Epastigel®
EPASTIGEL®
Active Pharmaceutical Ingredient: Ultraconcentrated Eicosapentaenoic Acid (EPA)
Dosage Form: Softgel 500 & 1000 mg
Administration Route: Oral
Number/Bottle: 28
Indications: Cardiovascular Diseases Risk Reduction, Severe Hypertriglyceridemia, Hepatic Impairment Risk Reduction, Help to Support Joints & Muscles, Maintain Mental & Neuronal Health, etc.
Mechanism of Action: Omega-3 fatty acids mediate anti-inflammatory effects and increased levels of EPA or DHA has shown to decrease the levels of PGE2 and 4 series-LT. Eicosapentaenoic acids compete with constitutive levels of arachidonic acid in cell membranes for the same desaturation enzymes and produce 3-series prostaglandins and thromboxanes, and 5-series leukotrienes which have low pro-inflammatory potential. The alteration in leukotriene biosynthesis due to a higher concentration of omega-3 fatty acids compared to arachidonic acid underlies the anti-inflammatory effects. EPA and DHA also give rise to resolvins and related lipid signaling molecules such as protectins via cyclooxygenase and lipoxygenase pathways, which have anti-inflammatory effects. They inhibit transendothelial migration of neutrophils and inhibit TNF and IL-1β production. Omega-3 fatty acids also decrease adhesion molecule expression on leukocytes and endothelial cells and decrease intercellular adhesive interactions. Omega-3 (or n-3) polyunsaturated fatty acids (PUFAs) and their metabolites are natural ligands for peroxisome proliferator-activated receptor (PPAR) gamma that regulates inflammatory gene expression and NFκB activation. PPAR alpha activation is also associated with the induction of COX-2 expression. The role of EPA and DHA in reducing triglyceride levels include inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase, increased mitochondrial and peroxisomal-beta-oxidation in the liver, decreased lipogenesis in the liver and increased plasma lipoprotein lipase activity. They also may reduce triglyceride synthesis because they are poor substrates for the enzymes responsible for TG synthesis, and EPA and DHA inhibit the esterification of other fatty acids.
Omega-3 Fatty Acids: An Essential Contribution
The human body can make most of the types of fats it needs from other fats or raw materials. That isn’t the case for omega-3 fatty acids (also called omega-3 fats and n-3 fats). These are essential fats—the body can’t make them but must get them from food. Food high in Omega-3 include fish, vegetable oils, nuts (especially walnuts), flax seeds, flaxseed oil, and leafy vegetables.
What makes omega-3 fats special?
They are an integral part of cell membranes throughout the body and affect the function of the cell receptors in these membranes. They provide the starting point for making eicosanoids and hormones that regulate blood clotting, contraction and relaxation of artery walls, and inflammation. They also bind to receptors in cells that regulate genetic function. Likely due to these effects, omega-3 fats have been shown to help prevent heart disease and stroke, may help control lupus, eczema, and rheumatoid arthritis, and may play protective roles in cancer and other conditions.
Omega-3 fats are a key family of polyunsaturated fats. There are three main omega-3s:
- Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) come mainly from fish, so they are sometimes called marine omega-3s.
- Alpha-linolenic acid (ALA), the most common omega-3 fatty acid in most Western diets, is found in vegetable oils and nuts (especially walnuts), flax seeds and flaxseed oil, leafy vegetables, and some animal fat, especially in grass-fed animals. The human body generally uses ALA for energy, and conversion into EPA and DHA is very limited.
The strongest evidence for the beneficial effect of omega-3 fats has to do with heart disease. These fats appear to help the heart beat at a steady clip and not veer into a dangerous or potentially fatal erratic rhythm. Such arrhythmias cause most of the 500,000-plus cardiac deaths that occur each year in the United States. Omega-3 fats also lower blood pressure and heart rate, improve blood vessel function, and, at higher doses, lower triglycerides and may ease inflammation, which plays a role in the development of atherosclerosis.
Several large trials have evaluated the effect of fish or fish oils on heart disease. In the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardio (known as the GISSI Prevention Trial), heart attack survivors who took a 1-gram capsule of omega-3 fats every day for three years were less likely to have a repeat heart attack, stroke, or die of sudden death than those who took a placebo. Notably, the risk of sudden cardiac death was reduced by about 50 percent. In the more recent Japan EPA Lipid Intervention Study (JELIS), participants who took EPA plus a cholesterol-lowering statin were less likely to have a major coronary event (sudden cardiac death, fatal or nonfatal heart attack, unstable angina, or a procedure to open or bypass a narrowed or blocked coronary artery) than those who took a statin alone.
Most Americans take in far more of another essential fat—omega-6 fats—than they do omega-3 fats. Some experts have raised the hypothesis that this higher intake of omega-6 fats could pose problems, cardiovascular and otherwise. Many other studies and trials in humans also support the cardiovascular benefits of omega-6 fats. Although there is no question that many people could benefit from increasing their intake of omega-3 fats, there is evidence that omega-6 fats also positively influence cardiovascular risk factors and reduce heart disease.
Researchers are taking a hard look at a different sort of balance, this one between possible effects of marine and plant omega-3 fats on prostate cancer. Results from the Health Professionals Follow-up Study and others show that men whose diets are rich in EPA are less likely to develop advanced prostate cancer than those with a low intake of EPA. At the same time, some but not all studies show an increase in prostate cancer and advanced prostate cancer among men with high intakes of ALA (mainly from supplements).
Given the wide-ranging importance and benefits of marine omega-3 fatty acids, it is important to take EPA-rich omega-3 fatty acids or seafood two to three times a week, particularly fatty (dark meat) fish that are richer in EPA and DHA. This is especially important for women who are pregnant or hoping to become pregnant and nursing mothers. From the third trimester until the second year of life, a developing child needs a steady supply of DHA to form the brain and other parts of the nervous system. Many women are cautious about eating seafood because of fears that mercury and other possible contaminants might harm their babies, yet the evidence for harm from lack of omega-3 fats is far more consistent, and a balance of benefit vs. risk is easily obtained. This table lists common to fish and seafood products and their omega-3 fatty acid content.
|
Type of Seafood |
Omega-3 Fatty Acids (mg/100 g fish) |
|
Anchovy |
2117 |
|
Catfish (farmed) |
180 |
|
Clams |
282 |
|
Cod (Atlantic) |
127 |
|
Crab |
412 |
|
Fish sticks (frozen) |
204 |
|
Halibut |
466 |
|
Lobster |
86 |
|
Mahi |
112 |
|
Mussels |
672 |
|
Oysters |
684 |
|
Pollock (Alaskan) |
446 |
|
Salmon (wild) |
863 |
|
Sardines |
912 |
|
Scallops |
351 |
|
Shrimp |
292 |
|
Swordfish* |
700 |
|
Trout |
680 |
|
Tuna (albacore)** |
780 |
|
Tuna (light, skipjack) |
256 |
SOURCE: Mozaffarian D, Rimm EB. JAMA. 2006; 296:1885-1899.
*Swordfish contains high levels of mercury, as does shark, king mackerel, and tilefish (sometimes called golden bass or golden snapper). Women who are or may become pregnant, nursing mothers, and young children should avoid these high-mercury species of fish but can eat up to 12 ounces (two average meals) a week of a variety of fish and shellfish that are lower in mercury.
**Albacore tuna contains more mercury than canned, light tuna. Women who are or may become pregnant, nursing mothers, and young children should limit albacore tuna to one serving per week.
As you can see in the table above, anchovy fish is the best source for EPA extraction due to its high amount of omega-3 and its short lifespan. The 20-day life of this fish does not allow the accumulation of heavy metals, especially mercury, in fish oil. EPA is taken by mouth for some heart-related conditions including congestive heart arteries (coronary artery disease), to prevent or treat heart attacks, and to reduce levels of blood fats called triglycerides in people with very high levels. It is also used for some mental conditions including schizophrenia, personality disorders, Alzheimer’s disease, depression, and attention deficit hyperactivity disorder (ADHD). It is also used to prevent loss of vision that occurs in older people (age-related macular degeneration; AMD), psoriasis, asthma, cystic fibrosis, and diabetes. EPA is also used to prevent lung cancer, and prostate cancer, to help maintain body weight in people with cancer, and to reduce the side effects of chemotherapy in patients with cancer.
Women use EPA to reduce symptoms of menopause, to reduce high blood pressure during high-risk pregnancies, and to reduce the risk of an infant having delayed growth while still in the uterus.
EPA is used for a variety of conditions, including preventing and reversing heart disease, and decreasing irregular heartbeats; as well as asthma, cancer, menstrual problems, hot flashes, hay fever, lung diseases, lupus, and kidney disease caused by an immune reaction. The combination is also used for migraine headache prevention in adolescents, skin infections, Behçet’s syndrome, high cholesterol, high blood pressure, psoriasis, Raynaud’s syndrome, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis.
EPA is used in combination with L-arginine after surgery to reduce infections, improve wound healing, and shorten recovery time. It is also used in combination with another fatty acid, gamma-linolenic acid, for high blood pressure.
Don’t confuse EPA with similar fatty acids, such as alpha-linolenic acid and DHA, as well as with oils like krill or fish oils, which contain both eicosapentaenoic acid and docosahexaenoic acid. EPA is the potent component of fish oil and the therapeutic effects of EPA were approved by FDA in 2019.
Uses
- High levels of blood fats called triglycerides (hypertriglyceridemia). Research shows that taking a specific product containing eicosapentaenoic acid (Vascepa by Amarin) by mouth along with dieting and cholesterol-lowering drugs called “statins” reduces levels of triglycerides in people with very high levels. It might also improve cholesterol levels. This product is FDA-approved in adults with very high triglyceride levels.
Possibly Effective for…
- Clogged heart arteries (coronary artery disease). People with coronary artery disease who consume more eicosapentaenoic acid as part of the diet seem to have a slightly reduced risk of death. Early research shows that taking 1800 mg of eicosapentaenoic acid daily reduces the risk of heart-related adverse events such as heart attacks in people with high cholesterol and coronary artery disease.
- Depression. Research suggests that taking pure eicosapentaenoic acid or fish oil containing at least 60% eicosapentaenoic acid reduces symptoms of depression. It might work best when used along with antidepressant drugs. Taking eicosapentaenoic acid also seems to help prevent depression from developing in people being treated with a drug called interferon-alpha.
- Symptoms of the menopause. Research shows that taking eicosapentaenoic acid reduces how often hot flashes occur. But eicosapentaenoic acid does not seem to reduce the intensity of the hot flashes or improve the overall quality of life.
- A mood disorder called borderline personality disorder. Taking eicosapentaenoic acid seems to slightly lower aggressiveness and slightly relieve depression in women with this mood disorder.