Fish Oil

The Best Source and Optimal Dosing of this Anti-inflammatory Nutrient

By Douglas MacKay, ND

When recommending fish oil to my geriatric and baby boomer patients the most common response I get is, "My grandmother used to make me take cod liver oil from a spoon." As it turns out, grandma was right.
Because of their health-promoting abilities, omega-3 fatty acids have received recognition from some of the top medical organizations in the world including, the American Heart Association, American Diabetes Association, World Health Organization, United Kingdom Scientific Advisory Committee on Nutrition, European Society for Cardiology, and The British Nutrition Foundation.
Fish Oil and Health
The health benefits of fish oil boil down to a few simple concepts.
First and foremost, EPA and DHA are absolutely essential for proper cellular health. EPA and DHA are required constituents of ALL cell membranes from our head to our toes and inside out. As constituents of cell membranes EPA and DHA are determinants of cell receptor action, hormone binding, cell fluidity, signal transduction, ion channel function, and membrane-bound enzyme activity.1
Let’s pause for a second to ponder the significance of these actions.
There are literally thousands of prescription drugs designed to modify one or more of the cellular functions mentioned above. In regards to fish oil, we are talking about one single non-toxic health promoting substance that can influence ALL of these actions.
The second major benefit of EPA and DHA is related to their function as precursors to eicosanoids. In my years of providing technical support for nutritional supplement companies and talking with doctors about eicosanoid production I have come to the conclusion that few doctors really appreciate the power and complexity of the eicosanoid cascade.
Eicosanoids are short lived, potent, hormone-like molecules that act as messengers and mediators of the immune/inflammatory response. There is a wide variety of eicosanoids produced during an immune response each with a different action and intensity.
Every cell in the body is surrounded by a cell membrane, which consists of a lipid bilayer and embedded proteins and glycoproteins. The lipid bilayer is made-up of individual fatty acids arranged in such a manner to create a semi-permeable barrier that protects a cell from its surroundings. Fatty acids within the cell membrane not only provide a protective envelope, but also serve as a reservoir of individual fatty acids for making eicosanoids.
When the immune system is triggered into action, phospholipase A2 releases individual fatty acids from the cell membrane. While in the extra-cellular space these fatty acids are taken up by enzymes such as cyclooxygenase (COX) and lipoxygenase (LOX) and converted into eicosanoids.
The predominant fatty acids consumed via the Standard American Diet are the omega-6 linoleic acid and arachidonic acid. Americans consume excess linoleic acid by eating a variety of vegetable oils including corn, soy, safflower, and sunflower that are ubiquitous in our food supply. Arachidonic acid comes mainly from animal products such as meat and eggs.
All dietary fatty acids, including omega-3 and omega-6 fatty acids, are incorporated into cell membranes. When the immune system is stimulated by allergens, injury, or infection fatty acids are released from cell membranes. Omega-6 fatty acids are converted into eicosanoids by the same enzymes (COX and LOX) that act on omega-3 fatty acids. Omega-6 and omega-3 fatty acids are actually in competition for binding sites on the COX and LOX enzymes. The critical difference is that the corresponding eicosanoids synthesized from omega-6 fatty acids drive a very aggressive and potent inflammatory response.
On the flip side when omega-3 fatty acids are converted into corresponding eicosanoids, these eicosanoids direct an anti-inflammatory response. Studies have shown that EPA blocks the release of arachidonic acid from cell membranes and reduces the production of prostaglandin E2, a very potent inflammatory and platelet aggregatory eicosanoid.2
The relative amount of omega-6 to omega-3 fatty acids found within cell membranes will determine the body’s inflammatory status. Excess omega-6 consumption results in a high omega-6:omega-3 ratio in cell membranes. When the immune system is challenged by allergy or infection, predominantly omega-6 eicosanoids are formed. This results in an aggressive and sustained inflammatory response. When optimal omega-6:omega-3 ratio (2:1) is maintained, a balanced immune/inflammatory response occurs.
In my years of following fish oil research I have often wondered why only EPA gets recognition for having anti-inflammatory activity. What about DHA? EPA and DHA are molecularly similar. They both reside in the cell membrane, and both are released from the cell membrane by phospholipase A2. I have always been suspicious that DHA may play a role in the inflammatory/immune response as well.
Conventional wisdom up to this point has told us that DHA functions only as a structural component of cell membranes. It helps with cell membrane fluidity and signal transduction. DHA has a clinical reputation for treating conditions involving the eyes, brain, and nervous system where DHA is found in higher concentrations within those cell membranes.
My intuition was correct. Recently researchers have discovered that DHA is also a substrate for COX-2. A newer class of compounds, known as resolvins, docosatrienes, and neuroprotectins has been identified in healing inflammatory tissue. It has been determined that these compounds are generated from EPA and DHA and posses anti-inflammatory, protective, and immunoregulatory properties.3 As more data becomes available we may discover that DHA is a partner to EPA in dampening inflammation and neutrophil mediated injury.4
Proper Dosage
When speaking to doctors about the benefits of omega-3 fatty acids the most common question I receive is, “What is the dose?” In my earlier days I would comb through Medline and investigate published studies, looking for information on the particular condition in question, and try to figure out the correct dose.
Anyone who has tried these same steps knows the number of published articles pertaining to fish oil is currently in the thousands with a wide range of doses being investigated. To add to the confusion institutions such as the American Heart Association heed caution with doses higher than three grams per day while influential physicians such as Barry Sears recommend mega-doses in the 10 gram and higher range.
A further complication to the dosing question is that not all fish oil provides the same amount of EPA and DHA. There is cod liver oil, fish body oil, and fish oil concentrates with a broad range of EPA and DHA. Some doctors recommend fish oil in grams and forget to specify if they are referring to grams of total oil or grams of elemental EPA + DHA (total milligrams of EPA and DHA combined). As you can see the dosing question is as murky as the ocean waters.
Recently, I was lucky enough to hear a presentation by Dr. Alex Richardson who shed some light into these murky waters. In her presentation Dr. Richardson made a profound, yet simple, correlation between the optimal dose of omega-3 and its direct correlation to the background intake of omega-6. It finally all made sense to me—clinical benefits, cell membrane function, and the inflammation/immune connection are all based on getting the correct balance of omega-6:omega-3 within the cell membrane.
We need omega-6 fatty acids. In and of themselves, they are not villains. The key is in the relative amounts of omega-6:omega-3. We have all heard how the Paleolithic diet was closer to a 2:1 omega-6:omega-3 ratio while our modern diet is closer to a 20:1. The high omega-6 ratio drives excess inflammation, which is possibly the single biggest underlying cause of chronic diseases such as heart disease, diabetes, metabolic syndrome, autoimmune diseases, and cancer.
As physicians we discuss the notion of “balancing our fatty acid intake” but Dr. Richardson took it one step further. She did a thorough analysis of the amount of omega-6 fatty acids consumed by different cultures throughout the world and estimates the amount of omega-3 fatty acids necessary to achieve a target ratio of omega-6:omega-3 (approximately 2.5:1 omega-6:omega-3). Amongst the cultures she analyzed she found the intake of omega-3 fatty acids necessary to achieve a protective tissue level varied more than 10-fold. (Figure 1)

This information has helped to shape my dosing recommendations tremendously. In patients that I would like to mega-dose for any significant period of time I prefer to start with a blood spot fatty acid analysis to objectively determine the amount of omega-3 necessary to achieve tissue balance.
In patients that I do not blood spot test, I use Dr. Richardson’s estimates. Based on the average consumption of omega-6 oils in the American diet, she has shown that it takes approximately 2 grams of elemental EPA + DHA daily to achieve a protective balance.
Remember, a 2-gram per day recommendation does not simply mean take two 1,000 mg capsules. We are talking about 2 grams of elemental EPA + DHA, which can range from around 3 to 9 capsules depending on the concentration of EPA and DHA in the capsule. (Figure 2)

In my practice the most common fish oil recommendation I make is Nordic Naturals EPA Capsules, 4 per day, with a simultaneous reduction of dietary soy, corn, safflower, and sunflower oils.
Rancid Fish Oil: More Harm Than Good?
Recently I was taking the history of a new patient who is a pharmacist. When reviewing his supplements, I learned that he was taking a commodity grade fish oil purchased at a discount grocery store. I encouraged him to do a taste test and chew a Nordic Naturals EPA capsule, then chew one of his commodity grade capsules.
To no great surprise the EPA Capsules tasted great and the commodity oil had the characteristic rank taste and smell of a bad fish oil product. The surprise was that the pharmacist’s response was, “This fish oil is very inexpensive and fish oil is fish oil—right?” My response: “WRONG!”
Any oil exposed to light, heat, or oxygen is subject to free radical attack and oxidative damage. Fish oil is made up of many long chain polyunsaturated fatty acids (PUFAs), which have many double bonds in the chain. Everywhere there is a double bond there is good opportunity for free radical attack.
Recently researchers have discovered that free radical catalyzed peroxidation of omega-3 fatty acids leads to the formation of a family of compounds that may be harmful to the body. For instance, free radical damage to DHA leads to the formation of neuroprostanes. Neuro¬ prostanes are currently being investigated as markers for oxidative stress in the brain that may contribute to neurodegenerative diseases such as Alzheimer’s and Parkinson’s.5 Rancid oil will simply add to the body’s oxidative stress load and expose it to molecules such as neuroprostanes.
The best fish oil manufacturers test their oil for freshness by analyzing it for peroxide value, anisidine value, and totox value. These measurements give a good indication of how much free radical damage has occurred in the oil. In addition, if fish oil smells or tastes rank, it should be thrown out.
Omega-3 Fatty Acids: The Best Sources
Fish oil is unequivocally the best source for omega-3 fatty acids. Some purists still recommend eating fish to achieve optimal omega-3 levels. Unfortunately contamination of our oceans has made reaching optimal omega-3 levels via eating fish a potential health hazard. Both the Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA) have sounded the alarm regarding the potential dangers of consuming too-much fish because of the associated toxins.6 In addition, studies have compared levels of mercury and organochlorines in fish versus fish oil supplements and concluded fish oil provide the benefits of omega-3 fatty acids without the risk of toxicity.7-8
Because there are no fish oil quality standards in the United States, individuals must determine what standards a manufacturer is voluntarily following—if any—to ensure the fish oil is without contamination. The highest standards in the industry today are the Norwegian Medicinal Standard (NMS) and the European Pharmacopoeia Standard (EPS). By following these standards a manufacturer can guarantee quality products by setting maximum allowances on peroxides, heavy metals, dioxins, furans, and PCBs.
During new patient visits I am dismayed to find patients still take flax oil as a source of essential omega-3 fatty acids. Flax and flax oil can be a part of a healthy diet, but it is not an adequate source of the omega-3 fatty acids EPA and DHA.
Flax oil is an excellent source of the long chain omega-3 fatty acid known as alpha-linolenic acid (ALA). This 18-carbon fatty acid is a precursor to EPA (a 20 carbon omega-3 fatty acid) and DHA (a 22-carbon omega-3 fatty acid). ALA is not associated with the many health benefits attributed to EPA and DHA. To get EPA and DHA from consuming ALA requires several metabolic steps (elongation and desaturation) that are governed by two important enzymes known as delta-6 desaturase (D6D) and delta-5 desaturase (D5D).
Metabolic studies have shown that the enzymatic activity of D6D and D5D are impaired by intake of saturated and trans fatty acids, alcohol, stress-hormones, smoking, viral infections, ionizing radiation, and aging. It is hard to find a patient without these obstacles to converting ALA to EPA and/or DHA.
In general, the exact rate of conversion of ALA to EPA and DHA is a matter of debate. A thorough review of the literature reveals a range of estimated conversions of ALA to EPA with a maximum being around 15 percent and a minimum of 2-3 percent. The estimates are even less promising for conversion to DHA.
Therefore, in conditions that have been shown to be supported by EPA and/or DHA, pre-formed EPA and DHA from fish oil is the most effective means to nourish the body with these essential fatty acids.
Why I Use Nordic Naturals Fish Oils
In my practice I use Nordic Naturals exclusively for several reasons. All of Nordic Naturals products taste great. Taste is directly correlated to freshness and lack of oxidative damage to the oil. Using great tasting fish oil that does not repeat on my patients results in good patient compliance leading to clinical results.
Nordic Naturals takes several steps during the manufacturing process to eliminate free radical damage. The owners of Nordic Naturals are Norwegian and have developed relationships with independent fishermen that use smaller boats rather than larger trawling vessels that spend a longer time at sea. This means there is less time between the catch and the initiation of the oil extraction, which is done in a low heat, nitrogen-rich environment. Third party analysis of Nordic Naturals oils has resulted in anisidine values between 1 and 2, five to 10 times below the industry average.
Nordic Naturals also adheres to Norwegian Medicinal Standard (NMS) and the European Pharmacopoeia Standard (EPS) and consistently are well below allowable amounts of peroxides, heavy metals, dioxins, furans, and PCBs. Another reassuring fact is that leading research institutions around the world choose Nordic Naturals oils for their clinical trials.
Douglas MacKay, ND is a licensed Naturopathic Doctor who is committed to the advancement of natural and preventive medicine. A national lecturer, Dr. MacKay divides his time between practice, research and advocacy, and has had several articles published in peer review medical journals. Dr. MacKay has served as medical consultant and technical advisor to the nutritional industry for the past seven years. He also has a thriving family practice in the New Hampshire Seacoast area. The Makai Naturopathic Center, located in Dover, N.H., combines Naturopathic, Chiropractic and Chinese Medicine under one roof for a new standard in family medicine.
References
1. Lerman R. Essential Fatty Acids. Integrative Medicine. 2006;5:34-44.
2. James MJ, Gibson RA, Cleland LG. Dietary polyunsaturated fatty acids and inflammatory mediator production. Am J Clin Nutr. 2000;71(1 Suppl):343S-348S.
3. Serhan CN, et al. Resolvins, docosatrienes, and neuroprotectins, novel omega-3 derived mediators, and their aspirin-triggered endogenous epimers:an overview of their protective roles in catabasis. Prostaglandins Other Lipid Mediat. 2004;73:155-172.
4. Serhan CN. Novel omega-3-derived local mediators in anti-inflammation and resolution. Pharmacol Ther. 2005;105:7-21.
5. Montine KS, Quinn JF, Zhang J, et al. Isoprostanes and related products of lipid peroxidation in neurodegenerative diseases. Chem Phys Lipids. 2004;128:117-124.
6. U.S. Environmental Protection Agency WEBSITE: http://www.epa.gov/waterscience/fishadvice/advice.html
7. Melanson SF, et al. Measurement of organochlorines in commercial over-the-counter fish oil preparations: implications for dietary and therapeutic recommendations for omega-3 fatty acids and a review of the literature. Arch Pathol Lab Med. 2005;129:74-77.
8. Foran SE, et al. Measurement of mercury levels in concentrated over-the-counter fish oil preparations: is fish oil healthier than fish? Arch Pathol Lab Med. 2003;127:1603-1605.