We get almost 500mg of AA a day, so why should we keep GLA at 2mg/day or less? Even if the 2mg are converted into AA, what does it represent in comparison to 500mg? Alos, don't we produce way more than 2mg of GLA a day though the conversion of LA (linoleic acid) by D5D? Please, explain that to me.

Are these sucha stupid questions and can I find the answers in Dr Sears' book?

[quote:f07315b79b]Alos, don't we produce way more than 2mg of GLA a day though the conversion of LA (linoleic acid) by D5D? [/quote:f07315b79b] FYI --D[i:f07315b79b]6[/i:f07315b79b]D desaturates LA to GLA. See http://www.zonehome.com/zlibstar.htm for GLA production rates and GLA supplementation. The 1996 GLA articles by Michael Kurilla.

Scott, That was a typo, I was indeed talking about the D6D. It doesn't answer my questions though. Could you answer them now? Thank you, ZA

The issue here is that excess GLA can spill over into more AA which is what we are trying to prevent. EPA helps to suppress the activity of D5D to prevent AA and bad eicosanoid production. If i remember correctly GLA has the ability to suppress D6D and increase AA production, which is how excess GLA can spill over into AA. That is why the restriction of GLA intake is desirable, and can be fulfilled with a bout 2 bowls of slow cooked oatmeal a week. hope that helps

Thank you but you didn't answer any of the 3 questions. Here there're again: 1) We get almost 500mg of AA a day, so why should we keep GLA at 2mg/day or less? 2) Even if the 2mg are converted into AA, what does it represent in comparison to 500mg? 3) Also, don't we produce way more than 2mg of GLA a day though the conversion of LA (linoleic acid) by D6D? Actually, M. Kurilla reports 250 to 1000mg of GLA/day according to a published article! Again, what's 2mg in comparison with what the body produces every day?

[quote:0d765239fc="zonadept"] 1) We get almost 500mg of AA a day, so why should we keep GLA at 2mg/day or less?[ 2) Even if the 2mg are converted into AA, what does it represent in comparison to 500mg? 3) Also, don't we produce way more than 2mg of GLA a day though the conversion of LA (linoleic acid) by D6D? Actually, M. Kurilla reports 250 to 1000mg of GLA/day according to a published article! Again, what's 2mg in comparison with what the body produces every day?[/quote:0d765239fc] A calorie restricted program like the Zone would increase the activity of the D6D enzyme close to 300%-increasing the rate of GLA production further. Your points makes for interesting discussion which is why I highlighted Kurillas writing. Not everyone seems to agree. I suspect that the Zone assumes you have already incorporated GLA and sufficient EPA to account for the rate of linoleic desaturation and dietary AA (which is minimized with the Zone). Thus it onyly takes small amounts of GLA to tip the scales since only about 1mg of AA is used for eicosanoid production. I believe Dennis experiences it quite readily.

I'm not sure how you figure we get 500 mg of AA per day. Where does that figure come from? I believe GLA can go down either the D5D or D6D path. I suspect the threshold amount of GLA that can tip the scales back toward AA production is not consistent, but more likely tied to a combination of dietary factors. Interesting that calorie restriction increases D6D activity... I hadn't heard that. That being said, i expect that the amount of GLA intake may not be as critical as it would be without PGFO, and that this combined with calorie restriction would increase GLA tolerance even further. I do know Dr. Sears talks about this in his book Omega RX Zone. He described an experiment he did with some willing participants in which he discovered that excess GLA was going down the wrong path. If I remember correctly it had something to do with GLA suppressing D6D activity. I believe this event was what turned him toward using EPA to suppress D5D activity. I'm not sure there are absolute numbers to answer your questions with but the I think the important thing is that the 2mg per day of GLA is what is needed that doesn't get converted to AA. I've seen GLA capsules that contained much larger doses of GLA and i think those are what you really have to be careful about. another 2 mg of AA isn't going to tip the scales... another 500mg of GLA converted to AA because of D6D suppression might. To the 3rd question... i believe you are correct, we produce GLA via the D6D path but I believe it acts as its own rate limiter so the more it produces the more D6D activity is suppressed, which is why EPA has become so much more important a supplement than GLA. I raised that question myself on the forum some time ago regarding whether GLA supplementation was even necessary any longer, provided you are taking a PGFO supplement wich suppresses D5D activity in favor of D6D activity. Of course that fact in and of itself may also point to why Dr. Sears recommends such a small limit on GLA... because your body is producing what it needs due to the affect of EPA on D5D. BartC

[quote:11ce359004="bchandler"] I believe GLA can go down either the D5D or D6D path. [/quote:11ce359004] Just to clarify the omega-6 pathway: D6D desaturates (adds a double bond to) linoleic acid (18:2n-6) to yield GLA.(18:3n-6) GLA elongates to DLGA (20:3n-6). DGLA is the precursor to the series-1 eicosanoids. D5D desaturates (adds a double bond to) DGLA to yield AA (20:4n-6) and the series-2 eicosanoids. [quote:11ce359004]Interesting that calorie restriction increases D6D activity... I hadn't heard that. That being said, i expect that the amount of GLA intake may not be as critical as it would be without PGFO, and that this combined with calorie restriction would increase GLA tolerance even further.[/quote:11ce359004] That depends. Because both omega-3s and omega-6 utilize the same desaturase enzymes, too much omega-3s can inhibt D6D and GLA production from linoleic acid. [quote:11ce359004]I do know Dr. Sears talks about this in his book Omega RX Zone. He described an experiment he did with some willing participants in which he discovered that excess GLA was going down the wrong path. If I remember correctly it had something to do with GLA suppressing D6D activity. I believe this event was what turned him toward using EPA to suppress D5D activity.[/quote:11ce359004] Not necessarily the [i:11ce359004]wrong[/i:11ce359004] path. DGLA was being desaturated towards AA and the series-2 eicosanoids as opposed to the series-1 eicosanoids via increased activity of D5D. [quote:11ce359004]regarding whether GLA supplementation was even necessary any longer, provided you are taking a PGFO supplement wich suppresses D5D activity in favor of D6D activity. [/quote:11ce359004] Although inhibition of D5D can increase the levels of DGLA (provided adequate GLA is the pipeline), high levels of EPA can suppress the D6D enzyme needed to desaturate linoleic acid to GLA. The use of omega-3's may require more GLA.

[quote:8ae49473d9="Scott"]Although inhibition of D5D can increase the levels of DGLA (provided adequate GLA is the pipeline), high levels of EPA can suppress the D6D enzyme needed to desaturate linoleic acid to GLA. The use of omega-3's may require more GLA.[/quote:8ae49473d9] Really? I thought EPA was a rate limiter for D5D not D6D. I thought that was the whole point of EPA supplementation. To promote healthy cell membranes and suppress D5D to reduce AA production. I didn't recall and couldn't find anything in the Omega RX zone to indicate EPA suppressed D6D. Iwas also under the impression that GLA was the D6D rate limiter.... is that totally wrong? I had this picture in my head of this nicely balanced self limiting system where EPA and GLA worked together to balance auto-rate limit over production of eicosanoids down either pathway.... am i completely off base? Guess i might have to re read that book...lol

[quote:911e555403="bchandler"] Really? I thought EPA was a rate limiter for D5D not D6D. I thought that was the whole point of EPA supplementation. To promote healthy cell membranes and suppress D5D to reduce AA production. I didn't recall and couldn't find anything in the Omega RX zone to indicate EPA suppressed D6D. Iwas also under the impression that GLA was the D6D rate limiter.... is that totally wrong?[/quote:911e555403] You are not wrong. EPA does suppress D5D and reduce AA formation from DGLA. It also competes with AA for the same enzymes (COX) that produce series-2 (AA) and series-3 (EPA) eicosanoids. In excess, however, omega-3s can inhibit the D6D enzyme as it is used in the conversion of EPA to DHA. Page 243 and 247 of the OmegaRXZone: [i:911e555403]Long chain omega-3 fatty acids such as DHA act as feedback inhibitors of the enzyme [/i:911e555403][D6D] [i:911e555403]DHA acts as a feedback inhibitor of the delta-6-desaturase enzyme...[/i:911e555403] [quote:911e555403]I had this picture in my head of this nicely balanced self limiting system where EPA and GLA worked together to balance auto-rate limit over production of eicosanoids down either pathway.... am i completely off base?[/quote:911e555403] You're picture is accurate (balancing GLA and EPA to balance eicosanoids), I just think you have D6D in the wrong place. What controls GLA-->DGLA towards more "good" eicosanoids and fewer "bad" is calorie restriction to increase D6D activity that desaturates LA to GLA, small amounts of GLA to make-up for any decrease in D6D activity due to aging, alcohol intake, and other factors and lowering the activity of D5D that would desaturate DLGA to AA by lowering insulin and getting adequate EPA. The above strategies increase the amount of DGLA relative to AA, and hence series-1 eicosanoids relative to series-2. [quote:911e555403] Guess i might have to re read that book...lol[/quote:911e555403] Still referring to it...

OK, so i did have it right... and i was expecting EPA to inhibit D5D. so let me see if i got this right... DHA is retroconverted to EPA by D6D (I think you had that backwards), so too much DHA will take up time in the enzyme pathway that could have been used to make good eicosanoids and precursors, and in this way limits D6D. So its the DHA that can suppress D6D, not EPA? is that right?

[quote:2f373c668e="bchandler"]so let me see if i got this right... DHA is retroconverted to EPA by D6D (I think you had that backwards), so too much DHA will take up time in the enzyme pathway that could have been used to make good eicosanoids and precursors, and in this way limits D6D.[/quote:2f373c668e] Hold-up--I mispoke. EPA is [i:2f373c668e]elongated and desaturated [/i:2f373c668e]to DHA via D6D, and DHA can be [i:2f373c668e]retroconverted[/i:2f373c668e] to EPA. Thus, EPA is used to make DHA via the D6D enzyme. Thus DHA is a [i:2f373c668e]feedback[/i:2f373c668e] inhibitor of D6D. As more DHA is produced, the activity of the enzyme is inhibited. EPA would also affect D6D because its elongase product (C24:5) would be a [i:2f373c668e]competitive[/i:2f373c668e] inhibitor. Here's the pathway from page 246, appendix D: C20:5 (EPA) C22:5 C24:5 [i:2f373c668e]delta-6-desaturase[/i:2f373c668e] C24:6 peroxisomal oxidation C22:6 (DHA) peroxisomal oxidation C20:5 (EPA) [quote:2f373c668e] So its the DHA that can suppress D6D, not EPA? is that right?[/quote:2f373c668e] I would say both. But you're right, the fact that these omega-3s use the D6D enzyme means less activity for the omega-6 pathway and the "good" eicosanoids.

[quote:ca7e3938f2="bchandler"]I'm not sure how you figure we get 500 mg of AA per day. Where does that figure come from? BartC[/quote:ca7e3938f2] I did a simple calculation based on USDA figures. "The average western diet is estimated to provide about 200 - 400 mg of AA per day (Adam, 1992). " So I still don't understand why we should worry so much about GLA. Even 50mg daily wouldn't make much of a diffeence in comparison to say 300mg of AA even in the conversion rate was 100% Also "GLA is an unusual fatty acid that is rare to find naturally occurring in significant amounts (pure chicken fat has 21 mg in 3.5 ounces, while the same size of lean chicken meat has only 3.8 mg)." Read my post "GLA is everywhere" too in the "Health" section of this forum.

OK, so the USDA figures are going to be skewed to their food pyramid, or to what average americans actually eat. You... eating in the Zone won't be or shouldn't be eating all the things that the "average" american does, and as a result will likely get much less AA than the "Average" american

This subject has also been a point of interest for me in the last several years. Last week, while at the bookstore to purchase my copy of "The Anti Inflammation Zone", I noticed another book, "Inflammation Nation" by Floyd Chilton. The book caught my eye because I have followed Dr. Chilton's research on using GLA and EPA to treat asthma, which is a quite similar condition to my own difficulties with severe seasonal allergies. Chilton pushes essentially the same concepts as the zone (including insulin control), but with one notable difference - he recommends increased GLA supplementation and lower dose EPA supplementation compared to Dr. Sears's recommendations (and not just for asthmatics, but for the general population as well). He also emphasizes reduced preformed AA consumption to go along with his supplementation recommendations. In my own experience, I have found increased GLA supplementation (up to 440mg/day) to be very beneficial. Using GLA supplementation at that level along with high dose fish oil has given me considerably better results than high dose fish oil alone. So much so, in fact, that I have been able to completely eliminate allergy symptoms for the last couple of seasons. Still, I worry about the spillover effect since Dr. Sears seems to emphasize it so much. Based on my experience, I speculate that I may have a reduced D6D activity (even when following the zone dietary principals) - which may explain the discrepancy between my experience and zone theory. As Scott mentioned, Dr Kurilla and others (including Horrobin) have promoted larger amounts of GLA supplementation - so I too think it remains a controversial issue and one that I would love to see more data and information on. I also wonder about the AA/EPA ratio as an absolute measure of the inflammatory state when it does does take into consideration DGLA levels, which are know have strong anti-inflamatory effects. I apologize if I provided more questions than answers. I, like zoneadept, am searching for more information on this subject. I appreciate your comments regarding this topic. Thanks! Terry

[quote:81c195e937="zonelifter"] Using GLA supplementation at that level along with high dose fish oil has given me considerably better results than high dose fish oil alone. So much so, in fact, that I have been able to completely eliminate allergy symptoms for the last couple of seasons. Still, I worry about the spillover effect since Dr. Sears seems to emphasize it so much. Based on my experience, I speculate that I may have a reduced D6D activity (even when following the zone dietary principals) - which may explain the discrepancy between my experience and zone theory.[/quote:81c195e937] Thanks for your informative post. Just curious as to how much fish oil you are taking. As mentioned previously, it can have the effect of reducing the amount of GLA that is produced necessitating additional GLA (or reduced omega-3). However, an inherent deficiency in D6D activity may be cause as well. The synergistics effects of EPA and GLA together, rather than either alone contribute to the increase production of series-1 eicosanoids. Re the amounts that David Horrobin would advocate, I wonder whether the differences in recommendations rest with the calorie restriction aspects of the Zone. Calorie restriction would increase the activity of the delta-6-desaturase enzyme which would lower the requirements for supplemental GLA. [quote:81c195e937] <<I also wonder about the AA/EPA ratio as an absolute measure of the inflammatory state when it does does take into consideration DGLA levels, which are know have strong anti-inflamatory effects.[/quote:81c195e937] EPA would increase the amount of DGLA relative to AA thus AA/EPA would seem to be a surrogate marker for DGLA/AA. The DGLA/AA ratio has been a fundamental tenet of the Zone, however I have seen much more published literature on the AA/EPA ratio as opposed to the DGLA/AA when it comes to assessing disease risk. That may be why AA/EPA is the current measure. It does seem that a DGLA/AA score would give you a better picture of your GLA status. Interestingy, some researchers look at AA/DHA as well.

[quote:8a9d311698="zonadept"] I did a simple calculation based on USDA figures. "The average western diet is estimated to provide about 200 - 400 mg of AA per day (Adam, 1992). " [/quote:8a9d311698] Keep in mind that the average westerner has an AA/EPA ratio of around 12, and currently supports the billion dollar market of COX, LOX, and other drugs that inhibit the enzymes or act as receptor antagonists in the arachidonic acid cascade. Celebrex, Vioxx, Zafirlukast (Accolate), Montelukast (Singulair), aspririn, ibuprofen (motrin, advil) naproxen, indomethacin--and on and on...

[quote:ee2dfc501b="bchandler"]You... eating in the Zone won't be or shouldn't be eating all the things that the "average" american does, and as a result will likely get much less AA than the "Average" american[/quote:ee2dfc501b] Well, I eat fish and meat. Even lean cuts are rich in AA.

SCott, Have a look at the AA content of common food: http://www.nutritiondata.com/foods-...00-w5.html If the link doesn't work, do the search yourself.

zoneadept - Thanks for the link. I haven't had a chance to look at it in detail, but it looks to be a very valuable source of AA content data. Do you know if it uses the USDA database for its data source? Or does it use data derived from testing independant from the USDA's testing? Scott - Thanks for your comments. For the last 2 allergy seasons (Spring and Fall 2004), I have used 2400mg EPA and 1200mg DHA (6 capsules) daily to go along with the 440mg of GLA to get complete relief from allergy symptoms. My first experience with high dose fish oil was in 2003 immediately after I read the "OmegaRx Zone." I immediately began using 7.5 g of EPA & DHA (1 tablespoon per day of the liquid OmegaRx). During that season, my allergy symptoms were dramatically reduced (though not completely relieved). Still, I was quite happy with the results until I began to experience extreme fatigue about 6 weeks after beginning supplementation. After doing some research (primarily the Holub papers), I suspected that low DGLA levels might be the cause, so I bought some borage oil to try. I experienced a dramatic improvement in my fatigue after my very first borage oil dose (220mg GLA). That experience was very consistent with your comments that high dose fish oil can reduce GLA production as well as with Holub's research that indicated that 4g of EPA/DHA per day dramatically reduced DGLA levels. Consistent with your comments, I am contemplating reducing fish oil supplementation levels further. I am curious to know if I can get the same results with the reduced EPA/DHA supplementation. Perhaps I can reduce my GLA supplementation accordingly and still get the same results. The next allergy season isn't for several months, so I have a while before I can evaluate it. I'm also keeping my eye on the advancement of blood testing for AA, EPA, DHA, & DGLA levels. Ideally, I would like to do that on a regular basis if the cost and ease of performance continue to improve. I also use the eiconsanoid status report, but experience has taught me that a good eisosanoid status report does not necessarily give me good allergy symptom relief once the allergy season hits - so I've come to rely on my allergy symptom relief as my primary indicator of my zone & fatty acid level status. Thanks again for your comments. I appreciate your thoughts. Terry

[quote:9a91d39f76="zonadept"]SCott, Have a look at the AA content of common food: http://www.nutritiondata.com/foods-...00-w5.html If the link doesn't work, do the search yourself.[/quote:9a91d39f76] First--thanks for the link--pretty neat setup. Second-the amounts on that table (highest in 20:4) were in 6-block portions--so I had to prorate to one block increments. In choosing a few of what appeared to be [i:9a91d39f76]favorable[/i:9a91d39f76] choices (chicken/turkey)--a lot of unfavorables in the list-- it looks as if it comes to between 30-40mg AA per protein block. So let's say you have two meals per day that include these foods. At 8 blocks (average male for two meals) you'd get close to 280mg. Next you fine tune with EPA and GLA such that along with your average dietary intake of AA coupled with your protein-carb ratio and its impact on D5D, you find your self checking off more positive marks on the ESR. Or you are more exact and get an AA/EPA test. It seems to me that since the amount of EPA and GLA arrived at was in conjunction with your current dietary AA intake--dietary sources become irrelevant provided you are consistent with your average AA intake. What IS relevant is the amount of GLA it takes to begin an [i:9a91d39f76]accumulation[/i:9a91d39f76] of AA in the phospholipids. Or if you happen to take in more AA on a certain day. There also may be an inherent difference in how the body metabolizes dietary sources of AA vs. AA derived from GLA in the cellular membranes. Is the excess dietary AA taken in on a given day (since your EPA/GLA was derived along with an average AA intake) incorporated into the cellular membranes to the same extent as the desaturation of DGLA. Ultimately, one would think that as long as DGLA rises higher relative to any increase in AA, you should be ok.

[quote:aae8ffddcd="zonelifter"]After doing some research (primarily the Holub papers), I suspected that low DGLA levels might be the cause, so I bought some borage oil to try. I experienced a dramatic improvement in my fatigue after my very first borage oil dose (220mg GLA). That experience was very consistent with your comments that high dose fish oil can reduce GLA production as well as with Holub's research that indicated that 4g of EPA/DHA per day dramatically reduced DGLA levels. Consistent with your comments, I am contemplating reducing fish oil supplementation levels further. I am curious to know if I can get the same results with the reduced EPA/DHA supplementation. Perhaps I can reduce my GLA supplementation accordingly and still get the same results. [/quote:aae8ffddcd] I am very interested in your results. Further to your experience, Holub published a paper in 2003 which looked at 4g EPA/DHA coupled with 0gGLA, 1gGLA, 2gGLA, and 4gGLA. The 4:2 group experienced a decrease in LDL. Prostaglandin E1 is known to increase the receptor binding for LDL, so it seems that a 4:2 ratio of EPA/DHA to GLA provided the greatest increase in "good" eicosanoids. EPA/DHA alone did not increase DGLA signifcantly, and 4:4 may have increased AA more so than the rise in DGLA. Now these were women probably on a standard western diet so the relative of amounts needed would change following Zone principles (most likely less GLA given increased enzyme activity), but it does highlight the importance of finding that optimal GLA/EPA balance. Laidlaw M, Holub BJ [i:aae8ffddcd]"Effects of supplementation with fish oil-derived n-3 fatty acids and gamma-linolenic acid on circulating plasma lipids and fatty acid profiles in women." [/i:aae8ffddcd]American Journal of Clinical Nutition 2003 Jan;77(1):37-42

[quote:8e1ee2e216="zonelifter"]Still, I was quite happy with the results until I began to experience extreme fatigue about 6 weeks after beginning supplementation. After doing some research (primarily the Holub papers), I suspected that low DGLA levels might be the cause, so I bought some borage oil to try. I experienced a dramatic improvement in my fatigue after my very first borage oil dose (220mg GLA). [/quote:8e1ee2e216] I'm curious whether the extra GLA eliminated the fatigue due to higher DGLA, or what ultimately would be come more AA. Too many vasodilating (ie "good") eicocanoids that can occur from higher omega-3s can promote electrolyte loss and induce fatigue. [quote:8e1ee2e216] I'm also keeping my eye on the advancement of blood testing for AA, EPA, DHA, & DGLA levels. Ideally, I would like to do that on a regular basis if the cost and ease of performance continue to improve. [/quote:8e1ee2e216] When my wife had the AA/EPA test, I asked for a breakdown of all the fatty acids and was able to get numbers for DGLA, GLA, DHA etc. Unfortunately, I havn't see much data on an optimal serum DGLA/AA ratio

[quote:4d4ae3bddd="zonelifter"]In my own experience, I have found increased GLA supplementation (up to 440mg/day) to be very beneficial. Using GLA supplementation at that level along with high dose fish oil has given me considerably better results than high dose fish oil alone. So much so, in fact, that I have been able to completely eliminate allergy symptoms for the last couple of seasons. Still, I worry about the spillover effect since Dr. Sears seems to emphasize it so much. Based on my experience, I speculate that I may have a reduced D6D activity (even when following the zone dietary principals) - which may explain the discrepancy between my experience and zone theory.[/quote:4d4ae3bddd] Quite interesting. I had the opposite experience with my seasonal allergies and fatigue. I had been taking high dose GLA for years to no benefit. When I started the Zone diet, I started on high dose PGFO. After feeling good for a week, I would become fatigued. I found that I had to keep increasing my PGFO and decreasing dietary sources of GLA to continue to feel better. Finally with 27g of PGFO and minimal GLA, my allergy symptoms have virtually vanished and I never feel fatigued now.