CHAMPAIGN, Ill. — Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its euphoric effects, but it also has anti-inflammatory benefits. A new study in animal tissue reveals the cascade of chemical reactions that convert omega-3 fatty acids into cannabinoids that have anti-inflammatory benefits – but without the psychotropic high.
AD is a devastating disease for which there are limited treatment options and no cure. Memory loss is an early indicator of the disease, which is progressive, and leads to the inability of the patient to care for him- or herself and eventually to death (47). Currently, the number of individuals with AD is estimated to be 26.6 million and is expected to increase to 106.2 million by 2050 (48). There have been many studies conducted regarding the use of omega-3 fatty acid supplementation and AD (Table 2). DHA is present in large amounts in neuron membrane phospholipids, where it is involved in proper function of the nervous system, which is why it is thought to play a role in AD (49). A case-control study consisting of 148 patients with cognitive impairment [Mini-Mental State Examination (MMSE) score <24] and 45 control patients (MMSE score ≥24) showed that serum cholesteryl ester-EPA and -DHA levels were significantly lower (P < 0.05 and P < 0.001, respectively) in all MMSE score quartiles of patients with AD compared with control values (49). Another study found that a diet characterized by higher intakes of foods high in omega-3 fatty acids (salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, dark and green leafy vegetables), and a lower intake of foods low in omega-3 fatty acids (high-fat dairy products, red meat, organ meat, butter) was strongly associated with a lower AD risk (50). Image analysis of brain sections of an aged AD mouse model showed that overall plaque burden was significantly reduced by 40.3% in mice with a diet enriched with DHA (P < 0.05) compared with placebo. The largest reductions (40–50%) were seen in brain regions that are thought to be involved with AD, the hippocampus and parietal cortex (51). A central event in AD is thought to be the activation of multiple inflammatory cells in the brain. Release of IL-1B, IL-6, and TNF α from microglia cells may lead to dysfunction of the neurons in the brain (52). In 1 study, AD patients treated with EPA+DHA supplementation increased their plasma concentrations of EPA and DHA, which were associated with reduced release of inflammatory factors IL-1B, IL-6, and granulocyte colony–stimulating factor from peripheral blood mononuclear cells (53).
In our analysis, most of the included studies showed a positive Hedges g toward a beneficial effect of omega-3 PUFAs in anxiety reduction, although not all findings were statistically significant. However, after merging of these effect sizes from all of the included studies, the main result showed significant findings in our meta-analysis. Despite the significant heterogeneity, no significant publication bias was found among these 19 studies.
The biggest cause of omega-3 deficiency is the overconsumption of foods high in omega-6 fatty acids. Omega-6 comes from things like fried foods, fast foods and boxed foods that contain vegetables oils like soybean oil, canola oil, sunflower oil, cottonseed oil and corn oil. When you consume too much omega-6, it can decrease your body’s ability to metabolize healthy omega-3 fatty acids. (36)
Foods such as meat, eggs, fish and nuts contain omega-3 and omega-6 fatty acids, which the body converts into endocannabinoids – cannabinoids that the body produces naturally, said Aditi Das, a University of Illinois professor of comparative biosciences and biochemistry, who led the study. Cannabinoids in marijuana and endocannabinoids produced in the body can support the body’s immune system and therefore are attractive targets for the development of anti-inflammatory therapeutics, she said.
Fish oil is oil derived from the tissues of oily fish. Fish oils contain the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), precursors of certain eicosanoids that are known to reduce inflammation in the body, and have other health benefits, such as treating hypertriglyceridemia, although claims of preventing heart attacks or strokes have not been supported. Fish oil and omega-3 fatty acids have been studied in a wide variety of other conditions, such as clinical depression, anxiety, cancer, and macular degeneration, yet benefits in these conditions have not been verified.
Because of the preliminary state of knowledge on the effects of omega-3 PUFA treatment on anxiety, we decided to include as many studies as possible and not to set further limitations on specific characteristics, such as length of study, diagnosis, omega-3 PUFA dosage, omega-3 PUFA preparation (EPA to DHA ratio), rated anxiety coding scale, or type of control. Therefore, we chose to make the inclusion criteria as broad as possible to avoid missing any potentially eligible studies. The inclusion criteria included clinical trials in humans (randomized or nonrandomized), studies investigating the effects of omega-3 PUFA treatment on anxiety symptoms, and formal published articles in peer-reviewed journals. The clinical trials could be placebo controlled or non–placebo controlled. The target participants could include healthy volunteers, patients with psychiatric illness, and patients with physical illnesses other than psychiatric illnesses. The exclusion criteria included case reports or series, animal studies or review articles, and studies not investigating the effects of omega-3 PUFA treatment on anxiety symptoms. We did not set any language limitation to increase the number of eligible articles. Figure 1 shows the literature search and screening protocol.
We are now fortunate to understand how these fats work in combination and in isolation, how they are digested, absorbed and utilised in the body, so we are able to tailor different blends of EPA and DHA according to the health benefits we are seeking to achieve. At Igennus, we have long specialised in the role of the omega-3 fatty acid EPA in clinical nutrition, as a powerful tool in the patient’s ‘toolkit’ for helping to regulate inflammation by restoring several biological markers, known as the omega-6 to omega-3 ratio and AA to EPA ratio. Before we discuss the therapeutic role of EPA in nutritional medicine, here’s a very brief summary of the role of both EPA and DHA in health throughout life.
EPA, which is eicosapentaenoic acid, and DHA, which is docosahexaenoic acid, are two types of omega-3 fatty acids that are most commonly found in seafood. These polyunsaturated fats are known to have preventative health benefits and have been studied for their role in treating certain chronic conditions. In addition to dietary sources, certain supplements such as fish oil, are also rich in EPA and DHA.
An animal study involving the omega-3 ETA discovered that subjects experienced a drop in overall inflammation similar to that caused by NSAIDs (non-steroidal anti-inflammatory drugs), but without the dangerous gastrointestinal side effects. The study authors also pointed out that eicosapentaenoic acid seems to be even more potent than the conventional omega-3s found in fish oil supplements (EPA/DHA). (56)
Dry eye. Some clinical research shows that eating more fish oil is linked to a lower risk of getting dry eye syndrome in women. Other research shows that taking a specific fish oil product (PRN Dry Eye Omega Benefits softgels) daily modestly improves symptoms of dry eye such as pain, blurred vision, and sensitivity. Other research using other forms of fish oil products suggests that taking these supplements for 4-12 weeks modest improves some dry eye symptoms. However, the sensation of eye dryness is not always improved. Other research also shows that taking a specific combination products containing fish oil and other ingredients might improve some dry eye symptoms; however, this research is conflicted and poor quality.
The current American diet has changed over time to be high in SFA and low in omega-3 fatty acids (12). This change in eating habits is centered on fast food containing high amounts of saturated fat, which has small amounts of essential omega-3 PUFA compared with food prepared in the home (13). Seafood sources such as fish and fish-oil supplements are the primary contributors of the 2 biologically important dietary omega-3 fatty acids, EPA and DHA (14–16). This low intake of dietary EPA and DHA is thought to be associated with increased inflammatory processes as well as poor fetal development, general cardiovascular health, and risk of the development of Alzheimer's disease (AD).
Lok CE, Moist L, Hemmelgarn BR, Tonelli M, Vazquez MA, Dorval M, Oliver M, Donnelly S, Allon M, Stanley K; Fish Oil Inhibition of Stenosis in Hemodialysis Grafts (FISH) Study Group. Effect of fish oil supplementation on graft patency and cardiovascular events among patients with new synthetic arteriovenous hemodialysis grafts: a randomized controlled trial. JAMA 2012;307(17):1809-16. View abstract.
Most leafy green vegetables have significant amounts of omega-3, and spinach is no exception. Despite its villainous reputation, raw spinach actually has a mild flavor, making it an ideal base for salads or a crunchy addition to sandwiches. Many people add spinach to eggs, soups, or pasta dishes without impacting flavor. If you’re dealing with a particularly picky eater, though, try some of the recipes in Jessica Seinfeld’s Deceptively Delicious — her spinach and carrot brownies are tasty, healthy, and chocolaty to boot!
Good points, Miroslav. Focusing on your 4th point, with so many different formulations on the market that contain various preservatives, only looking at the blood levels of omega-3’s as the flag for increased risk for prostate cancer tends to ignore the fact that certain populations in coastal regions maintain a diet high in omega fish oils and don’t have a marked increase level of prostate cancer, pointing to the fact that another agent may be to blame here.
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So back to fish oil in general. The major fish oil benefits include decreasing the risk of heart disease and stroke while also helping reduce symptoms of depression, hypertension, attention deficit hyperactivity disorder (ADHD), joint pain, arthritis and chronic skin ailments like eczema. (2) Fish oil intake has also been associated with aiding the body in weight loss, fertility, pregnancy and increased energy. Prescription fish oil has even been approved by the FDA to lower unhealthy high triglyceride levels. (3)
A lot of the benefit of fish oil seems to come from the omega-3 fatty acids that it contains. Interestingly, the body does not produce its own omega-3 fatty acids. Nor can the body make omega-3 fatty acids from omega-6 fatty acids, which are common in the Western diet. A lot of research has been done on EPA and DHA, two types of omega-3 acids that are often included in fish oil supplements.