# Arachidonic Acid?



## Great White (Apr 4, 2003)

Hello Gang

Meant to ask you lot about this a few weeks back when i got my Anabolics 2005.

There was a 12 page book in with it on Arachidonic Acid.

The 1st thing i thought of when i saw it was "Another Creatine" Loads of research and jibber jabber which leads to not much of what it claims...

Anyway, check it out for youself, X-Factor is the product that has it, im thinking of ordering a bottle just to try it out...

http://www.molecularnutrition.net/X_factor.htm

Here is what it claims to do:

*MORE PAIN, MORE GAIN*

Newly Discovered Nutrient Increases Post-Workout Soreness, and Stimulates the Core Process of Muscle Growth Itself!

Developed by performance-enhancement researcher William Llewellyn, X-Factor is turning the sports nutrition industry on its ear! This revolutionary new supplement contains arachidonic acid, the recently discovered chemical messenger that serves as the primary trigger in the anabolic (tissue-building) process. This is the compound released by your muscle fibers when you damage them during weight training, and regulates everything from androgen receptor levels, to blood flow and nutrient availability, to protein synthesis and breakdown rates, to the core process of muscle growth itself. X-Factor users notice a dramatically heightened physiological response to exercise, including greater post-workout soreness, intense pumps, rapid strength and lean body mass (LBM) gains, and noticeable fat loss. It is the first supplement designed to amplify the body's natural response to weight training, and sits in a class by itself as the most powerful non-steroidal muscle-building agent ever developed!

- Increased Protein Synthesis (Real Gains of 1-2 lbs. of Solid Muscle Per Week!)

- Increased Workout Productivity (Intensified Residual Soreness!)

- Increased Pumps (Greater Nutrient Availability to the Muscles!)

- Increased Androgen Receptors (Amplifying the Anabolic Actions of Testosterone!)

- Maximum Muscle-Mass Retention (NO Post-cycle Hormonal Crash to Rob Your Gains!)

- Significant Fat Loss (Gain Muscle AND Lose Fat at the Same Time!)

- Comfortable and Effective (No Hair loss, Libido Issues or Acne!)

*What is Arachidonic Acid? *

Arachidonic acid is an essential fatty acid, which is consumed in small amounts in our regular diets. It is found mainly in the fatty parts of meats and fish (largely in red meat). Our daily intake, even in those who eat a lot of red meat, is relatively small, owing to how little is actually found here1. For example, the visible fat area on beef only contains anywhere from 20 to 180 milligrams of arachidonic acid per 100 grams (nearly a quarter pound) of fat!2. In the lean portion of meat the arachidonic acid content is even lower. Since this particular fatty acid is so scarce, the average western diet provides only about 230 milligrams of this important nutrient to each of us per day3. The body is also adept at regulating tissue arachidonic acid levels, which means that diet alone is not enough to impart a short term anabolic effect. Once we exceed our bodies natural capacity to regulate arachidonic acid levels with the very high doses that X-Factor provides, we trigger remarkable muscle growth, strength gains, and fat loss!










Arachidonic acid is considered an "essential" fatty acid because it is an absolute requirement for the proper functioning of the human body. In this case it is vital to the operation of the prostaglandin system. More specifically, it is the base material used by the body to synthesize a key series of hormones referred to collectively as dienolic prostaglandins (the major prostaglandins in mammals4). This includes the prostaglandins PGE2 and PGF2a, which are the primary focus of our investigation. The ability of the body to output normal levels of these prostaglandins is therefore directly dependent of the availability of this fatty acid. This is of crucial importance to the athlete, because among several other important physiological roles, prostaglandins are integral to protein turnover and muscle accumulation. They operate right at the very core of muscle growth, and are responsible for regulating the direct local (muscular) response to physical exercise.

*Prostaglandins and Anabolism *

Prostaglandins begin to exert their strong effects on muscle growth immediately following physical exertion. More specifically, it is the stretch stimulus provided by eccentric muscle contraction that first triggers the local synthesis of these hormones. They in turn play a pivotal role in what will be going on in your muscles during the days of recovery that will follow. A study published in the American Journal of Physiology in 1990 perhaps looks most closely at the relationship between prostaglandins, protein turnover and the growth response to physical exercise5. In this investigation, skeletal muscle cell preparations were incubated under stretch stimulus to replicate the stimulation of exercise, and protein turnover was measured by quantifying the incorporation of the labeled amino acid phenylalanine into muscle tissue. During the first 5 hours of stimulation, PGE2 and PGF2a prostaglandin levels increased 101% and 41% respectively (PGE2 is tied to the initial damage response to exercise6). PGF2a remained elevated for 48 hours, and correlated with a 52-98% long-term increase in protein synthesis. Additionally, several other studies point to PGF2a, specifically, as being the prostaglandin most closely tied to increases in skeletal muscle protein synthesis7 8 9.

Studies with drugs that inhibit the conversion of arachidonic acid to prostaglandins perhaps give us an even better way of seeing just how important these hormones are to muscle growth. In March 2002 just such a study was published10. It involved a group of 24 recreationally active young male subjects, who were given maximum OTC doses of ibuprofen (1,200mg/day) or acetaminophen (4,000mg/day) and subjected to resistance training. These two popular over-the-counter pain relief medications are known to work by inhibiting the enzymes responsible for prostaglandin synthesis11 12. Amino acid turnover was measured for 24 hours following the bout of exercise, which allowed the investigators to determine what effect, if any, these drugs would have on protein breakdown and synthesis. It turned out that both ibuprofen and acetaminophen effectively blunted the normal post-exercise rise in protein synthesis, which was increased 76% above baseline in the group taking only the placebo. A follow up investigation using the same conditions and subjects demonstrated that both drugs blocked the normal post-exercise rise in PGF2a, specifically13. Together these studies show us how strongly prostaglandins actually support the basic process of muscle growth. Without them there is no growth; it is as simple as that.

*Release During Exercise *

The role arachidonic acid plays in muscle growth must be looked at as much more than just that of a precursor to prostaglandins. Skeletal muscle tissue has no capacity to actually store prostaglandins, so the only local source for PGF2a is the arachidonic acid that is retained in the outer phospholipid layer of each cell. Even more importantly, it is the stretching of muscle fibers during intense physical exercise that causes arachidonic acid to be released and metabolized to active prostaglandins. Arachiconic acid release is therefore the very first trigger in a long cascade that controls the rebuilding and strengthening of muscle tissue after exercise. A study conducted at the Rowett Research Institute in the U.K. illustrates this relationship . Here, researchers used similar muscle incubation and stretching techniques to the 1990 American Journal of Physiology study to demonstrate that it is arachidonic acid release, not stored prostaglandins, that serves as the core stimulus for protein synthesis. Their work was summarized by the participants well when they noted, ".the link between mechanical activity and protein synthesis. is most simply explained by the assumption that free arachidonic acid is released by stretching, is retained intracellularly and continues to be metabolized to the prostaglandins." Two additional studies by Palmer and colleagues at the Rowett Institute support the same conclusion .

*Exercise and AA Concentrations*

To make things a little more difficult for athletes, both animal and human studies show that exercise lowers the content of arachidonic acid in skeletal muscle tissue. One such investigation divided human subjects into exercise and sedentary (inactive) groups, giving both the same standardized diet with an equivalent makeup of fatty acids and arachidonic acid (total food intake varied slightly between groups). The sedentary group noticed about a 5% increase in arachidonic acid concentrations during the course of the study, while the exercise group exhibited a moderate 7-8% depletion of this fatty acid. This was in spite of the fact that the exercise group actually consumed 13% more food on average compared with the sedentary group, which would account for a slightly greater total intake of fatty acids. Since dienolic prostaglandin synthesis is inextricably tied to the amount of available arachidonic acid, lower levels can only result in less arachidonic acid being release with the stretching of eccentric exercise, as well as less muscle-building PGF2a being synthesized to increase muscle protein synthesis.

*AA Loading *

In June of 2001, a paper was published in the journal "Lipids" that reviewed many of the medical studies over the past few decades concerning the sources of arachidonic acid in the body . Among other things, this paper discussed several studies that looked at the effect of short-term diets very rich in arachidonic acid. In going over both animal and human data, the authors consistently noted strong increases in the arachidonic acid content of various body tissues with supplementation of higher levels than the normal diet would provide. One such concerned a series of studies actually, where human subjects ingested 1.7grams per day of arachidonic acid for 50 days . This extensive investigation reported that arachidonic acid at this level in the diet nearly doubled the arachidonic acid content of plasma phospholipid, and also significantly increased the content of this fatty acid in platelet, red blood cell, and tissue lipids.

Another investigation specifically looked at what effect high tissue concentrations of arachidonic acid would have on the prostaglandin system . Investigators loaded high levels of arachidonic acid in the body by requiring subjects to consume 6 grams daily for 2-3 weeks in the form of its ethyl ester. Researchers noted a significant retention of arachidonic acid in the lipids of all tissues measured. In addition, there was a significant increase in the output of prostaglandin metabolites during the course of the study (they looked at E series prostaglandin metabolites specifically). In 3 of the 4 subject s studied, the increase in prostaglandin output was a remarkable 47%, indicating a dramatic rise in the synthesis rate of these hormones. The authors concluded that supplementing precursor fatty acids in high levels augments the biosynthesis and function of prostaglandins. The arachidonic acid intake studies help us establish not only that we can use X-FACTOR to supplement normal dietary levels of this nutrient, but also that that it can be used to enhance our level of stored arachidonic acid in muscle tissue above normal and heighten the sensitivity of the prostaglandin system to exercise.

*Supplement Safety *

For those concerned that there might be immediate cardiovascular health concerns with taking a "red meat" nutrient like arachidonic acid, we should refer to a study conducted back in 1997 that looked very closely at the effect of high doses on blood lipoprotein and lipid values known to be risk factors for cardiovascular disease . This investigation, again, involved consuming 1.7grams per day, and ran for a period of 50 days. Noting that subjects were consuming this fatty acid in levels eightfold of the average western diet, researchers reported no adverse effects on plasma cholesterol or triglyceride concentrations at all. Both good (HDL) and bad (LDL) cholesterol seemed unaffected during the course of the study. Thus, we can conclude that while feeding increased amounts of arachidonic acid to healthy men or women will increase its content in tissue phospholipids, and by extension the responsiveness of the prostaglandin system dependent on this fatty acid, it does not appear that doing so involves any increased cardiovascular health risks. This product, however, is not recommended if you have diabetes, asthma, high blood pressure, high cholesterol, arthritis, heart disease, are pregnant, or are suffering from any inflammatory diseases. Consult with your physician before use if you are taking any medications, or suffer any health conditions where red meat consumption is restricted.

*What the Research Tells Us *

The above studies on prostaglandins and arachidonic acid have been taken from several different areas of medical research, and tie-in together to reveal the role this nutrient can play as a muscle-building supplement. They show not unfulfilled promises and the typical "yet another worthless fad supplement" scenario, but a scientifically well-supported new method for increasing muscle growth. To summarize what we have learned in their review, we can highlight several very important key points. 1) Prostaglandins are the very core stimulators of protein synthesis following exercise. 2) The synthesis of prostaglandins is dependent on levels of available arachidonic acid. 3) The body stores arachidonic acid in muscle tissue, not active prostaglandins. 4) Arachidonic acid is released from the outer phospholipid layer of muscle cells during the stretching caused by exercise. Once freed, it is rapidly converted to active prostaglandins. 5) Exercise lowers the levels of arachidonic acid in muscle tissue. 6) Consuming higher than normal levels of arachidonic acid will result in the greater retention of this fatty acid in body tissues, which can markedly enhance the output of anabolic prostaglandins in response to physical exercise.


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## Truewarrior1 (Jan 27, 2005)

yeah i caught this a while back think i posted the same stuff on here..the results people are having seem sound, 5 to 10lbs over a month or two. you cant take in any fish oils whilst using and you will be feeling your joints. theres been lots of discussion over at bb.com about this supplement with the person who makes it.


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## ChefX (Jan 10, 2005)

Paul, IMO - aa eh?

I suggest you go do some reads on aspirin and its effect on the body. You will find what was listed in that article to be a tad off, ok not a tad but lots. Fish oils exert their effect like aspirin on eicasanoid production which contraols and reduces AA... so why reduce AA... because higher AA gets yoiu lower HDL to LDL ratio and less test... not more plus it leads to over clotting (can you say stroke/heart attack) it leads to hardening of arteries and cellular walls (no growth) and more.

Some one got ahold of some very very powerful information and twisted it to sell a supplement. This is getting dangerous.

There are tons of studies now on this showing aa is what we want to control for health at all, and by controlling aa we get a much higher release of hgh to insulin ratio and with that better recovery and growth, plus it shows that aa reduction withthe right diet can increase test production.


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## SD (Sep 3, 2004)

This stuff sounds bogus,

If you want to raise AA levels you can do it using static contraction! In a study on cats SC raised AA levels from 4.4 nmol/g to 10.3 nmol/g. Another reason to go static now and again 

*D. M. Rotto, K. D. Massey, K. P. Burton and M. P. Kaufman (1989) *Static contraction increases arachidonic acid levels in gastrocnemius muscles of cats. Journal of Applied Physiology, Vol 66, Issue 6 2721-2724

Other than that, the research I can see hasn't looked at it as an ergogenic aid to bodybuilders at all.

SD


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## ChefX (Jan 10, 2005)

Part of the problem is that AA is pro inflamation and we know that reduction of inflamation speeds recovery and growth.

Arachidonic acid - This particular polyunsaturaed fat may be the most dangerous fat know when consumed in excess and is known as an Omega 6 fat. In fact, you can inject virtually every type of fat (even saturated fat and cholesterol) into rabbits and nothing happens. However, if you inject (AA) arachidonic acid into the same rabbits they are *dead within three minutes*. The human body needs "some" arachidonic acid, but too much can be toxic.

Ironically, the higher your insulin levels, the more your body is stimulated to make increased levels of arachidonic acid. (AA) is a long-chain omega-6 fatty acid. Enchaned production of good eicosanoids requires the presence of EPA and DHA long chain "omega 3" fats, found in fish oil.


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## Captain Hero (Jun 13, 2004)

ChefX said:


> Part of the problem is that AA is pro inflamation and we know that reduction of inflamation speeds recovery and growth.
> 
> Arachidonic acid - This particular polyunsaturaed fat may be the most dangerous fat know when consumed in excess and is known as an Omega 6 fat. In fact, you can inject virtually every type of fat (even saturated fat and cholesterol) into rabbits and nothing happens. However, if you inject (AA) arachidonic acid into the same rabbits they are *dead within three minutes*. The human body needs "some" arachidonic acid, but too much can be toxic.
> 
> Ironically, the higher your insulin levels, the more your body is stimulated to make increased levels of arachidonic acid. (AA) is a long-chain omega-6 fatty acid. Enchaned production of good eicosanoids requires the presence of EPA and DHA long chain "omega 3" fats, found in fish oil.


whats an eicosanoid Chef?


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## ChefX (Jan 10, 2005)

Ok you asked!!!

(this is from Dr. Sears materials... I was going to edit the parts where he lied about history but thought it would be fine this way. As many of you know my base in medicine comes from this research which, my specialty being dietary manipulation of these microhormones. cheers)

Eicosanoids

Strange, mysterious, and almost mystical, eicosanoids are the key to our health because they control the flow of information in our Biological Internet. Why are eicosanoids so important? They were the first hormones developed by living organisms more than 550 million years ago. As such they can be considered "super-hormones" because they control the hormonal actions of other hormones. Furthermore, you don't have an eicosanoid gland since every one of your 60 trillion cells can make eicosanoids.

Even though they are earliest hormones (dating from 550 million years ago), eicosanoids only were identified in the 20th century starting with the discovery of essential fatty acids in 1929. It was found that if fat in the diet was totally removed, rats would soon die. Adding back certain essential fats (then called Vitamin F) was found to enable fat-deprived rats to live. Eventually as technologies advanced, researchers realized that essential fats were composed of both Omega-6 and Omega-3 fatty acids that both needed to be obtained in the diet because the body could not synthesize them. The word eicosanoids is derived from the Greek word for 20 which is eicosa, since all of these hormones are synthesized from essential fatty acids that are 20 carbon atoms in length.

The first actual eicosanoids were discovered in 1935 by Ulf von Euler. These first eicosanoids were isolated from the prostate gland (an exceptionally rich source of eicosanoids), and were called prostaglandins (a small subset of the much larger family of eicosanoids). Since it was thought at that time that all hormones had to originate from a discrete gland, it made perfect sense to name this new hormone a prostaglandin. With time it became clear that every living cell in the body could make eicosanoids, and that there was no discrete organ or gland that was the center of eicosanoid synthesis.

To date biochemists have identified more than 100 eicosanoids and are finding more each year. The breakthrough in eicosanoids research occurred in 1971 when John Vane finally discovered how *aspirin* (the wonder drug of the 20th century) actually worked: It changed the levels of eicosanoids. The 1982 Nobel Prize in Medicine was awarded to Vane and his colleagues Bengt Samuelsson and Sune Bergelson for their discovery of how eicosanoids play a role in human disease.

This is where the journey with eicosanoids first started twenty years ago. It was apparent that if certain "bad" eicosanoids were associated with chronic disease conditions (like heart disease, cancer, arthritis, and so on), then the key to wellness would be to induce the body to make more "good" eicosanoids and fewer "bad" eicosanoids. Rather than using drugs to achieve that goal, It was reasoned they could use food as if it were a drug. All we needed to do was figure out the right balance of protein, carbohydrate, and fat that would turn food into this beneficial drug. After more than 20 years, we got the zone based diets (isocaloric, zone, diatia ect ect)

Of course, our colleagues in academic medicine didn't quite share the initial enthusiasm. Almost overnight, we went from being a respected research scientists with numerous patents in the area of intravenous drug delivery systems for cancer drugs, to being called a snake-oil salesmen because of our constant refrain that the appropriate diet could change the balance of eicosanoids throughout the body. Part of the problem was that very few of them even knew what an eicosanoid was.

I believe that the foundation of 21st century medicine will be the manipulation of eicosanoids. Yet ask most physicians and medical researchers what an eicosanoid is, and you will usually get a blank stare. I guess they're not familiar with the Nobel Prize winning research. As unknown as they are to the medical community, eicosanoids are the hormones that maintain the information fidelity of your Biological Internet, which means they become the key to health and longevity.

Why are eicosanoids so unknown if they are so important? First, they are made, act, and self-destruct within seconds making them very difficult to study. Second, they don't circulate in the blood stream making it extremely difficult to sample them. Finally, they work at vanishingly low concentrations making it almost impossible to detect them. Despite these barriers, more than 87,000 articles on eicosanoids have been published in peer-reviewed journals. So, the basic research community is interested in eicosanoids even if your doctor never learned about them in medical school.

Eicosanoids encompass a wide array of hormones, many of which endocrinologists have never heard of. They are derived from a unique group of polyunsaturated essential fatty acids containing 20 carbon atoms. The different classes of eicosanoids are shown below

Subgroups of Eicosanoids

Prostaglandins

Thromboxanes

Leukotrienes

Lipoxins

Hydroxylated fatty acids

Aspirin-triggered Epi-lipoxins

Isoprostanoids

Epoxyeicosatrienoic acids

Endocannabinoids

Now if you mention the word prostaglandins to physicians, they are likely to have heard of those particular hormones. However, prostaglandins are only a small subgroup of the eicosanoid family. Some of the other subgroups have been discovered only recently. As an example, aspirin-triggered epi-lipoxins are the ones that give rise to the powerful anti-inflammatory properties described in the chapter on heart disease were discovered only a few years ago.

The glory days of eicosanoid research lie ahead with new eicosanoids continually being discovered and a growing realization of the vast role these hormones play in controlling other hormonal systems. This fact has not been lost upon pharmaceutical companies, which have already spent billions of dollars trying to develop eicosanoid-based drugs. Eicosanoids as drugs, however, have a very limited role in the world of pharmaceuticals. They are not only too difficult to work with, but they are also too powerful to be used as a drug. (but food as a drug that controls them isn't)

There does remains one way to directly manipulate eicosanoids: your diet. The reason why your diet can be successful where the largest drug companies have been unsuccessful is based on evolution. Eicosanoids were the first hormonal control system that living organisms developed. You can't have organized life unless you have cell membranes separating the internal workings of the cell from its environment. Since all cell membranes contain fatty acids (including the building blocks of eicosanoids, which are known as essential fatty acids), the cell's own membrane became the ideal reservoir for eicosanoid synthesis since you could always be certain that the raw materials for making these hormones were close by.

As autocrine hormones, eicosanoids' mission is to be secreted by the cell to test the external environment and then report back to the cell what was just outside by interacting with its receptor on the cell surface. Based on that information, the cell could then make the appropriate biological action (via the appropriate second messenger) to respond to any change in its environment.

In biotechnology, one of the hot research areas today is the field of biological response modifiers. Eicosanoids represent the first (and probably the most powerful) biological response modifiers developed by living organisms. In fact, many of the eicosanoids that we make in our bodies today are identical to ones made by sponges beginning hundreds of millions of years ago.

The reason why eicosanoids play such a central role in our physiology is due to the second messengers that certain eicosanoids generate. There are a variety of eicosanoid receptors on the surface of the cell, and depending on which eicosanoid interacts with the receptor, a specific second messenger is then synthesized by the cell. Sometimes a second messenger, such as cyclic AMP is generated, and sometimes a totally different second messenger, such as the DAG and IP3 system, is generated. If one second messenger goes up, then the other goes down. In essence, the complexity of your Biological Internet is reduced to a digital system consisting of green and red lights.

Those eicosanoids that generate increased production of cyclic AMP are your key to maintaining wellness. Why? Cyclic AMP is the same second messenger used by a number of endocrine hormones in the body to translate their biological information to the appropriate target cell. By maintaining adequate cellular levels of those eicosanoids that increase cyclic AMP levels, you are guaranteed that a certain baseline level of cyclic AMP is always present in a cell. Thus, it's far more likely that the overall cyclic AMP level in the cell will be high enough to ensure that an appropriate biological response (i.e. better hormonal communications) is generated.

How can you tell a "good" eicosanoid from a "bad" eicosanoid?

An eicosanoid's effect on second messengers becomes the definition of a "good" or "bad" eicosanoid. A "good" eicosanoid will increase the levels of cyclic AMP in a cell, whereas a "bad" eicosanoid will decrease the levels of cyclic AMP through the elevation of the levels of the IP3/DAG second messengers. The table below shows a listing of the types of "good" and "bad" eicosanoids and their receptors they interact with.

Receptors for "Good" and "Bad" Eicosanoids

Receptor Effect on cyclic AMP

"Good" Eicosanoids

PGE1 EP2, EP4 increase

PGI2 IP increase

PGD2 DP increase

"Bad" Eicosanoids

TXA2 TP decrease

PGE2 EP1, EP3 decrease

PGF2a FP decrease

LTB4 BLT decrease

LTC4, Cys-LTI decrease

LTD4, LTE4 Cys-LT2 decrease

Once an eicosanoid interacts with its unique receptor, a second messenger is then synthesized inside in the target cell. If a "good" eicosanoid interacts with the right receptor, then cyclic AMP is the second messenger that is formed. On the other hand, if a "bad" eicosanoid interacts with its receptor then cyclic AMP levels are decreased. Adding further to this complexity is that some eicosanoids such as PGA and PGJ are cyclopentenone eicosanoids. These eicosanoids don't have cell receptors on the surface as they can directly enter into the cell where they can interact with the cell's nucleus to effect cellular growth and differentiation. Since there is no discrete eicosanoid "gland", there is no central site that turns "on" or "off" eicosanoid action. Nature solved this problem by developing different types of eicosanoids that have diametrically opposed physiological actions. It is the balance of these opposing actions of different eicosanoids to remain an equilibrium of biological activity. These differences in biological actions are the foundation for the eicosanoid "axis".

This eicosanoid "axis" is composed of "good" eicosanoids on one side and "bad" eicosanoids on the other. In the absence of the evolutionary development of more advanced hormonal systems (like corticosteroids) to control this eicosanoid activity, this balance of "good" and "bad" eicosanoids was the best solution that could be done at the time. Obviously, there is no such thing as an absolutely "good" eicosanoid nor an absolutely "bad" eicosanoid, anymore than there is a moral attachment to "good" and "bad" cholesterol.

Most chronic diseases are a consequence of an imbalance of "good" and "bad" eicosanoids. I have already discussed in this book the role of eicosanoids in heart disease, cancer, diabetes, arthritis, and depression among others. The 1982 Nobel Prize in Medicine provided me an insight into the molecular nature of chronic disease since it could be seen as an imbalance in eicosanoid levels. It became apparent to me at the same time that the appropriate balance of eicosanoids could be used to provide a molecular definition of wellness. In essence, the more the balance of eicosanoids is tilted toward "bad" eicosanoids, the more likely you are to develop chronic disease. Conversely, the more the balance is tilted toward "good" eicosanoids, the greater the chance that you'll achieve wellness and longevity. The AA/EPA ratio will indicate where you stand in terms of such a balance.

If you are skeptical about the statement that eicosanoids play such a fundamental role in a such number of diverse disease conditions, then ask any physician what happens when they give a high dose of corticosteroids to a patient for more than 30 days. The answer will be physiological devastation, if not death. This occurs because corticosteroids have only one mode of action, they knock out all eicosanoid production -- "good" and "bad" by inhibiting the release of essential fatty acids from cell membrane. This chokes off all supply of precursors to make any type of eicosanoid. Without eicosanoids, you can't survive.

How Eicosanoids are Synthesized

Since eicosanoids are produced in every cell-not one specific gland-- it's as you have 60 trillion separate eicosanoid glands capable of making these exceptionally powerful hormones. Unlike the endocrine hormones, which are under control of the hypothalamus, there is no such central control on eicosanoids. Rather than responding to some master signal, each cell responds to changes in its immediate environment. The first step in generating a cellular response is the actual release of an essential fatty acid from the phospholipids in the cell membrane. The enzyme responsible for the release of the essential fatty acid is called phospholipase A2.

Since there is no feedback loop to stop the production of eicosanoids, the only way to inhibit their release from the membrane is by the production of corticosteroids (such as cortisol) from the adrenal gland, which causes the synthesis of a protein (lipocortin) that inhibits the action of phospholipase A2. By inhibiting this enzyme, which releases essential fatty acids from the cell membranes, you choke off the supply of a substrate required for all eicosanoid synthesis. Obviously, if you are overproducing corticosteroids (or taking corticosteroid drugs), you will bring all eicosanoid synthesis to a crashing halt, which can cause the shut down of your immune system.

The most powerful eicosanoid modulating drugs are corticosteroids. As I mentioned above, they inhibit the release any essential fatty acid so that no eicosanoids can be synthesized. Obviously, if you have intense pain or inflammation, this may be your only course of action on a short-term basis. Over the long term, corticosteroid therapy lowers the response of your immune system, decreases cognitive function, increases fat stores, thins the skin, and accelerates osteoporosis. In fact, if you give a single injection of corticosteroids to healthy individuals, their lymphocytes will be very similar to those in AIDS patients within 24 hours.

Enzymes that Make Eicosanoids

There are three primary pathways an essential fatty acid (composed of a string of 20 carbon atoms), once released from the cell membrane, can follow. The first is via the cyclo-oxygenase system (i.e. COX) that make prostaglandins and thromboxanes. In this pathway the highly contorted essential fatty acid is closed upon itself to form a prostanoid ring. The second is through the 5-lipo-oxygenase (5-LIPO) pathway that makes leukotrienes. There is a third pathway in which the 20-carbon essential fatty acid is simply modified via either the 12 or 15-lipoxygenase (12 or 15-LIPO) enzymes as in the case of hydroxylated essential fatty acids. It is via this third pathway that many of the newly discovered eicosanoids are made. These pathways are shown below.

Types of Eicosanoid Synthesizing Enzymes

Long-chain Essential Fatty Acids

COX 5-LOX 12 and 15 LOX

Prostaglandins Leukotrienes Lipoxins and

and Thromboxanes Hydroxylated Fatty Acids

Certain drugs can inhibit the cyclo-oxygenase pathway of this eicosanoid formation. The most well known is aspirin which literally destroys a cyclo-oxygenase enzyme on a one-on-one basis. This is what is known as a suicide inhibitor. When you are suffering from a headache or arthritic pain, you are overproducing "bad" eicosanoids, but in particular "bad" prostaglandins. The aspirin temporally shuts down all prostaglandin formation (but not leukotriene formation), until the cell can make more of the cyclo-oxygenase enzyme to replace the ones destroyed by the aspirin. However, you can't be using these suicidal soldiers forever, as aspirin also shuts down the synthesis of "good" prostaglandins, especially those that protect the stomach from dissolving itself. When that happens, you get internal bleeding. This is why there are more than 10,000 deaths per year associated with the over-use of aspirin. Other drugs known as non-steroidal anti-inflammatory drugs (NSAID's) also inhibit the cyclo-oxygenase enzyme but not the lipo-oxygenase enzyme that makes leukotrienes. The common names for these NSAID's are Motrin, Advil, Aleve, and others. Continued use of these NSAID's generates the same problems as does long-term aspirin use.

COX Enzymes

The most common types of anti-inflammatory drugs are those that can only affect those eicosanoids that are synthesized via the cyclo-oxygenase enzyme or COX. It was recently discovered there are two forms of this enzyme known as COX-1 and COX-2. COX-1 enzymes are a constant fixture of the vascular cells that line the bloodstream or in stomach cells that secrete bicarbonate to neutralize stomach acid. COX-2 appears to be an enzyme that is synthesized only in response to inflammation. Standard drugs like aspirin and NSAID's (like Advil) don't discriminate between these specific forms of the COX enzyme, which is why they have side-effects associated with their long-term use.

For example, it appears that the anti-cancer benefits of aspirin may stem from its inhibition of COX-2, whereas the side-effects (like an increased risk of internal bleeding) come from its simultaneous inhibition of COX-1. However, this same inhibition of the COX-1 enzyme appears to convey the cardiovascular benefits associated with aspirin. This may explain why long-term use of COX-2 inhibitors may not work to decrease heart attack rates: They don't target the COX-1 enzyme. Weighing the risks against the benefits presents a dilemma associated with all drugs that affect eicosanoid synthesis.

LOX Enzymes

Unlike inhibitors of the COX enzymes, there are very few inhibitors of the LOX enzymes. Since leukotrienes (particular LTB4) represent a primary mediator of pain, then the only way to affect their production is to use corticosteroids with all of their associated side effects. However, the leukotrienes synthesized from EPA are physiologically neuter compared to those derived from arachidonic acid. This is why the AA/EPA ratio is a very good indicator of the body's potential to prevent the over-production of leukotrienes without using resorting to the use of corticosteroids.

Drug companies are racing to develop new patentable drugs--ones that affect the downstream enzymes that control eicosanoid production from arachidonic acid. Overlooked in this frenzy by the drug companies seeking new and more expensive drugs to go downstream to modify eicosanoid synthesis, is that there is an existing "drug" that can achieve all of these benefits without any side effects. This is because it goes upstream to modify eicosanoid production by reducing arachidonic acid levels. That "drug" is high-dose fish oil since the elevated levels of EPA will reduce the production of "bad" eicosanoids (such as PGE2 and LTB4) derived from arachidonic acid.

Synthesis of Essential Fatty Acids

To understand the importance of diet in controlling these eicosanoids and re-establishing an appropriate eicosanoid balance, we have to understand how the actual precursors of eicosanoids are made. To begin with, all eicosanoids ultimately are produced from essential fatty acids that the body cannot make, and therefore must be part of the diet. These essential fatty acids are classified as either Omega-3 or Omega-6 depending upon the position of the double bonds within them. However, typical essential fatty acids are only 18 carbons in length and must be further elongated to 20-carbon fatty acids by the body before eicosanoids can be made. Remember, all eicosanoids come from essential fatty acids that are 20 carbon atoms in length. It is just not the number of carbon atoms that count, but also their configuration. Eicosanoid precursors must have a certain spatial configuration with at least three conjugated double bonds in order to be converted into an eicosanoid. How your diet controls the formation of dietary essential fatty acids into the actual 20-carbon atom precursors of eicosanoids is a complex story.

The discovery of essential fatty acids was first reported in 1929. At that time essential fatty acids were called Vitamin F. But Vitamin F was useless unless transformed into an eicosanoid. Thus began a continuing 70-year journey to understand how your diet does three things: controls eicosanoid formation; alters eicosanoid balance in the body; and determines how eicosanoids become a central players in your health.

The differences between the two classes of essential fatty acids, Omega-6 and Omega-3, are based on the position of the double bonds within the fatty acid molecule. This is important since it is the positioning of these double bonds that dictates their three-dimensional structure in space that ultimately determines how they interact with their appropriate receptors. Although the synthesis of essential fatty acids use the same enzymes, their metabolic pathways are quite different. The metabolism of long-chain Omega-3 fatty acids are more complex, so let's start with the simpler pathway to make Omega-6 fatty acids.

Omega-6 Fatty Acids

There are two key steps in this process that determine the amount of eicosanoid building blocks that will be made. These are known in biochemistry as "rate-limiting steps". The first rate-limiting step is controlled by the enzyme delta-6-desaturase. This enzyme inserts a necessary third double bond in the essential fatty acid in just the right position to begin bending inward and forms gamma linolenic acid (GLA) from linoleic acid as shown in the figure below.

Synthesis of Omega-6 essential fatty acids into eicosanoid precursors

Linoleic Acid (C18:2)

Delta-6 desaturase

Gamma Linolenic Acid (GLA) (C18:3)

Elongase

Dihomo Gamma Linolenic Acid (DGLA) (C20:3)

Delta 5-desaturase

Arachidonic Acid (AA) (C20:4)

"Good" Eicosanoids "Bad" Eicosanoids

(The number after the C tells how many carbon atoms the essential fatty acid contains, and the number after the colon tells how many double bonds there are in the essential fatty acid)

I define an activated essential fatty acid as any essential fatty acid that has this new double bond inserted by the delta-6-desaturase enzyme. This is because this new double bond starts bending the essential fatty acid to get the appropriate spatial configuration required to make an eicosanoid. Once this new double bond has been inserted into a short-chain essential fatty acid, then very small amounts of these activated essential fatty acids can profoundly affect eicosanoid balance in your body.

However, there are many factors that can decrease the activity of delta-6-desaturase enzyme. The most important factor is age itself. There are two times in your life during which this enzyme is relatively inactive. The first is at birth. For the first six months of life, the activity of this key enzyme in the newborn is relatively low. But this is also the time at which maximum amounts of long-chain essential fatty acids are required by the child since the brain is growing at the fastest possible rate, and these long-chain essential fatty acids are the key structural building blocks for the brain. Nature has developed a unique solution to this problem: mother's breast milk. Breast milk is very rich in GLA and other long-chain essential fatty acids such as the EPA and DHA. By supplying these activated essential fatty acids through the diet, this early inactivity of the delta-6-desaturase enzyme is overcome.


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## ChefX (Jan 10, 2005)

The second time in your life during which the activity of this enzyme begins to decrease is after the age of 30. Eicosanoids are critical for successful reproduction. Since the primary child-bearing years for women are between the ages of 18 and 30, it makes good evolutionary sense to start turning down the activity of a key enzyme needed to make the precursors of eicosanoids required for fertility after age 30.

The delta-6-desaturase enzyme can also be inhibited by viral infection. The only known anti-viral agents are "good" eicosanoids such as PGA1 because of their ability to increase cyclic AMP levels that keep viral replication under control. On the other hand, if you are a virus, then your number-one goal is to inhibit the formation of this type of eicosanoid. This is exactly what many viruses do by inhibiting the delta-6-desaturase enzyme. By doing so, the virus has devised an incredibly clever way to circumvent the body's primary anti-viral drug (i.e. PGA1).

The final factor that can decrease the activity of delta-6-desaturase is the presence of two types of fatty acids in your diet; trans fats and Omega-3 fats. Trans fatty acids don't exist naturally but are produced by food manufacturers. They are essential Omega-6 fatty acids that have been transformed by a commercial process (known as hydrogenation) into a new spatial configuration that is more stable to prevent oxidation. The increased stability of these fatty acids makes them ideal for processed foods, but also makes trans fatty acids strong inhibitors of the delta-6-desaturase enzyme. Trans fatty acids occupy the active site of the delta-6-desaturase enzyme, thus preventing the formation of the activated essential fatty acids required for eicosanoid synthesis. In essence, trans fatty acids can be viewed as anti-essential fatty acids because of their inhibition of eicosanoid synthesis. This may be the reason why they are strongly implicated in the development of heart disease. How do you know if a food product you're consuming contains trans fatty acids? Look for the word "partially hydrogenated vegetable oil" on the label. If it is there, then you know the food contains trans fatty acids. Surprisingly, Omega-3 fats can also inhibit the delta-6-desaturase enzyme activity in producing GLA since short-chain Omega-3 fatty acids such as alpha linolenic acid (ALA) preferentially bind to the enzyme thus decreasing GLA synthesis, and long-chain Omega-3 fatty acids such as DHA act as feedback inhibitors of the enzyme.

The journey toward becoming an eicosanoid is still far from over after passing this first hurdle of making GLA. Once GLA is formed, it is rapidly elongated into dihomo gamma linolenic acid (DGLA), which is the precursor to many of the "good" eicosanoids. However, DGLA is also the substrate for the other rate-limiting enzyme in essential fatty acid cascade in the chart above. That enzyme is called delta-5-desaturase. The activity of this enzyme ultimately controls the balance of "good" and "bad" eicosanoids thus making it the primary target to alter its activity by your diet if your goal is to treat chronic disease and promote wellness.

This is because the end product that the delta-5-desaturase enzyme that produces from DGLA is arachidonic acid (AA). DGLA is the building block of many of the "good" eicosanoids, whereas AA is the building block of "bad" eicosanoids. Thus excess amounts of AA can be one of your worst hormonal nightmares. Ultimately, it is the balance between DGLA and AA in every one of your 60 trillion cells that determines which types of eicosanoids you will produce. You need some AA to produce some "bad" eicosanoids, but in the case of excess production of AA, the balance of eicosanoids will shift toward accelerated aging and chronic disease.

Some of the Eicosanoids Derived from Arachidonic Acid

Arachidonic Acid (AA)

COX 5-LOX 12 and 15 LOX

PGH2 TXA2 LTB4 12-HETE Lipoxin

PGD2 PGI2

LTBC4 15-HETE

PGJ2 PGF2a PGE2

PGB2 LTBD4

PGA2

LTBE4

Many of these eicosanoids derived from arachidonic acid can be considered to be "bad" because they promote inflammation (PGE2 and LTB4) and decrease blood flow (TXA2). In addition, the inflammatory "bad" eicosanoids can also promote the release of other pro-inflammatory cytokines.

While there is bewildering complexity of eicosanoids from ararchidonic acid, there are a very limited number of eicosanoids that come from dihomo gamma linolenic acid (DGLA) as shown below

Eicosanoids from DGLA

Dihomo Gamma Linolenic Acid (DGLA)

COX LOX

PGH1 15-OH Triene

PGE1

PGA1

The primary eicosanoid derived from DGLA is PGE1, one of the most highly studied "good" eicosanoids as it a very powerful vasodilator and inhibitor of platelet aggregation. It also reduces the secretion of insulin and increases the synthesis of wide variety hormones that normally decrease during the aging process. PGE1 is able to achieve these diverse functions because it causes an increase in cyclic AMP production. PGA1 is the most powerful suppressor of viral replication, especially HIV transcription, as well as inhibiting nuclear transcription factor NFkappaB necessary for synthesis of a wide variety of pro-inflammatory cytokines. And finally the 15-LOX enzyme can convert DGLA into a powerful inhibitor of the 5-LOX enzyme that decreases leukotriene synthesis. You can see that having higher levels of DGLA compared to AA which play an important factor for decreasing inflammation and increasing blood flow.

So how do you help your body block excess AA formation and tilt the balance back toward a favorable DGLA/AA ratio? By making sure your diet has adequate amounts of EPA. The importance of EPA is that it acts as a feedback inhibitor of the delta-5-desaturase enzyme. The higher the concentration of EPA in the diet, the more the delta-5-desaturase enzyme is inhibited, and the less AA is produced. As a result, the presence of EPA in the diet allows you to control the rate of AA production derived from DGLA, and thus generate a favorable DGLA to AA ratio in each cell membrane. This is why the AA/EPA ratio in the blood is such a powerful predictor of chronic disease.

Omega-3 Fatty Acids

The synthesis of long-chain Omega-3 fatty acids is much more complex as shown below.

Synthesis of Long-Chain Omega-3 Fatty Acids

Alpha Linolenic Acid (ALA) (C18:3)

Delta-6 desaturase

Steradonic Acid (C18:4)

Elongase

Eicosatretaenoic Acid (C20:4)

Delta 5-desaturase

Eicosapentaenoic Acid (EPA) (C20:5)

Elongase

C22:5

Elongase

C24:5

Delta-6 desaturase

C24:6

Perioxsomal degradation

Docosahexaenoic Acid (DHA) (C22:6)

Perioxsomal degradation

Eicosapentaenoic Acid (EPA) (C20:5)

The synthesis of EPA is seemingly relatively straight-forward from the short-chain Omega-3 fatty acid, alpha linolenic acid (ALA), just as the synthesis of arachidonic acid is from its short-chain precursor, linoleic acid. However, alpha linolenic acid is an inhibitor of the delta-6-desaturase enzyme, just as EPA is a feedback inhibitor of the delta-5-desaturase enzyme. This feedback inhibition makes the formation of EPA much more difficult that it should be. This is why studies comparing dietary intake of ALA versus EPA have indicated that the efficiency of making EPA from ALA is extremely limited. Therefore if you want get the greatest benefit of EPA, it will have to come from eating fish oil as opposed to vegetable sources rich in ALA (such as flaxseed).

Now it gets even more complex when going further on to make the DHA that is critical for the brain. The EPA must be elongated and then converted again by the delta-6-desaturase enzyme to the precursor of DHA which then must be shortened by perioxsomal enzymes into DHA. The result is that the synthesis of DHA from ALA is even more difficult than the synthesis of EPA (which isn't very good to begin with). Furthermore, DHA acts as a feedback inhibitor of the delta-6-desaturase enzyme that further reduces the flow of ALA to EPA and DHA. You can begin to see why until modern man starting eating shellfish some 150,000 years ago, that his ability to have adequate levels of long-chain Omega-3 fatty acids for his brain was highly compromised.

DHA can also be retro-converted into EPA by the same perioxosmal enzymes used necessary to make DHA in the first place, Although the process is not that efficient, but at least it provides a mechanism by which vegetarian sources (genetically modified algae) of DHA can provide EPA. This retroconversion process appears to be a more efficient way of making EPA for someone following a vegetarian diet than is its synthesis from ALA.

This is why long-chain Omega-3 fatty acids, like EPA, are so important in my dietary program. They inhibit the delta-5-desaturase enzyme thereby restricting the flow of any Omega-6 fatty acids into arachidonic acid, which therefore decreases the production of "bad" eicosanoids. As long as you are consuming very moderate amounts of Omega-6 fatty acids with equal amounts of EPA, then those dietary Omega-6 fatty acids in your diet tend to accumulate at the level of DGLA (because of the inhibition of delta-5-desaturase by the EPA), which increases the production of "good" eicosanoids. However, the total of amount of Omega-3 and Omega-6 fatty acid you need is relatively low. This means you still have to add some extra fat to your diet to help slow the rate of entry of carbohydrate to control insulin secretion. And the fat should be primarily monounsaturated fat. Monounsaturated fats can't be made into eicosanoids ("good" or "bad"). Thus by having no effect on eicosanoids nor insulin, monounsaturated fats can provide the necessary amount of fat for controlling the entry rate of carbohydrates into the bloodstream without disturbing the hormonal balances that you are trying to achieve through the OmegaRx Zone.

The Spillover Effect

In the early days, I thought that simply controlling the ratio of EPA and adding the right amount of GLA would be all that I needed to control eicosanoids. Taking all the data into account, including the increasingly massive over-consumption of Omega-6 fatty acids in general, I believed that a 4:1 ratio of EPA to GLA should do the trick. I thought one ratio would work for everyone. This was obviously flawed thinking in retrospect, but since I was coming from my background in pharmaceutical drug delivery, it seemed logical at the time. So I started out with this ratio, made some soft gelatin capsules containing both fish oil (the source of EPA) and borage oil (the source of GLA), and found some friends who were willing to be guinea pigs. I gave them my standard phrase, "Trust me".

Since I was only working with changing fatty acid levels during this early phase of my research, my initial observations on eicosanoids were not confounded by other potentially hormonally modulating approaches, like controlling insulin or restoring endocrine hormone levels. I had a very targeted approach to focus solely on manipulating eicosanoid levels through dietary supplementation with defined amounts of activated essential fatty acids. And many of the physiological changes I observed occurred within weeks, if not days.

The time frame for these physiological actions was important because it was much faster than the reported responses for treatments that focus on the restoration of endocrine hormones. Those changes usually take weeks, if not months, to see measurable effects.

After several months, however, I noticed that strange things seemed to be happening. Virtually everyone who took the combinations of EPA and GLA felt much better initially. After all, they were now making more "good" and fewer "bad" eicosanoids since I was changing the DGLA/AA balance in the cells. With time, some individuals mentioned that they seemed to have stabilized or that they even saw a drop-off in the early benefits they first experienced. Nonetheless, they still felt better than before they started. However, there was another smaller group, who saw their initial benefits erode completely and actually began to feel worse than when they started. Some of my friends were no longer quite so friendly, until I figured out what was happening. I called it the "spillover" effect.

Initially, as the ratio of DGLA to AA improves, the person begins making more "good" eicosanoids and fewer "bad" ones. Everything just keeps getting better. But there will be some point in time, depending on your biochemistry and gender, that the DGLA to AA ratio begins to degrade as more of the DGLA gets converted into AA. They still feel better than when they started, but not quite as good as they first did. For some individuals, this degradation of the DGLA/AA ratio continues to the point that they begin to feel worse than when they first started the program because they are now making many more "bad" eicosanoids. This is shown in the figure below.

These particular individuals developed a buildup of DGLA in their cells. The increased levels of DGLA were providing more substrate for the delta-5-desaturase enzyme to make more AA. The increase in DGLA was overwhelming the amount of EPA being supplied to inhibit the delta-5-desaturase enzyme. This spillover effect seemed to occur more often in females than in males. So much for the "one size fits all" ratio of GLA to EPA.

So I decided that if one size does not fit all, I had better start making a wide array of different EPA and GLA combinations and fine-tune them for each individual. But how could I do this? Fortunately eicosanoids do leave a biochemical audit trail that gives an insight into their actual balance in different organs in the body. That's what led me to develop the Eicosanoid Status Report to provide me with information on how to alter the amounts and ratios of activated essential fatty acids to fine-tune these exceptionally powerful hormones. (Now the AA/EPA test makes it even more precise.)

By 1989, I thought I had finally gotten this concept down to a science. A more complex science than I had originally thought, but one still governed by some basic biochemical rules. However what finally gave me the insight for the OmegaRx Zone was my work with elite athletes.

I began to notice that some of the elite athletes I was working with would have great training sessions, but then not do as well during competition. Others would do extremely well. When I started to ask them if they were doing anything different from a dietary standpoint prior to competition, it turned out that those who were carbohydrate-loading prior to a competition always appeared to do worse than those who maintained a consistent diet. I racked my brain trying to understand what had gone wrong or what had changed to explain this sudden shift in their eicosanoid status. Then it struck me. It was carbohydrate-loading that was increasing their insulin levels. This also explained the rapid decrease in the performance of the Stanford University swimmers who switched off my dietary recommendations and went back to eating dorm food composed primarily of high-density carbohydrates.

A trip to the bowels of the MIT library confirmed my suspicion. There I found previously published research that demonstrated that high levels of insulin activate the delta-5-desaturase enzyme, whereas glucagon inhibits this enzyme's activity. All the hormonal benefits I had carefully crafted for each athlete to manipulate their ratios of DGLA to AA were being undermined by the surge of insulin caused by their elevated carbohydrate intake. This increase in insulin stimulated the delta-5-desaturase enzyme to increase the production of AA at the expense of DGLA. For these athletes, the result was that a highly favorable DGLA to AA ratio created during training quickly became a very undesirable ratio at the time competition. It was the same spillover effect that I had observed in the early days of learning how to fine-tune eicosanoid levels. It was at that point I knew that I would never be able to control eicosanoid levels without controlling insulin first. It was back to the drawing board.

Was there any confirming evidence that high levels of insulin would affect the DGLA to AA ratio in humans? Fortunately, that information was published in 1991. The goal of that research was to maintain a high level of insulin for six hours in both normal subjects and patients with Type 2 diabetes (who are characterized by excessive insulin levels After only six hours of exposure to elevated insulin levels, the ratio of DGLA to AA in the bloodstream in both healthy individuals and Type 2 diabetics had dropped by nearly 50 percent. The elite athletes who were carbo-loading prior to competition were suffering the same decrease in DGLA/AA ratios by eating more high-density carbohydrates (grains, pasta, and starches), thus increasing insulin, which caused a rapid deterioration of their DGLA/AA ratios.

So now the metabolism of activated essential fatty acids had to be modified to take into account the role of insulin and glucagon on the delta-5-desaturase enzyme. This is shown below.

Effect of Elevated Insulin on the Metabolism of Activated Essential Fatty Acids

Dihomo Gamma Linolenic Acid (DGLA)

Delta-5 Desaturase

Activated by Insulin

Inhibited by EPA

Arachidonic Acid (AA)

Insulin was an activator of the delta-5-desaturase enzyme. The role of excess insulin in negatively affecting eicosanoid balance also explained why excess insulin was highly associated with heart disease. It wasn't that insulin was a cause, but that it drove the metabolism of essential fatty acids to make more arachidonic acid, and therefore more "bad" eicosanoids. The more "bad" eicosanoids you make, the more likely you will promote platelet aggregation and increased vasoconstriction, the underlying factors for a heart attack.

I knew the only way to control insulin required controlling the protein-to-carbohydrate ratio at every meal. Again I was confronted by what the optimal ratio of protein-to-carbohydrate ratio should be? A good beginning was to attempt to estimate the ratio of protein-to-carbohydrate ratio consumed by neo-Paleolithic man some 10-40,000 years ago, since our genes haven't changed that much since then.

Fortunately, such an estimate did exist in research published in an 1985 issue of The New England Journal of Medicine. Using anthropological data and comparing a large number of existing hunter-gatherer tribes, these researchers estimated the average protein-to-carbohydrate ratio in neo-Paleolithic diets to be approximately 3 grams of protein for every 4 grams of carbohydrate, or a protein-to-carbohydrate ratio of 0.75. Using this research as a starting point, I began developing a diet that would control the protein-to-carbohydrate ratio in a range between 0.5 and 1.0 at every meal so that the balance of insulin and glucagon would be maintained from meal to meal. This is the foundation of the insulin control component of my dietary recommendations.

Thus, my dietary program controls both the ratio of long-chain Omega-3 fatty acids to Omega-6 fatty acids as well as the balance of protein-to-carbohydrate at every meal while restricting total calories. This dietary strategy maintains the dynamic balance of eicosanoids by controlling the levels of the actual precursors and the hormones responsible for activating the critical enzymes in essential fatty acid metabolism. By keeping the balance of eicosanoid precursors in an appropriate zone (after all, you need some "bad" eicosanoids to survive), you also control the information flow of your Biological Internet. Control that flow and avoid hormonal miscommunication, and you have begun to reverse the aging process.

The development of chronic diseases (heart disease, diabetes, cancer, and arthritis) associated with aging does not occur overnight but is the result of constant hormonal insults to your body. But by the time they do appear, significant (and potentially irreversible) organ damage may have occurred. So if eicosanoids act as master hormones that control this complex hormonal communication system, is there some way we can continue to monitor and fine-tune this ultimate mechanism of aging before chronic disease conditions appear? If so, then you could tell when you are moving out of the appropriate eicosanoid zone and then take immediate dietary steps to restore that balance? There are very few direct diagnostic tests for eicosanoids. However, the ratio of AA/EPA will provide a remarkably good insight into your eicosanoid status. More importantly, this is a blood parameter that can be changed rapidly within 30 days.

Now... questions?

more info - http://www.itmonline.org/arts/lox.htm


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## Captain Hero (Jun 13, 2004)

Interesting read Chef  Easy to read might have to go over it one more time though as its a fair bit to take in. I do have one question though, do you think a cure to Aids and other diseases lies in eicosanoids? you said that injecting a corticosteroid would make a healthy persons immune system like that of someone with Aids so eicosanoids must be where a cure for it lies right? Or is it not as simple as that?


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## ChefX (Jan 10, 2005)

Cap its not my writing, it's Barry Sears. I would never write that clear and typo free. LOL I do still support his writings and reasons even though I disagree on how it all came about. Also i'm anti soy where he is very pro soy. otherwise we work the same side of the fence.

Its not that simple Cap. I wish it was. But right now it looks like eicasanoids are the future of all medicine. As far as treatment of aids and such, best bet is gene therapy coupled with the new delivery systems (beleive it or not the delivery systems rely on eicasanoids and thats the secret. Lorian you should take the hint from this concerning on supplement company we talked about before)

I was in school at the time this all came about, my specialty was drug delivery through nutritional modalities and as such I took a hard interest in this. Beleive it or not the Soviets were light years ahead of everyone else in this stuff and I'll let you know many times when accused of drugs their guys were not on the, they just had things dialed in right.

Anyway you look at it, the closer you get eicasanoids to the ideal level the better your health, better you live and the better the performance. As for bodybuilding it means larger natural; people but drugs throw a wrench into it, still balancing everything else means far les drugs to get the same results. This should show you why I hate the monster massive drug cycles people waste their lives on by being lazy in all other areas.)


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## Captain Hero (Jun 13, 2004)

ChefX said:


> Cap its not my writing, it's Barry Sears. I would never write that clear and typo free. LOL I do still support his writings and reasons even though I disagree on how it all came about. Also i'm anti soy where he is very pro soy. otherwise we work the same side of the fence.
> 
> Its not that simple Cap. I wish it was. But right now it looks like eicasanoids are the future of all medicine. As far as treatment of aids and such, best bet is gene therapy coupled with the new delivery systems (beleive it or not the delivery systems rely on eicasanoids and thats the secret. Lorian you should take the hint from this concerning on supplement company we talked about before)
> 
> ...


LOL i did notice it was very typo free  Damn always comes back to Soviet research, why did the Soviet Union have to crumble :boohoo:Just think what else could have been learnt had it still been around today. Ah well im investing in some of theyre training books anyways. I agree with you on the monster massive cycles chef! Classic look like Steve Reeves/Reg Park all the way!


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## ChefX (Jan 10, 2005)

The soviet union crumbled because it was wrong. It's not that they were better at all, it's just that I had access to stuff they did more than others hence I use(d) it to my advantage. It's no better, just different. Of course it doesn't hurt that lying did the scientist no good so the honesty was better (in the private stuff, not the public prooaganda publishings) also the fact they used humans in studies instead of animals and paper makes a good difference too (albeit illegal and wrong)


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## Great White (Apr 4, 2003)

Thanks for the Info ChefX and SportsDR

So basically i was right, its just a load of [email protected]


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## ChefX (Jan 10, 2005)

Paul Govier said:


> Thanks for the Info ChefX and SportsDR
> 
> So basically i was right, its just a load of [email protected]


yep


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## hackskii (Jul 27, 2003)

Bumping this for myself.

Also I am just reading on AA and too much is not good.

PG2 or prostaglandin2 causes inflimation

PG1 and PG3 decrease inflimation.

Those fish oils chef was talking about are awesome.

Getting alot of AA in the body will upset the ballance of Omega 3 to Omega 6 fatty acids in the body.

Was reading today on GLA and CLA (they come from Omega 6 fatty acid), they are great for fat loss but if you take these you are forced to supplement Omega 3's or you will end up in trouble.


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## hackskii (Jul 27, 2003)

Bumping this for good reading.

Found another site that was promoting a product.

Seems that the latest and greatest is re-packaged, re-done and will take millions off of advertisement to make a bundle.

Read this and tell me that you would not buy it

http://www.molecularnutrition.net/

Then read above what Chef has to say, this is funny.

Paul Originally posted this article.


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## cheapuksupplements.com (Sep 15, 2004)

Havent read a lot into this product, but recently saw a load of testing on bb.com Molecular did and the results were very good. Many testers gained a decent amount of muscle and lost fat as well. I dont think there was one "bad" test.


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## 3752 (Jan 7, 2005)

yea since i decided to stop using AAS i have been looking into this shame you can only get it from BB.com


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## cheapuksupplements.com (Sep 15, 2004)

Pscarb said:


> yea since i decided to stop using AAS i have been looking into this shame you can only get it from BB.com


We stock it, Molecular Nutrition X-Factor. Although we are out of it at the moment, but will have more in soon. We have been talking to Molecular and may also be running some testing on our board at some stage.


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## hackskii (Jul 27, 2003)

Bumping this post as some feel X Factor is a good thing.

I would not take this stuff if you payed me.


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## Tinytom (Sep 16, 2005)

I tried it and got not a lot off it.

Personally I wopuld prefer to spend the cash on gear as the lipid problems are the same with both.


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## Tatyana (Jan 29, 2006)

Paul Govier said:


> *MORE PAIN, MORE GAIN*
> 
> *Ok some scientific literacy here. EXACTLY how muscular growth occurs is not known, and thus far there are no direct links between pain and gain. As far as science has discovered, the prostaglandins are cytokines (like hormones from the cells), that modulate pain receptors, no more, no less. *
> 
> ...


Yes, it is a bit scary what people can try and prove in the supplement industry.

The words 'long term longitudinal study' or 'meta-analysis' need to be present in the papers. This indicates that research has taken place on tens of thousands of people, over a significant amount of time.

Otherwise, a study of 24 young men is like saying, my neighbour developed breast cancer and she ate grapes, so if I eat grapes, I will get breast cancer.

I would bet dollars to donuts that if you looked at the original paper the researchers would have put in the discussion, 'while these results are interesting, further research has to be performed to determine a causitive link'.

I am on a roll, at least half of what you do in a Jedi Masters in science is to CRITICALLY REVIEW scientific papers to find errors in their scientific methodology or statistics.

x

x

x

T


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## hackskii (Jul 27, 2003)

Bump.

I just want to add this is something that is in most of everyones diet and not needed to supplement.

If it is in all animal protein, eggs and shell fish why supplement this?

If it has such a strong exertion on inflammation why supplement?

After all, PG2 is a pro-inflammatory prostaglandin and is associated with many not so good health conciquences even cancer.

Why supplement something that most get enough of?

The conciquences are not good.

Rats have depression when excessive AA is in the brain, why not DHA instead where this is said to be an anti-alzheimers fatty acid?

Again, AA is a pro-inflammatory and from all I have read is or should be reduced in the body.

The eskimos probably were defficient in this supplement but suffered no ill effects.

Why add something that is totally prevelant in the bodybuilders diet?

If anything moreso than most supplements?

Where do you draw the line in more is better?

At what point would this become a benefit of deminishing returns?

Id steer clear of this supp as I feel it is a wolf in sheep's clothing, regardless of what the studies say.

After all it is a Omega 6 fatty acid and as we all know this is abundant in our diets and for the most part Omega-3 should be supplemented not 6.

Thanks Tat, I will read more tomorrow.

I love these debates actually.


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## hackskii (Jul 27, 2003)

I really do have alot of heartburn with AA and I feel it should be banned from the supplement standpoint.

Many are making alot of money on the studies and the supplement on X Factor but I for one feel this is something that is a marketing hype, A dangerous one at that.

From everything I have ever read AA should be reduced in the body not elivated.

Call me old school, call me cautious......

*This stuff is poision*.....Well in the stand point of supplementing it into a diet already rich in it...


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## Tatyana (Jan 29, 2006)

hackskii said:


> Bump.
> 
> I just want to add this is something that is in most of everyones diet and not needed to supplement.
> 
> ...


Ok I also wanted to bring out some interesting research I just came across.

I am NOT going to type out the entire paper, and I don't think I have access to the full article, I photocopied this paper from a journal for my Jedi Master's course work.

Annals of Clinical Biochemistry 2006, 43: 252-256

High sensitivity C-reactive protein (CRP) and cardiovascular disease: an association built on unstable foundations?

Abstract

Some authorities proposed potential inclusion of CRP in risk factor stratification (for cardiovascular disease or CVD). However, more recent evidence in the last two years from larger studies suggest that CRP concentrations are only aro9und as half as predictive for vascular events as suggested in earlier reports.

The short-term variability of CRP is also problematic for risk factor screening.

Therefore, the current focus in clinical practice should remain on established risk factors (eg smoking, lipids and blood pressure), both to determine coronary heart disease risk and to reduce it.

Conclusion

Evidence in the last two years suggests that measuring hsCRP yeilds little additional predictive value to current CHD risk prediction scores or charts and other evidence summarised in Table 1 questions its proposed causal role in atherogenesis (formation of athersclerotic plaques or the blocking of coronary arteries and veins).

This is good news for bodybuilders as most have elevated levels of CRP.

Inflammation is NOT a bad thing, it is what our bodies do, it is part of the primary or innate immune response. I get some people do not take care of their bodies, however, trying to completely suppress the immune/inflammation response would also suppress the immune system.

x

x

x

T


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## hackskii (Jul 27, 2003)

Im on another board posting against the manufacturers

Boy are they defensive.

This is such an interesting debate, now they want me to post some clinical studies that suggest we are taking in too much Omega 6's.

They are throwing everthing at me and I am holding fast.

I have like 4 or 5 posts on that board all on the same thread

I think someone put under my user name *Public Enemy #1*

I am actually waiting to see me either banned or my posts edited.

They are defending their X Factor so hard you can tell they are selling the stuff and I am deffo not good for business.

I feel like digging for a day and getting all the negatives of AA and blasting them with info.

It is pretty fun actually...heeee heeeee

Two threads on two boards at the same time.

I even took some of Tats stuff and copied and pasted....LMAO, thanks Tat.

I do like how you can read those peer reviews, those do my head in pretty quick.

Cheers for the info Tat


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## BSF James (Sep 29, 2003)

Do you have the link to the discussion Hackskii?

We sell X Factor. I tried it myself and seemed to be getting quite good results if I'm honest until I had to take a few weeks off from training, but nothing spectactular - not the results I've read of on US boards anyhow. Our sponsored athlete tried it as well and he was fairly positive, but again - he wasnt gaining 20lbs or anything like some people claim on the boards, just some solid strength gains.

Realistically I dont think AA in the dose in that product should cause any health problems, but I'm not a doctor so will defer on that.

As you mention diet and how AA is in eggs, I'm sure I remember reading part of Molecular's advert that suggested the reason old-time bodybuilders did so well without drugs was because they ate lots of steak and eggs which provided them with high doses of AA. Did you see that? Bit of a stretch that one I think. Although something to think about I suppose.

The science sounds great on paper, but I'm not sure how well it actually works in practice. Yes you're increasing the autoimmune response and inflammation by taking in extra AA and the prostaglandins may well exert a positive effect on muscle growth, but conversely doesnt increasing inflammation also increase muscle breakdown and decrease recovery?

Interestingly, AST who we distribute in the UK for, have brought out a product that works in the exact opposite way - its fish oil based with aminos and decreases inflammation and protein breakdown whilst increasing recovery. I'm yet to try this one, but it will be good to see how it compares to X Factor.

It all seems to be conflicting - should we increase inflammation or reduce it? Common sense would say to me to reduce it, but in all honesty I've not researched it enough to make a decision.

On a side note, increased prostaglandins in the scalp inrease the rate of hair loss in those predisposed to it, so I wouldnt recommend X Factor if you are receding whilst conversely high omega 3 products like the AST one may be a good addition to your diet if you are 'follically challenged'.


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## hackskii (Jul 27, 2003)

I have to warn you I am a mad man on there debating many of the dudes that are sponcering the supplement or even manufacturing it.

They are pulling a bunch of studies out.

But to be honest I dont buy their load of BS, just good ol practical sense is all that is needed.

I am very hard on them

Serves them right for selling something that is counterproductive to good heatlh.

http://www.avantlabs.com/main.php?pageID=97

Check out how hard I am on them


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