Omega-3 Recommendations: Counseling Points for Pharmacists
Fish oil supplements come in various dosage forms or combinations. A target dose of around 1 g of omega-3s is a good place to start. 4 When taking fish oil supplements, patients may experience an unpleasant “fishy” taste; however, the use of higher-quality products with a United States Pharmacopeia seal may alleviate this problem, as these products may be less likely to have the unpleasant taste or smell. 5 Patients may also be advised to store the capsules in the refrigerator or to take them at bedtime to avoid the unpleasant taste.
Fish oil supplements are a common source of DHA and EPA. For individuals who cannot tolerate fish oil, or do not wish to take it, omega-3s are also contained in krill, cod liver, and algal oil supplements.
The primary vehicle for EPA and DHA to enter the body is through the consumption of fish and other seafood, so the American Heart Association recommends consuming 2 servings of fish per week, particularly fatty fish such as tuna, salmon, herring, or sardines, which have high levels of omega-3s. 1,3 For patients who do not get enough omega-3s through their diet or who require a higher level than what their diet provides, OTC and prescription dietary supplements of omega-3s may help to meet their daily needs.
Omega-3 fatty acids have 2 main components that are beneficial in humans: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). DHA levels are highest in the retina and brain. Omega-3s can also be used to form eicosanoids, which have activity in the cardiovascular, pulmonary, immune, and endocrine systems. A third component of omega-3s, alpha-linolenic acid (ALA), is not active in the body, but it can be converted to EPA and DHA. 1,2
Omega-3 fatty acids (omega-3s) have received much publicity and advertising attention over the last few years stating that they are an essential supplement many people should consider taking. As a pharmacist, it is important to know which patients may benefit from omega-3 supplements the most, the supplements’ proper dosage, and the benefits that can be expected. It is also important to know which health claims about omega-3s have the most validity. OMEGA-3
Krill oil, sourced from tiny crustaceans called krill, can be an alternative for patients who cannot tolerate the fishy smell or taste that can be associated with fish oil supplements. Krill oil is more stable than fish oil, which may mean it is absorbed better, and because it is not sourced from fish, it may be less likely to cause a fishy aftertaste. The use of krill oil has not been studied as extensively as that of fish oil, however, and probably should remain as a secondary recommendation until further research reinforces its safety and effectiveness. The recommended dosage from the manufacturer will be included on the krill oil product that is selected.6
For those patients who follow a vegetarian or vegan diet, pharmacists may recommend an algal oil supplement to add omega-3s to their diet. Algal oil is derived from algae and may be a good source of EPA and DHA; however, studies on algal oil have not been extensive.7,8 Recommendations of these products may need to be limited to only those patients who cannot tolerate fish oil or those patients who do not consume any fish products because of dietary preferences or needs. Pharmaceutical-grade omega-3 products are also available and are prescribed in dosages as high as 4 g per day. These products are indicated for patients with very high triglyceride levels.9 Patients should be advised to not take dosages in this range through OTC products without the advice of their physician.
BENEFITS OF OMEGA-3s
The efficacy of omega-3s in various conditions has been researched extensively, sometimes with conflicting results. Several trials have been conducted researching the link between a diet rich in omega-3s and a decreased risk of cardiovascular disease.9 Although these data vary across studies, the FDA states that there is supportive (but not conclusive) research indicating that consumption of EPA and DHA may reduce the risk of coronary heart disease.9
DHA is important for fetal growth and is found in high concentrations in the cellular membranes of the brain and the retina, and so many prenatal vitamins and infant formulas are fortified with DHA. Omega-3s have anti-inflammatory properties, and their use may provide some relief from mild inflammation or joint pain as well as help to reduce patients’ reliance on nonsteroidal antiinflammatory drugs for inflammation.10
Many other benefits claimed for omega-3s have been studied but have been proved inconclusive. These include potential benefits studied in patients with dementia, depression, and attention deficit/hyperactivity disorder, as well as cancer prevention.9 Continued research is needed to try to uncover additional benefits or to confirm the validity of other perceived advantages of a diet rich in omega-3s.
RECOMMENDED DOSES
According to Dietary Guidelines for Americans 2015-2020, the goal for most Americans should be to consume 8 oz of seafood per week, which is about 250 mg of EPA and DHA per day.11 For those patients who are looking for more advanced benefits from omega-3s, pharmacists may recommend a total dose of 1 g per day via supplements.4 Patients with very high levels of triglycerides can be prescribed doses as high as 4 g per day while under supervision of a physician.9
The Institute of Medicine published a guideline in 2005 for intake of total omega-3s for infants and of ALA for children and adults, which is still used by the National Institutes of Health today (see table).2
CONCLUSIONS
The use of omega-3 supplements may be beneficial for some patients; however, the most effective way to add omega-3s to the diet is by consuming them through food. Pharmacists may recommend 2 servings of fatty fish per week to patients as a starting point, which will not only introduce the beneficial EPA and DHA components into the diet but may also replace foods or meals that are not as healthy. For patients who are unwilling or unable to eat fish every week, other foods that are rich in omega-3s, such as flaxseeds, walnuts, Brussels sprouts, soybeans, or seaweed, can be recommended. Omega-3 supplements such as fish oil, krill oil, or algal oil are the next alternative for patients who cannot consume enough omega-3s from their diet. Pharmacists should be prepared to answer questions about omega-3 supplementation and know which types of patients could benefit from them the most. Educating patients on the reasoning for a recommendation and encouraging them to discuss recommendations with their physician will go a long way in ensuring positive outcomes.
BRADY COLE, RPH, is pharmacy manager at Tom Thumb Pharmacy in Plano, Texas, and an active preceptor at Texas Tech University and the University of Houston. He is also the founder of the website Helpful Pharmacist
REFERENCES
Fish Oil and Omega-3 Fatty Acids
Omega-3 fatty acids are a popular food supplement believed to have positive effects on heart health. This stems mainly from observational studies showing that people consuming large amount of fish have lower rates of heart disease. Therefore, the American Heart Association recommends eating at least two servings of preferably fatty fish a week. Each serving is 3.5 ounce cooked, or about ¾ cup of flaked fish. Omega-3 fatty acids are thought to improve heart health by lowering triglycerides, raising good cholesterol (HDL, or high density lipoprotein), thinning the blood to prevent blood clots from forming and protecting the heart from dangerous heart rhythms.
Omega-3 fatty acids also may slow the progression of plaque buildup and lower blood pressure. Omega-3 fatty acids are highly concentrated in the brain and may be important for cognitive (brain memory and performance) and behavioral function. Scientists believe the omega-3 fatty acid DHA may be protective against Alzheimer's disease and dementia. In Italy, omega-3s are given routinely to heart attack patients. They are also used in other fields of medicine, because omega-3 fish oils are thought to have anti-inflammatory effects.
Sources of Omega-3 Fatty Acids
Omega-3 fatty acids are considered essential fatty acids; this means they are essential to health but cannot be produced by the body. Three different forms of omega-3 fatty acids exist: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and alpha-linolenic acid (ALA). ALA is found in plant sources (flaxseed oil) and food (flaxseeds, walnuts, tofu). EPA and DHA come from seafood, especially fatty fish such as salmon, tuna and halibut. Although fish is a source of omega-3s, fish themselves do not produce them. Rather, they are obtained from the algae (microalgae in particular) and plankton consumed in their diets.
Fish EPA Content
(G/100 G) DHA Content
(G/100 G) EPA + DHA
(G/100 G) Salmon (Atlantic)
Mackerel
Tuna (fresh)
Trout (Rainbow)
Tuna (canned)
Sworfish
Sea Bass
Flounder
Halibut
Crab (Alaskan King)
Shrimp
Catfish (farmed)
Cod 0.690
0.504
0.283
0.334
0.233
0.138
0.206
0.243
0.091
0.295
0.171
0.049
0.004 1.457
0.699
0.890
0.820
0.629
0.681
0.556
0.258
0.374
0.118
0.144
0.128
0.154 2.147
1.203
1.173
1.154
0.862
0.819
0.762
0.501
0.465
0.413
0.315
0.177
0.154
Source: United States Department of Agriculture Nutrient Data Laboratory
Important Note: Health food stores carry multiple different types of fish oil. While no specific brand is recommended, and supplements are generally not controlled by the U.S. Food and Drug Administration (FDA), it is probable that the mid-priced, generic brands are just as good as the very expensive brands. Expect to pay $15-$30 for a month's supply. The key is to ensure that the product is mercury-free, as pure as possible and contains the right amount of EPA and DHA. The amount of EPA + DHA should add up to close to 1,000mg.
Treatment
Increasing omega-3 fatty acid intake through dietary sources is preferable in healthy people. It has never been shown in rigorous clinical trials that using over-the-counter omega-3 fatty acid supplements has the same benefits. In fact, the best clinical evidence so far shows no benefit of omega-3 fatty acid supplements.
On the other hand, for people with known coronary artery disease, one clinical trial from 1999 showed that 1 gram per day of fish oil supplement improves outcomes. Also in people with heart failure (particularly with reduced heart pump function, ejection fraction [EF] less than 40 percent), the same dose of omega-3 fatty acid supplements may improve outcomes. Based on this, the recommended dose for people with documented heart disease has been at least 1 gram per day of EPA + DHA. Since then, many large, randomized trials have shown no consistent benefit of omega-3 fatty acid supplements in populations at high risk for coronary heart disease. However, treatment with omega-3 fatty acid supplements is still considered reasonable for people with known coronary artery disease and congestive heart failure with reduced ejection fraction. Even a potential modest improvement in outcomes would justify its use, as it is without concerning side effects. This amount of omega-3 fatty acids (1 gram per day) would require considerable fish consumption, to the extent that it is impractical for most. As such, fish oil supplements, either over-the-counter or pharmaceutical grade, are typically used to achieve recommended levels. This is often the case for people with high triglycerides, which may require high levels of omega-3 fatty acid intake. People taking more than 3 grams per day of omega-3 fatty acids from capsules should do so only under a doctor’s care. At these doses, omega-3 fatty acid supplements can increase the risk of bleeding in some people.
Population Recommendation Patients without documented coronary heart disease (CHD) Eat a variety of (preferably fatty) fish at least twice a week. Include oils and foods rich in ALA (flaxseed, canola, and soybean oils; flaxseed and walnuts) Patients with documented CHD Consume about 1g of EPA+DHA per day, preferably from fatty fish. EPA+DHA in capsule form could be considered in consultation with a physician. Patients who need to lower triglycerides 2 to 4 grams of EPA+DHA per day provided as capsules under a physician's care.
Source: American Heart Association
Side Effects of Omega-3 Fatty Acids
Omega-3 fatty acids are essentially free of side effects at generally recommended doses (1 to 4 grams per day). Although rare, side effects generally consist of a fishy aftertaste and/or gastrointestinal upset. These side effects can be decreased by freezing the capsules or taking the supplements at night.
Predatory fish, such as sharks, swordfish, tilefish and mackerel, contain higher levels of mercury. Therefore, the benefits and risks of eating fish vary depending on a person’s stage of life. Children and pregnant women are advised by the U.S. Food and Drug Administration (FDA) to avoid eating those fish with the potential for the highest level of mercury contamination. For middle-aged and older men and postmenopausal women, the benefits of fish consumption likely outweigh the potential risks when the amount of fish eaten is within the recommendations established by the FDA and Environmental Protection Agency. Fish oil contains only small levels of mercury and is felt to be free of mercury-related toxicities.
Theoretical concerns of increased bleeding have been largely dismissed due to a number of clinical studies. These studies failed to demonstrate any change in bleeding. High doses of omega-3 fatty acids (more than 3 grams per day) have been associated with a slight rise in bad cholesterol (low density lipoprotein, or LDL) and blood sugar.
Goals of Taking Fish Oil Supplements
In the highest risk people, improving cholesterol levels is critical to achieving clinical success. The goal should be LDL of less than 70; HDL greater than 40-45 and triglycerides under 150 mg/dL. Extensive lifestyle modification is also important. Talk to your doctor today about including fish oil and other beneficial changes into your life to prevent heart disease.
Studies on Omega-3s
Recent data suggest that there may not be as much of a benefit for taking fish oil regularly.
A 2008 meta-analysis published in the Canadian Medical Association Journal (CMAJ. 2008;178(2):157-64.) showed that fish oil supplementation did not give a preventive benefit to cardiac patients with ventricular arrhythmias.
A more recent 2012 meta-analysis published in the Journal of the American Medical Association (JAMA 2012; 308 (10): 1024–33.) found that supplementation did not reduce the chances of death, cardiac death, heart attack or stroke. As such, many providers are no longer recommend fish oil preventively.
Fish oil has demonstrated benefit in the treatment of hypertriglyceridemia, but may also increase LDL (bad cholesterol) in larger doses.
The first large scale randomized controlled trial of omega-3 fatty acids in a usual risk patient population for primary prevention was the VITAL trial reported in the New England Journal of Medicine (N Engl J Med 2019;380:23-32.). The results of this trial indicate that supplementation with omega–3 fatty acids at a dose of 1 gram per day was not effective for overall primary prevention of heart disease among healthy middle-aged men and women over five years of follow-up. This is one of the largest trials on this topic.
The GISSI-HF Trial (Lancet. 2008; 372(9645):1223-30.) showed that omega-3 fatty acid supplementation is a simple and safe treatment for patients with heart failure and can improve outcomes when used in addition to usual care.
The GISSI-Prevenzione Trial (Lancet. 1999; 354(9177):447-55.) showed that omega-3 fatty acid supplementation can improve outcomes in patients with recent heart attack.
U.S. adults are not meeting recommended levels for fish and omega-3 fatty acid intake: results of an analysis using observational data from NHANES 2003–2008 - Nutrition Journal
In general, the present NHANES analysis demonstrates that a large percentage of the US adult population is not meeting recommendations for omega-3 fatty acid consumption set forth by the 2010 DGA. Intakes of fish high in omega-3 fatty acids EPA and DHA, were greater in older adults and in males in comparison to younger adults and females, respectively.
Heart disease is the leading cause of death for both men and women in the US [1]. The 2010 Report of the Dietary Guidelines Advisory Committee (DGAC) on the Dietary Guidelines for Americans acknowledged that Americans adults consume too little seafood and should be encouraged to increase consumption to leverage heart health benefits [19]. The DGAC cited previously published literature that demonstrated biological effects of EPA and DHA. Specifically, EPA and DHA supplementation as a treatment strategy lowered blood concentration of triacylglycerol as a marker of CVD, lowered overall mortality in persons with CVD, and lowered arrhythmias and sudden death [19, 20]. This prompted the 2010 DGA to recommend 8 oz of seafood per week to contribute an average of 250 mg per day of long-chain omega-3 fatty acids, for all Americans. Furthermore, 2010 DGA [5] cited the importance of ensuring maternal dietary intake of long chain omega-3 fatty acids, in particular DHA, during pregnancy and lactation. The American Heart Association’s recommendation is to consume at least two 3.5 oz fish meals per week to reduce the risk of CVD, with an emphasis on fatty fish salmon, herring, mackerel, sardines) to increase EPA and DHA [6]. A total of 1 gram per day of EPA plus DHA from a combination of higher omega-3 fatty acid- containing fish and supplements, if needed, in individuals with established CVD [3, 5, 6].
Fish is not a habitually consumed food in the US, creating a challenge in estimating usual intake [7]. In the US, per capita salmon consumption represents the single largest contributor to dietary intake of long-chain omega-3 fatty acids [21]. Previous findings report intake of total omega-3 fatty acids in the United States to be approximately 1.6 g/day, of which 0.1-0.2 g/day stemming from EPA and DHA and 1.4 g/day from ALA [22]. Our current data show that US adults ≥ 19 years of age consume 0.41 g/day and 0.72 g/day of EPA and DHA from foods and supplements, respectively. While daily intake has increased substantially in nearly two decades, American adults are not meeting recommendations for fish-derived omega-3 fatty acids. Interestingly, our study showed comparable ALA intake to the earlier study [22], suggesting that plant-based omega-3 fatty acids may not have the consumer awareness when it pertains to heart health benefits.
Both recent and previously published literature, including evidence from randomized controlled trials, have documented the cardiovascular benefits linked to dietary omega-3 fatty acid consumption in CVD patients as well as healthy individuals [3, 7, 23–25]. While CVD is a leading cause of death in Americans, the disease rarely manifests in childhood or adolescence [26], however, the process begins in childhood and can be highly reversible (see [27] for review). In contrast, compelling evidence supports that early identification of predisposing factors and lifestyle modifications can significantly reduce the incidence of clinical disease development [26]. Children do not develop atherosclerosis per se, but rather present fatty streaks that are reversible (see [27] for review). While long-chain omega-3 fatty acid consumption benefits are not well established in children, as they are in adults, preliminary evidence suggests cardiovascular benefits in children, including improved endothelial function [28] and blood pressure [29]. In fact, when considering blood pressure, researchers have suggested that elevated blood pressure in adulthood may be associated with perinatal omega-3 fatty acid deficiency [29]. Again, such studies suggest that early exposure to dietary long-chain omega-3 are play a critical role in supporting heart health and reducing CVD risk in later life.
A limitation of this report is that the estimates relied on self-reported dietary data for intake of total fish and omega-3 fatty acids from both foods and dietary supplements. The models that we applied also relied on assumptions that reported nutrient intakes from food sources on 24-h recalls were unbiased, and the self-reported dietary supplement intake reflected the true long-term supplement intake. The data presented in the manuscript should also be interpreted ones that provide associations and not cause and effect due to the observational nature of the analysis.
