| Drug ID: | D137 |
| Drug Name: | Fish oil |
| Synonyms: |
Fish oil containing omega-3 acids; Fish oils; Omega-3 fish oil
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| Type: | Biological drug |
| DrugBank ID: |
DB13961
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| DrugBank Description: |
Fish oil is a component of SMOFLIPID, which was FDA approved in July 2016. It is indicated in adults as a source of calories and essential fatty acids for parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated.
More commonly, fish oil refers to the omega-3-fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) . In general, dietary or pharmaceutical intake of these acids is primarily the only way to increase their levels in the human body where they are overall an essential element to dietary health as they have demonstrated abilities in minimizing or preventing hypertriglyceridemia when taken as an adjunct to a healthy diet .
Such fish oils are available in both non-prescription and prescription-only varieties at different concentrations. For many individuals, taking non-prescription fish oils as part of their multivitamin regimen is an effective way to supplement their diets with the healthy fatty acids. However, prescription-only fish oil products are sometimes prescribed for individuals who demonstrate severe (>= 500 mg/dL) hypertriglyceridemia .
Furthermore, a variety of studies regarding additional potential actions of fish oil omega-3-fatty acids EPA and DHA are ongoing. Such experimental actions include inflammation modulation, cardioprotective effects, the attenuation of oxidative stress, and more. Regardless, the specific mechanisms of action for these effects have yet to be formally elucidated.
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| PubChem ID: |
--
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| CasNo: |
8016-13-5
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| Repositioning for NAFLD: |
Yes
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| SMILES: |
--
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| InChiKey: |
--
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| Molecular Weight: |
--
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| DrugBank Targets: |
Diacylglycerol O-acyltransferase 2 agonist; Prostaglandin G/H synthase 2 inhibitor; Free fatty acid receptor 4 agonist&inhibits downstream inflammation cascades; Voltage gated L-type calcium channel inhibitor; Sodium channel protein inhibitor; Free radica
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| DrugBank MoA: |
The specific mechanism of action by which the fish oil EPA and DHA acids are capable of reducing serum triglyceride levels is not yet fully understood . Nevertheless, it is proposed that such omega-3-fatty acids may not be the preferred substrates of the enzyme diacylglycerol O-acyltransferase that participates in the generation of triglycerides; that they might interact with nuclear transcription factors that manage lipogenesis; or that their presence and increase in levels can cause cellular metabolism to subsequently shift toward a decrease in triglyceride synthesis and an increase in fatty acid oxidation . Moreover, the EPA and DHA acids are also believed to be able to promote apolipoprotein B degradation in the liver through the stimulation of an autophagic process . It may also be possible that these fish oil acids can accelerate the clearance of very-low-density lipoprotein (VLDL) particles and chylomicron . The combination of all these actions results in fewer VLDL particles being assembled and secreted, which is of considerable importance as VLDL particles are the major endogenous source of triglycerides .
Moreover, new paradigms of how inflammation is contained and dissipated involve various newly discovered chemical mediators, resolvins, and protectins . Such agents are believed to be directly involved in blocking neutrophil migration, infiltration, recruitment, as well as blocking T-cell migration and promoting T-cell apoptosis . Additionally, such protectins can also reduce tumor necrosis factor and interferon secretion . Of particular importance, however, is the fact that protectins and resolvins are exclusively derived from omega-3-fatty acids and that EPA is the substrate of the resolvins family and DHA can be converted to both resolvins and protectins . It is believed that these effects of such fish oil acids underlie the actions that fish oil have demonstrated on eliciting stability for vulnerable inflammatory plaques .
Finally, fish oil acids have demonstrated certain direct electrophysiological effects on the myocardium . In animal studies, it was shown that the ventricular fibrillation threshold could be increased in both animals fed or infused with omega-3-fatty acids . Further studies subsequently revealed that such fatty acids could reduce both sodium currents and L-type calcium currents on a cellular and ion channel level . It is consequently hypothesized that during ischemia, a reduction in the sodium ion current protects hyperexcitable tissue, and a reduction in the calcium ion current could reduce arrhythmogenic depolarizing currents - and that perhaps the use of EPA and DHA fish oil acids could facilitate such activity . For the time being, however, omega-3-fatty acids in pharmaceutical supplement form have not been shown to elicit such protection against heart conditions .
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| DrugBank Pharmacology: |
In general, the only practical method of obtaining and increasing the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) fish oil omega-3-fatty acids in the body is to consume them directly from foods and/or dietary supplements . Having EPA and DHA is important because they facilitate numerous important functions in the human body. As an example, such supplementation of fish oil EPA and DHA demonstrates a legitimate ability to decrease triglyceride levels as their presence in the body can act as poor substrates for the enzymes that are ordinarily responsible for triglyceride synthesis and also inhibit the esterification of other fatty acids, among other mechanisms .
Moreover, such fish oil acids can become important components of the phospholipids that form the structures of cell membranes . Specifically, DHA is particularly high in the retina, brain, and sperm . Additionally, these acids also provide energy for the body and are used to form eicosanoids - signaling molecules that have similar chemical structures to the fish oil fatty acids from which they are derived . Furthermore, such eicosanoids possess wide-ranging functions in the cardiovascular, pulmonary, immune, and endocrine systems .
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| DrugBank Indication: |
Under FDA approval, fish oil pharmaceuticals are typically products consisting of a combination of the omega-3-fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and are indicated primarily as an adjunct to diet to reduce triglyceride levels in adult patients with severe (>=500 mg/dL) hypertriglyceridemia .
Under EMA approval, such fish oil pharmaceuticals comprised of virtually the same fish and fish oil derived omega-3-fatty acids EPA and DHA are indicated specifically for (a) adjuvant treatment in secondary prevention after myocardial infarction, in addition to other standard therapy (ie. statins, antiplatelet medicinal products, beta blockers, ACE inhibitors), and (b) as a supplement to diet when dietary measures alone are insufficient to produce an adequate response, particularly with type IV hypertriglyceridemia in monotherapy or type IIb/III in combination with statins, when control of triglycerides is insufficient . In addition, prescribing information for EMA approved fish oil pharmaceuticals are also indicated as an adjunct to diet to reduce very high (>=500 mg/dL) triglyceride levels in adult patients, much like similar FDA approved indications .
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| Targets: |
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| Therapeutic Category: |
--
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| Clinical Trial Progress: |
Phase 2&3 completed (NCT00681408: N-3 PUFAs at 3000 mg/day for one year did not lead to an improvement in the primary outcome of histological activity in NASH patients (⩾ 2 point NAS reduction). N-3 led to reduced liver fat by multiple measures. Other metabolic effects were not seen, although no detrimental effects were apparent. Whether longer duration, higher dose, or different composition of n-3 therapy would lead to additional benefits is uncertain.)
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| Latest Progress: |
Under clinical trials
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