Omega-3 Fatty Acids: Agents of Resolution

Omega-3 Fatty Acids: Agents of Resolution
The Zone Diet is the foundation of the Zone Pro-Resolution Nutrition system for optimizing the Resolution Response because it reduces diet-inflammation that otherwise amplifies existing chronic unresolved cellular inflammation. That amplification factor can overwhelm the natural mechanisms of resolution and repair that are needed to lead to complete healing of any injury. To use an analogy, consider diet-induced inflammation like a burning house. First you must reduce the intensity of the existing fire before you can completely extinguish it, and only then can you begin to repair the damage.

In other words, the Zone Diet reduces the intensity of inflammatory fire, but it will not completely put it out. For that critical task you need high-dose omega-3 fatty acids to increase the generation of resolvins needed to resolve the remaining residual cellular inflammation in order to complete the Resolution Response by activating AMP kinase with adequate levels of polyphenols to repair the damage.

Eicosanoids Versus Resolvins
Eicosanoids are hormones derived from arachidonic acid (AA), which is an omega-6 fatty acid that turns on and determines the intensity of the inflammatory response. The vast majority of eicosanoids are pro-inflammatory, although there are a few that have anti-inflammatory properties as described in Appendix D. Technically, turning on inflammation is known as initiation. The higher the levels of eicosanoids in your body, the greater the intensity of cellular inflammation. The Zone Diet does an excellent job of reducing the formation of AA, thus lowering the levels of the eicosanoids that can amplify the intensity of cellular inflammation without compromising your initial inflammatory response to any injury (external or internal). Therefore, you can consider the Zone Diet to be an anti-inflammatory diet.

On the other hand, the long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the molecular building blocks for the generation of resolvins necessary to turn off the inflammation response. Technically, this turning off of the inflammation process is known as resolution. Without adequate levels of EPA and DHA in your body, your body can’t resolve the remaining residual cellular inflammation caused by some injury that has been amplified by diet-induced inflammation. This is why you need omega-3 fatty acids work in tandem with the Zone Diet because the initiation of inflammation must be in a constant working balance with its resolution if your goal is to reach the Zone and optimize the Resolution Response.

The vast majority of your omega-3 and omega-6 fatty acids in your diet consist of the shorter-chain omega-6 fatty acids (such as linoleic acid) or omega-3 fatty acids (such as alpha-linolenic acid). These fatty acids must be further metabolized into their longer-chain cousins that are the true building blocks for the eventual generation of both eicosanoids and resolvins. The metabolic pathways that lead to eicosanoids and resolvins are tedious and complex, and that is why I put them in Appendix D. However, here are key points to remember.

First, the enzymes in those metabolic pathways are the same for each group of essential fatty acids. This means if you have an excess of short-chain omega-6 fatty acids (like linoleic acid) in your diet, they will inhibit the further metabolism of short-chain omega-3 fatty acids into EPA and DHA. As a result, this means you will potentially generate many more eicosanoids and fewer resolvins. This alone virtually ensures you will be in a constant state of cellular inflammation.

Second, the activity of the key enzymes that are the “gate-keepers” for the generation of AA generation are controlled by the balance of the hormones (insulin and glucagon) generated by the Zone Diet. Insulin speeds up their activity, and glucagon inhibits their activity. This is why the balance of these two hormones controlled by the Zone Diet is key for reducing cellular inflammation. It is the balance of carbohydrates (that stimulate insulin) and protein (that stimulate glucagon) at every meal that determines the rate that AA is formed. Furthermore, if you develop insulin resistance (a predictable consequence of increased cellular inflammation), then your insulin levels are always elevated. If you are consuming a lot of omega-6 fatty acids as most Americans do primarily via vegetable-based cooking oils, then you are virtually guaranteed you will be making excessive levels of AA that generate increased levels of eicosanoids and maintain you in a state of constant cellular inflammation. This is shown below.

Once I understood the importance of maintaining the dynamic balance of insulin and glucagon to ultimately control the levels of AA, it became the driving force for developing the Zone Diet. The Zone Diet provided me the dietary tool I needed to reduce the intensity of diet-induced inflammation. In essence, the Zone Diet became the traffic cop critical for controlling the balance of hormones (insulin and glucagon) generated at each meal to decrease the production of AA that can ultimately increase cellular inflammation that in turn damages our organs.

However, when I wrote The Zone, virtually nothing was known about the resolution of inflammation. It was only later when I become aware of the importance of high-dose omega-3 fatty acids to turn off or resolve inflammation, did I realize that using high-dose omega-3 fatty acids would be critical. That’s why my book The OmegaRx Zone was subtitled The Miracle of High-Dose Fish Oil.

Resolvins derived from omega-3 fatty acids represent a broad class of newly discovered hormones that include resolvins, protectins, maresins, and others. These hormones are derived from long-chain omega-3 fatty acids such as EPA and DHA and are essential to resolve the inflammatory process. But how much supplementation of omega-3 fatty acids will you need to generate an adequate resolution of residual cellular inflammation? That can be determined by the AA/EPA ratio in your blood that I discussed earlier as one of the three clinical markers that defines the Zone.

Resolvin Pathways
Our current knowledge of the molecular pathways leading to resolution can easily be traced to one person—Charlie Serhan at Harvard Medical School. Charlie started his research career in inflammation the same time that I became interested in eicosanoids. Charlie realized that while eicosanoids turned on inflammation, something had to turn it off. That led to his more than thirty-year journey into the mysterious world of resolvins. It has been Charlie’s leadership in the discovery, synthesis, detection, and use of resolvins for disease treatment that has almost single-handedly driven this entire field.

I use the term “resolvins” to broadly describe the vast array of newly discovered hormones involved in resolution. Technically these hormones are known as specialized pro-resolving mediators (SPM). Frankly, that’s a mouthful, so I simply lump them all together as resolvins to keep your focus on the resolution of cellular inflammation. Optimal resolution requires that adequate levels of both EPA and DHA be maintained as a reservoir in the body since resolvins are made on demand. Furthermore, you need adequate levels of both EPA and DHA because each omega-3 fatty acid generates different types of resolvins that have unique functions in the resolution process.

A brief overview of the different classes of resolvins that can be generated is shown below and is explained in more detail in Appendix D. 

How Much EPA and DHA Do You Need?
Reaching an optimal AA/EPA ratio between 1.5 and 3 that is required for the resolution of residual cellular inflammation will usually require supplementation with highly purified omega-3 fatty concentrates for most individuals. How much supplementation depends on your current state of health as shown in the following chart.

Health ConditionGrams of EPA and DHA needed per dayCategory of Supplementation
Currently Well2.5Minimum Dose
Obesity, Diabetes, or Heart Disease5Moderate Dose
Chronic Pain7.5High-Dose
Neurological DiseaseGreater than 10Very-high Dose

To put these suggested levels of daily intake of EPA and DHA in perspective, the average American consumes about 150 mg (0.15 g) of EPA and DHA per day. That’s why their AA/EPA ratio is about 20. The more you reduce AA by following the Zone Diet, the less supplementation with omega-3 fatty acids you will require to reach the ideal AA/EPA ratio necessary to enhance the resolution of residual cellular inflammation.

Let’s look into that table with a little more detail. I consider 2.5 grams of EPA and DHA to be a minimum daily intake of omega-3 fatty acids. This is about the amount of EPA and DHA found in a tablespoon of cod liver oil–something that nearly every child took before leaving the house in the first half of the 20th century. You can quickly calculate that the current American intake of 150 mg of EPA and DHA per day represents a 95 percent reduction in my recommended minimum dose needed for the resolution of cellular inflammation.

OK, maybe you are not so healthy. Maybe you are obese (as defined by percent body fat, not BMI), have a high AA/EPA ratio (like most Americans), have a chronic disease like diabetes or heart disease, or have severe insulin resistance. You are definitely more inflamed. Now you will need about 5 grams of omega-3 fatty acids per day to bring your AA/EPA ratio into its appropriate range for resolution of unresolved cellular inflammation.

But what if your inflammation is no longer silent as might be the case in individuals with rheumatoid arthritis and other auto-immune conditions or those with cancer pain? Then you would need to take a higher dose of about 7.5 grams of omega-3 fatty acids per day. This is also true for elite athletes who live in a world of constant inflammation caused by the intensity of their exercise. Finally, what if the cellular inflammation is concentrated in the brain like various neurological conditions such as multiple sclerosis, depression, attention deficit disorder, Parkinson’s or Alzheimer’s. Then you will likely need at least 10 grams of omega-3 fatty acids per day to reduce the AA/EPA ratio in the blood to an optimal range of 1.5 to 3. This would be considered a very high-dose, but it is also a therapeutic dose required to reduce the AA/EPA ratio for the successful management of those neurological conditions.

The primary reason that omega-3 fatty supplementation is considered controversial is because the vast majority of human studies have used such a low dose of omega-3 fatty acids that the AA/EPA ratio is rarely reduced below 3, let alone even reaching an ideal level of 1.5. This is why you routinely hear news reports that omega-3 fatty acids have no benefits. If you use a placebo dose of omega-3 fatty acids, you should expect placebo results. This has been confirmed by two recent studies published in the same issue of the New England Journal of Medicine in which a dose 0.8 grams per day of omega-3 fatty acids had no cardiovascular benefits, but a dose of 3.9 grams of omega-3 fatty acids per day had significant cardiovascular benefits.

The Fat-1 Mouse
The benefits of achieving an appropriate AA/EPA ratio in the blood can be demonstrated in the fat-1 mouse. The fat-1 mouse is a genetically engineered animal containing genes from a worm that can now allow it to make the enzymes that convert much of the omega-6 fatty acids in every organ to omega-3 fatty acids, thus maintaining their AA/EPA ratio in their blood close to 1. When you cross-bred the fat-1 mouse to other mice that are genetically predisposed to develop a wide variety of chronic diseases, you find that the cross-bred fat-1 mouse is virtually resistant to developing conditions ranging from obesity, diabetes, auto-immune conditions, and neurological conditions found in the in-breed mice. The most likely reason is because of their lower AA/EPA ratio.

Obviously genetic engineering is not the most desirable way to lower your AA/EPA ratio, but you can do it via dietary supplementation. In animal models, it usually requires 100-200 mg EPA and DHA per kilogram body weight. For a 70 kg (154 pound) individual that would be about 7 to 14 grams of EPA and DHA per day. Those are also the same levels I have used in some of my clinical studies to better manage brain trauma, macular degeneration, and type 1 diabetes that I will describe later in this chapter.

Why Not Just Eat More Fish?
Rather than taking omega-3 fatty acid supplements, why not simply eat more fish rich in omega-3 fatty acids? The Japanese are able to maintain a low AA/EPA ratio only because they are the largest consumers of fatty fish in the world. So why can’t Americans? The problem is that the most popular types of fish consumed in America are lean, and therefore low in omega-3 fatty acids. This means you can’t reach the necessary blood levels of omega-3 fatty acids you need for generating the necessary levels of resolvins required for optimal resolution of residual cellular inflammation.

Let’s assume you wanted to consume 5 grams of omega-3 fatty acids which was the amount used in the study published in the New England Journal of Medicine in 1989 to lower the levels of inflammatory proteins known as cytokines. So how much more fish would you need to eat? It depends on the fish. In the following table are commonly eaten fish and the amounts you would need to get 5 grams of EPA and DHA per day.

Fish

Grams of omega-3 fatty acids

per 3.5 oz. filet

Oz. required for 5 grams of

EPA and DHA per day

Tilapia0.075230
Grouper0.100175
Tuna, yellowfin0.15090
Cod0.20070
Swordfish0.822

Salmon,

wild chinook

1.116

OK, maybe consuming one pound (16 oz.) of wild chinook salmon every day is not that difficult (although expensive), but trying to consume 14 pounds of tilapia to get the same level of EPA and DHA is simply impossible. Furthermore, if you have a chronic disease, the levels of EPA and DHA you must consume to get your AA/EPA ratio in its optimal range may require even significantly higher levels of fish consumption.

While eating enough fish to obtain adequate levels of EPA and DHA for resolution is possible, there are other significant problems caused by consuming more fish. In particular, heavy metal and chemical toxin contamination. Larger fish such as tuna and swordfish are predators, meaning they accumulate the heavy metals (primarily mercury) found in the smaller fish they consume. The larger the predator fish the more mercury it will contain. This is why there are warnings for pregnant mothers not to eat too much tuna or swordfish during pregnancy. However, a more insidious threat is that all fish contain chemical toxins such as polychlorinated biphenyls (PCBs). These industrial chemicals once thought to be inert are now known to be neurotoxins, carcinogens, and endocrine disruptors. That’s why the worldwide production of PCBs was banned in 2001. Unfortunately, PCBs are highly persistent in the environment. In other words, they are going to be around for a long time. The higher the levels of the omega-3 fatty acids in a fish, the higher the levels of accumulated PCBs they contain since these toxins are fat-soluble and concentrate in the fat deposits of the fish.

The solution to both problems of high levels of mercury or PCBs and still getting adequate levels of EPA and DHA to promote resolution is the supplementation with ultra-refined omega-3 fatty acid concentrates.

Omega-3 Fatty Acid Purity
The unfortunate fact is that all fish are contaminated by either environmental toxins like heavy metals (like mercury coming coal burning) and industrial chemicals (like PCBs). You can run, but you can’t hide from the fact. When you purchase concentrated omega-3 fatty acids in a supplement form these problems remain. Regardless of how the omega-3 fatty acid supplements are made; their purity must be constantly tested relative to toxin levels (especially PCBs) and the rancidity of the final product.

Toxins
Although it is relatively easy to remove heavy metals such as mercury from any fish oil product, it is nearly impossible to completely remove PCBs from any omega-3 fatty acid concentrate. However, they can be reduced to exceptionally low levels using new manufacturing technologies, especially super critical fluid and low-temperature thermal purification technologies which have only recently been introduced.

Rancidity
Omega-3 fatty acids are also extremely prone to oxidation. This is why fish smells if it is not fresh. These oxidation products include aldehydes and ketones that are highly reactive chemicals that can cause damage to proteins and your DNA. You can measure the levels of these reactive chemicals using a standard test known as Total Oxidation or Totox.

Show Me the Data
Since prescription-grade omega-3 fatty acid concentrates developed in the 1990s are now generic products, their published standards by the FDA can be compared to fish oil products sold in the mass-market (health food grade) and also the newer omega-3 fatty acid concentrates (such as the ultra-refined grade) using more advanced technologies such as super-critical fluids or low-temperature thermal fractionation that are now available. The comparison of these general standards that govern oil quality is shown in Table 1.

Table 1. Purity Standards for Omega-3 Fatty Acid Concentrates

Type of oil                  Upper PCB levels (ng/g)        Upper Totox Levels (meq/kg)

Health Food grade                              90                                            26

Generic prescription

drugs                                                   50                                            26

Ultra-refined grade                             5                                              20

It can be seen from Table 1 that omega-3 fatty acid fatty acid concentrates sold by prescription are not all that different in terms of PCB purity and rancidity specifications from what is sold in a supermarket. Reducing the levels of PCBs in an omega-3 fatty acid product becomes critically important when giving high doses of omega-3 fatty acids. This is because PCB levels can build up in the blood, even when giving a prescription omega-3 fatty acid concentrate. It has been shown that if the daily intake of PCB levels increases by only 180 nanograms (0.00000018 gram) per day, that can increase the risk of cardiovascular disease by 60 percent. Those PCB levels are not very much. It is similar to adding one drop of water into the equivalent of three Olympic size swimming pools.

This is a problem in using high-dose omega-3 fatty acid concentrates to increase resolvin formation. According to the specifications in Table 1, a typical one-gram capsule of fish oil sold in the supermarket could potentially contain 90 nanograms of PCBs. Taking more than two capsules a day of such a product could increase your daily PCB intake by 180 nanograms and potentially increase the risk of heart disease. Taking four one-gram capsules of a prescription omega-3 product may possibly contain 200 nanograms of PCBs and still meet the FDA standards for a prescription drug. On the other hand, you could take 40 one-gram capsules of an ultra-refined omega-3 product before you would reach the same levels of PCB intake.

Using the new manufacturing technologies, I described above, it is now possible to produce non-prescription omega-3 fatty acid concentrates of even higher purity (approximately one nanogram of PCBs in one-gram capsule) with nearly equal omega-3 fatty acid concentrations than the current FDA specification for prescription drug omega-3 fatty acid products. This is critical for long-term, high-dose applications necessary to maintain adequate levels of omega-3 fatty acids in the blood unless you feel lucky about the purity of the fish oil you are using since PCBs are known neurotoxins, carcinogens, and endocrine disruptors. Although there are no labeling requirements for PCB levels for an omega-3 fatty acid product, a few companies will actually post such data on their websites even though I pointed out this PCB problem in my 2001 book, The OmegaRx Zone.

Rancidity
The other marker of purity are the Totox levels in the final product. Totox is the universal marker of oil rancidity. In fact, this marker is the basis for worldwide trading of all edible oils. Because of the high concentrations of omega-3 fatty acids in these concentrates (50-85 percent omega-3 fatty acids), the likelihood of developing rancidity is quite high thus the importance of adequate anti-oxidant protection to prevent rancidity. Rancidity is the result of producing chemically reactive aldehydes and ketones (the breakdown products of fatty acids during oxidation) in an omega-3 fatty acid product during its stated shelf life. The lack of sophisticated anti-oxidant systems in typical fish oil products (including prescription omega-3 drugs) is why it is likely that most fish oil concentrates can quickly develop rancidity during shipping or while sitting on the store shelf. This is because the additional refining necessary to achieve higher EPA and DHA concentrations strips out the natural anti-oxidants in the fish oil that protect the omega-3 fatty acids from oxidation. Adding back relatively weak standard anti-oxidants will not be sufficient to protect the higher concentrations of EPA and DHA from oxidizing in the bottle.

The best way to overcome this oxidation problem is to develop far more sophisticated anti-oxidant systems for use in the omega-3 fatty acid concentrates to retard rancidity development. Over the years, I have developed such anti-oxidant systems that when coupled with low levels of PCBs in the finished product makes the long-term use of high-dose omega-3 fatty acid supplements to resolve residual cellular inflammation a reality.

Of course, the simplest way to test for rancidity may be simply to bite into the fish oil capsule and taste the oil.   If it is bitter, it’s rancid and will probably do more harm than good for you since you are tasting the aldehydes and ketones. Most omega-3 concentrates simply don’t pass the taste test. Some health food grade products will try to bypass this problem by adding flavors (lemon being the most common) to mask the taste. These products will not taste bitter even though the resulting Totox values of such flavored products are often well above the standard that defines rancidity.

History of Omega-3 Fatty Acid Concentrates
The history of using fish concentrates started more than 2,000 years ago with the use of garum consisting of fermented fish intestines that were prized as a seasoning in ancient Roman times. Large garum factories were located throughout the Roman Empire as garum was considered far more valuable for health than olive oil. Unfortunately, with the fall of the Roman Empire, the recipe for garum was also lost.

The next major advance in fish oil supplementation occurred in the 1780s when the first cod livers from America were sent back to England where they were fermented (by rotting) in wooden vats. The oil released from the fermenting cod livers rose to the top of the vats and was considered a miracle treatment for rheumatoid arthritis. The fermented cod liver oil contained about fifteen percent by weight of omega-3 fatty acids. In the 1850s, Norwegians started heating the cod livers in iron kettles rather than letting them rot in wooden barrels like the British. This greatly accelerated the extraction of the cod liver oil with a slightly better taste. This was the technique used for most fish oil production in the 20th century.

In the 1980s, the use of fish body oils began to replace cod liver oil for two reasons. One benefit was to nearly double the omega-3 fatty acid content to approximately thirty percent of the total fatty acids, and second, there was a dramatic reduction of Vitamin A levels compared to cod liver oil, thus reducing the potential of Vitamin A toxicity that could result in an increase of calcium levels in the blood.

In the late 1990s, manufacturing technology began using molecular distillation enabling the production of even higher concentrations of omega-3 fatty acids. This is the methodology used to make current prescription drugs containing omega-3 fatty acids. However, this older technology has been dramatically improved with the introduction of either super critical fluid extraction or low temperature thermal fractionation techniques to obtain even higher purity omega-3 fatty acid concentrates with far better taste and purity characteristics thought possible using molecular distillation alone that I have described earlier. When you supplement with high purity omega-3 fatty acid concentrates at therapeutic levels to resolve residual cellular inflammation, the results can be extraordinary.

Treating “Untreatable” Conditions with High-Dose Omega-3 Concentrates
The powerful benefits of high-dose omega-3 concentrates have been demonstrated in the treatment of conditions for which there is no known drug therapy. Such untreatable conditions fall into three major categories; severe brain trauma, age-related macular degeneration (AMD) and optical nerve damage, and the treatment of type 1 diabetes.

Raising the Dead: Treating Severe Brain Damage
In 2006, a major disaster occurred in West Virginia at the Sago mine. Thirteen miners were trapped in a carbon monoxide-rich atmosphere for more than 41 hours. No human being has ever survived such a prolonged period of carbon monoxide exposure. When the rescue team finally reached the trapped miners, twelve of the thirteen were dead. The one remaining survivor was as close to death as medically possible. He had heart failure, kidney failure, and liver failure. When they examined his brain by MRI, most of his myelin (i.e. white matter) was destroyed by inflammation induced by the carbon monoxide poisoning. That evening I received a phone call from the head physician of the Level 1 Trauma Center in West Virginia where the lone survivor (Randall McCoy) had been sent for treatment. That physician was Julian Bailes who is one of the top neurosurgeons in America. The reason Julian called me was to see if high-dose fish oil might keep Randall alive because he had read my book The OmegaRx Zone several years earlier. I agreed and suggested giving the miner 15 grams of EPA and DHA per day. After a long pause over the phone, Julian countered that his patient would probably bleed to death with such high levels. I assured him that wouldn’t happen because there was a blood test to make sure that we could adjust the dose of omega-3 fatty acids, so the AA/EPA ratio would never drop below 1.5. Julian agreed, since he had no other options. That night I air-shipped several bottles of our omega-3 fatty acid concentrates to Julian, and the next day they started giving Randall 15 grams of omega-3 fatty acids per day through his feeding tube. Eight weeks later, Randall came out of his coma and was transferred to a rehab hospital where he continued the same daily dose of omega-3 fatty acids using a tablespoon to deliver the omega-3 concentrate for another eight weeks. Four months after the mine disaster, Randall went home. His heart was normal, his kidney was normal, his liver was normal, and he gave a press conference worthy of any politician. The press touted it as a miracle. Maybe it was, and perhaps Julian and I just got lucky. But I have consistently had similar results using the same aggressive use of ultra-refined high-dose omega-3 fatty acid concentrates in a number of patients with a wide variety of severe brain trauma subtypes over the years.

One recent case study involved a young adult who had a drug overdose and choked on his vomit causing hypoxia (lack of oxygen) to the brain requiring him to be placed onto a ventilator to survive. Two months later, the physician told the parents that they should pull the plug since it was unlikely their son would ever recover. That night I got a call from the parents. I told them that I wish they had contacted me earlier, but nonetheless I shipped out an even more highly purified omega-3 concentrate that I had recently developed and an appropriate blood test kit to test his AA/EPA ratio levels. He started to improve after a few weeks, and within a few months they took him completely off his ventilator. Some 14 months after he had started with the EPA and DHA supplementation, they sent me photographs of him canoeing with his father. Four months later, I received another picture of him at his sister’s wedding. Not a bad outcome for a young man whose parents were told to pull the plug a year and half earlier. Every case is different, but supplementation with purified high-dose omega-3 fatty acid concentrates makes a lot more sense than the standard practice of putting the patient on a ventilator and hoping that time will resolve the neuroinflammation in the brain.

Curing the Blind: Restoring Sight in Macular Degeneration and Optic Nerve Damage
Ocular damage is really brain damage. One type of ocular damage is age-related macular degeneration (AMD), which is the primary cause of blindness after age 50. There are two types of AMD; dry and wet. There is no known treatment to improve dry AMD (which accounts for 90 percent of the cases) and usually most of the patients become legally blind within 10 years after developing the condition. The intervention for wet AMD (only 10 percent of AMD cases) is not to cure it, only to prevent it from getting worse with monthly injections of monoclonal antibodies directly into the eye.

Since the retina is rich in omega-3 fatty acids, it would make sense that supplementation with omega-3 fatty acids should be useful for either type of macular degeneration. Of course, that is true only if you are using therapeutic doses of EPA and DHA to reduce your AA/EPA ratio in the blood to the appropriate range. If you use placebo levels of omega-3 concentrates (like 0.8 grams of omega-3 fatty acids per day) to treat dry AMD not surprisingly you get placebo results. That’s exactly what the large-scale clinical trials confirm.

I had the opportunity to work with an ophthalmologist in Cyprus to undertake pilot studies to see if higher doses (5 to 7.5 grams of omega-3 fatty acids per day) might provide a different clinical result. That’s actually what we did for six months in his patients with dry AMD. All the patients improved. Furthermore, the clinical benefits were totally dose-dependent on the final AA/EPA ratio at six months. That is the lower the final AA/EPA ratio after six months, the greater the vision improvement for this “untreatable” condition. In those patients that reached the lowest final AA/EPA ratio (1-1.6) after six months, their vision in improved by 100 percent.

The same holds true in our unpublished observations treating optical nerve damage. It is commonly assumed that once the optical nerve is damaged, it can never repair itself. But using high-dose omega-3 concentrates (10 grams of EPA and DHA per day), dramatic vision improvements were observed after six months, even though a significant period of time (like more than a year) had passed after the optical nerve damage first occurred. During the course of the treatment, it was possible to actually observe the optical nerve regenerating as measured by the growing response to light when shined on the retina. The underlying mechanism for the regeneration of the optic nerve probably starts with the reduction of neuroinflammation similar to the repair process seen in the patients with severe brain trauma.

Treating Type 1 Diabetes
Type 1 diabetes is an auto-immune disease like rheumatoid arthritis, lupus, and multiple sclerosis. This means the body’s own immune system is attacking the target tissue.   What cause auto-immune diseases remains unknown. But of these conditions, early onset type 1 diabetes in children may be the most terrifying, because if you are a parent of a child with type 1 diabetes the data strongly suggests that if they have developed type 1 diabetes before the age of 10, their lifespan will be shortened by 14-18 years. Furthermore, there is nothing in the current medical literature that can stop its development. Maybe that can change?

Two recently published case studies from Italy suggests that using high-dose omega-3 fatty acids may be able to stop the inevitable destruction of the beta cells in the pancreas. Furthermore, it appears that regeneration of the beta cells that produce insulin may be occurring as long as the AA/EPA ratio is maintained below 3 using high-dose omega-3 concentrates.

Based on these encouraging case studies, a large-scale FDA-allowed clinical trial has begun to determine if using ultra-refined high-dose omega-3 concentrates at 7.5-10 grams of omega-3 fatty acids per day can potentially increase the body natural production of insulin in a wide variety of type 1 diabetes. If so, this may be the first real breakthrough for treating type 1 diabetics since the development of insulin injections nearly 100 years ago.

How Much Omega-3 Fatty Acids Do You Need?
A good starting dose for omega-3 fatty acids would be 2.5 grams of EPA and DHA per day whereas a good starting dose for polyphenol extracts would be 500 mg. per day. These are minimum suggested levels. The optimal level for optimal resolution of residual cellular inflammation can be determined by a simple blood test requiring only a drop of blood that was discussed in Chapter 7. In particular, the AA/EPA ratio will determine the ideal amount of omega-3 fatty acids required for resolving residual cellular inflammation.

Summary
Without adequate levels of EPA and DHA in your blood, your ability to resolve cellular inflammation will be a constant, if not difficult, struggle. Ideally, you should eat enough fatty fish to get adequate levels of both omega-3 fatty acids (as do the Japanese and especially the Okinawans). However, the contamination of fish with environmental toxins (such as mercury and PCBs) makes the use of ultra-refined omega-3 fatty acid supplements the preferred approach for significantly improving the resolution of cellular inflammation. This is one of the few times that refined is better than natural.

At moderate levels of EPA and DHA supplementation (about 5 grams of omega-3 fatty acids per day), the elevated levels of these two omega-3 fatty acids in the blood can begin to generate powerful resolvins. At still higher levels (greater than 7.5 grams of EPA and DHA per day), they become remarkable dietary complements to any drug intervention to better manage a wide variety of chronic diseases including those for which there currently is no known treatment. Regardless of the amount of EPA and DHA you are taking, make sure it is pure as well as sufficient in quantity for the resolution of residual cellular inflammation. That requires testing, not guessing.