolines norharman and harman | journal = Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences | volume = 802 | issue = 1 | pages = 115–126 | date = March 2004 | pmid = 15036003 | doi = 10.1016/j.jchromb.2003.10.044 | doi-access = free }}</ref><ref name=pmid18709680>{{cite journal | vauthors = Louis ED, Pellegrino KM, Factor-Litvak P, Rios E, Jiang W, Henchcliffe C, Zheng W | title = Cancer and blood concentrations of the comutagen harmane in essential tremor | journal = Movement Disorders | volume = 23 | issue = 12 | pages = 1747–1751 | date = September 2008 | pmid = 18709680 | pmc = 2597456 | doi = 10.1002/mds.22084 }}</ref> Higher levels of the [[neurotoxin]] are associated with greater severity of the tremors.<ref name=pmid17679670>{{cite journal | vauthors = Louis ED, Zheng W, Mao X, Shungu DC | title = Blood harmane is correlated with cerebellar metabolism in essential tremor: a pilot study | journal = Neurology | volume = 69 | issue = 6 | pages = 515–520 | date = August 2007 | pmid = 17679670 | doi = 10.1212/01.wnl.0000266663.27398.9f | s2cid = 7612446 }}</ref><ref name=pmid21145352>{{cite journal | vauthors = Louis ED, Factor-Litvak P, Gerbin M, Slavkovich V, Graziano JH, Jiang W, Zheng W | title = Blood harmane, blood lead, and severity of hand tremor: evidence of additive effects | journal = Neurotoxicology | volume = 32 | issue = 2 | pages = 227–232 | date = March 2011 | pmid = 21145352 | pmc = 3073713 | doi = 10.1016/j.neuro.2010.12.002 | bibcode = 2011NeuTx..32..227L }}</ref> Harmane is particularly abundant in meats, and certain cooking practices (e.g., long cooking times) increase its concentration,<ref name=pmid22757671>{{cite journal | vauthors = Louis ED, Jiang W, Gerbin M, Viner AS, Factor-Litvak P, Zheng W | title = Blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor: repeat observation in cases and controls in New York | journal = Journal of Toxicology and Environmental Health. Part A | volume = 75 | issue = 12 | pages = 673–683 | year = 2012 | pmid = 22757671 | pmc = 3412610 | doi = 10.1080/15287394.2012.688485 | bibcode = 2012JTEHA..75..673L }}</ref><ref name=pmid17497412>{{cite journal | vauthors = Louis ED, Zheng W, Jiang W, Bogen KT, Keating GA | title = Quantification of the neurotoxic beta-carboline harmane in barbecued/grilled meat samples and correlation with level of doneness | journal = Journal of Toxicology and Environmental Health. Part A | volume = 70 | issue = 12 | pages = 1014–1019 | date = June 2007 | pmid = 17497412 | pmc = 4993204 | doi = 10.1080/15287390601172015 | bibcode = 2007JTEHA..70.1014L }}</ref><ref name=pmid18382115>{{cite journal | vauthors = Louis ED, Keating GA, Bogen KT, Rios E, Pellegrino KM, Factor-Litvak P | title = Dietary epidemiology of essential tremor: meat consumption and meat cooking practices | journal = Neuroepidemiology | volume = 30 | issue = 3 | pages = 161–166 | year = 2008 | pmid = 18382115 | pmc = 2821442 | doi = 10.1159/000122333 }}</ref> but at least one study has shown that harmane blood concentrations do not go up after meat consumption in ET patients with already elevated harmane levels, whereas the control group's harmane levels increase accordingly, suggesting that another factor, such as a metabolic defect, may be responsible for the higher harmane levels in ET patients.<ref>{{cite journal | vauthors = Louis ED, Zheng W, Applegate L, Shi L, Factor-Litvak P | title = Blood harmane concentrations and dietary protein consumption in essential tremor | journal = Neurology | volume = 65 | issue = 3 | pages = 391–396 | date = August 2005 | pmid = 16087903 | pmc = 4993192 | doi = 10.1212/01.wnl.0000172352.88359.2d }}</ref>

[[Caprylic acid]] is being researched as a possible treatment for essential tremor. It has currently been approved by the FDA and designated as GRAS, and is used as a food additive and has been studied as part of a ketogenic diet for treatment of epilepsy in children. Research on caprylic acid as a possible treatment for ET began because researchers recognized that ethanol was effective in reducing tremor, and because of this, they looked into longer-chain alcohols reducing tremor. They discovered that [[1-Octanol|1-octanol]] reduced tremor and did not have the negative side effects of ethanol. Pharmacokinetic research on 1-octanol lead to the discovery that 1-octanol metabolized into caprylic acid in the body and that caprylic acid actually was the tremor-reducing agent.<ref>{{cite journal | vauthors = Haubenberger D, McCrossin G, Lungu C, Considine E, Toro C, Nahab FB, Auh S, Buchwald P, Grimes GJ, Starling J, Potti G, Scheider L, Kalowitz D, Bowen D, Carnie A, Hallett M | title = Octanoic acid in alcohol-responsive essential tremor: a randomized controlled study | journal = Neurology | volume = 80 | issue = 10 | pages = 933–940 | date = March 2013 | pmid = 23408867 | pmc = 3653213 | doi = 10.1212/WNL.0b013e3182840c4f }}</ref> Many studies of the effects of caprylic acid on essential tremor have been done, including a dose-escalation study on ET patients<ref>{{cite journal | vauthors = Voller B, Lines E, McCrossin G, Tinaz S, Lungu C, Grimes G, Starling J, Potti G, Buchwald P, Haubenberger D, Hallett M | title = Dose-escalation study of octanoic acid in patients with essential tremor | journal = The Journal of Clinical Investigation | volume = 126 | issue = 4 | pages = 1451–1457 | date = April 2016 | pmid = 26927672 | pmc = 4811161 | doi = 10.1172/JCI83621 }}</ref> and a study testing the effects of caprylic acid on central and peripheral tremor.<ref name="Cao_2018" /> The dose-escalation study examined doses of 8&nbsp;mg/kg to 128&nbsp;mg/kg and determined that these concentrations were safe with mild side effects. The maximum tolerated dose was not reached in this study. The study testing the effects of caprylic acid on central and peripheral tremors determined that caprylic acid reduced both.