Post by Sal on Sept 5, 2013 17:13:03 GMT
Year | Title | Authors | Country |
2008 | Control of salicylate intolerance with fish oils | Friedmann et al | UK |
Control of salicylate intolerance with fish oils.
Healy E, Newell L, Howarth P, Friedmann PS.
Source-Dermatopharmacology Unit, Southampton University Hospitals Trust, Southampton SO16 6YD, UK.
We report three patients with disabling salicylate-induced intolerance who experienced abrogation of symptoms following dietary supplementation with omega-3 polyunsaturated fatty acids (PUFAs). All three patients experienced severe urticaria, asthma requiring systemic steroid therapy and anaphylactic reactions. After dietary supplementation with 10 g daily of fish oils rich in omega-3 PUFAs for 6-8 weeks all three experienced complete or virtually complete resolution of symptoms allowing discontinuation of systemic corticosteroid therapy. Symptoms relapsed after dose reduction. Fish oil appears a safe and effective treatment for this difficult and often serious condition.
2009 Interview with Peter Friedmann, one of the researchers
Kirk Hamilton: Can you please share with us your educational background
and current position?
Peter S. Friedmann: I trained in Medicine at Cambridge University and University College Hospital London. I did further training in immunology and dermatology. I was Professor of Dermatology at Liverpool University from 1990 -1997 and Professor of Dermatology in the University of
Southampton from 1998 until 2007.
KH: What got you interested in studying the role of fish oilsupplementation and salicylate intolerance?
PSF: Twelve years ago I first got involved in studying whether fish oils rich in omega 3 fatty acids were able to protect against tissue damage caused by free radicals. The source of free radicals we were interested in was ultraviolet light. We showed that dietary supplementation with omega 3 conferred significant protection against many of the damaging effects of UV light, the most obvious of which was the sunburn effect. The main chemicals that are responsible for the redness of sunburn are prostaglandins , particularly prostaglandin E2 (PGE2). We showed that the omega 3 soaked up the free radicals and there was much less release of PGE2 with much less sunburn. It is now also well known that the cell membrane fat (lipid) that is released as a precursor of PGE2 is arachidonic acid. When arachidonic acid in cellmembranes is replaced by omega 3, different, much less inflammatory prostaglandins, are released and that is an additional reason why the UV induced sunburn redness was reduced. In those studies, we found by chance that omega 3 supplementation could give excellent protection against a common sun-induced rash called polymorphic light eruption (PMLE) a sun-rash that affects up to 10% of women at the beginning of summer and which makes the summer an awful time for some.
KH: How frequent and serious is salicylate intolerance? What is the normal treatment and treatment duration?
PSF: The condition of salicylate intolerance mimics allergic conditions which may take the form of asthma, urticaria (nettle rash or hives) and even full blown anaphylactic shock which can be fatal. The symptoms can be very severe, requiring oral steroid therapy. It is estimated that up to 10% of severe asthmatics and 20-30% of those with severe urticaria have a significant degree of salicylate intolerance. Once this condition develops it is long lasting and even life-long. Strict avoidance of aspirin and non-steroidal anti-inflammatory drugs as well as avoidance of dietary sources of salicylates (dried fruits, peppermint and many others) is a key part of therapy but steroids as inhalers or oral tablets are usually required in often repeated courses.
KH: What is the biochemistry of this condition that might be helped with fish oil supplementation?
PSF: The known biochemistry of salicylate intolerance indicates that there are disturbances in the patterns of inflammatory mediators such that excessive quantities of so-called 4 series leukotrienes are released. Arachidonic acid released by various triggers including UV light and
allergic reactions, can be processed down at least 2 main pathways. One of these, processed largely by the enzyme cyclo-oxygenase, generates
prostaglandins. The other, processed mainly by the lipoxygenase enzymes,
converts the arachdonic acid into the highly inflammatory 4 series leukotrienes. These cause tightening of the muscle in the walls of the airways, producing spasm (asthma) and can caus changes to the small blood vessels in the skin that result in urticaria. One of the main actions of aspirin or non-steroidal anti-inflammatories is to block the cyclo-oxygenase enzyme preventing conversion of arachidonic acid into the pro-inflammatory prostaglandins. However, in salicylate intolerant individuals, this can have the effect of diverting the arachidonic acid down the other pathway to be converted to the asthma inducing 4 series leukotrienes. From my knowledge of the effects of omega 3s in replacing arachidonic acid as the precursor, resulting in formation of much less inflammatory prostaglandins and leukotrienes, I thought it would be of interest to ask some people suffering from severe salicylate intolerance to try the effects of dietary supplementation with omega 3-rich fish oils.
KH: Where did you come up with a dose of 10 gms of fish oil per day? Was it given in a single dose of divided dose? With meals or away from meals?
PSF: In our previous studies of the effects of omega 3s in UV-induced skin damage, we had given 10 grams of fish oil daily because there was no previous knowledge of what the right level might be and we did not want to risk missing an effect by giving too little. The 10 capsules
are taken in 3 doses with meals. We have asked people to take the 10 grams until there is a clear effect and then to try reducing the dose to see what is the lowest dose that still produces benefit. Most people cannot reduce below 8 grams.
KH: How much eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)was in each capsule and how many capsules were taken daily?
PSF: Each 1 gram capsule contains 180mg of EPA and 120mg of DHA.
KH: Were fatty acid levels done before, during or after the study? If so did they correlate with symptoms and improvement?
PSF: So far this has been a pilot study without any fundamental scientific measurements that might confirm the theoretical ideas about what is going on. We are trying to gain grant support in order to perform a rigorous and full study that will involve giving placebo oils and analyzing both the clinical effects and measuring the various fatty acids and mediators.
KH: Can you tell us about your study and the basic results?
PSF: This was an open pilot study. Once we conceived the idea, we explained the theory of why it might give benefit and invited interested and willing patients to obtain the omega 3-rich oils and to take them as a dietary supplement. The first patient was the most severe referred by our
asthma physicians because she also had very resistant urticarial nettle rash. She was taking long-term oral steroids for the control of her asthma. After one month of omega 3 supplementation her symptoms reduced greatly and she was able to discontinue the steroids. After 2 months she was symptom free and off all treatment.This was such a dramatic response that we wanted to repeat it. Therefore, from our clinics, we identified 3 other patients with similar severe symptoms. The same benefit was seen in 2 but the third could not tolerate the fish oil, finding it gave her bloating and discomfort. We also asked 2 patients with severe urticaria but with no evidence of salicylate intolerance to try the fish oils but they obtained no benefit. We felt this was such a clear and striking effect that we should report it in the medical literature as a prelude to going to a full and rigorous double-blind controlled study.
KH: Were there any side effects with the fish oil therapy? How was the patient compliance?
PSF: There are some side effects of high dose fish oil therapy including flatulence, abdominal discomfort, occasionally weight gain and rarely, disturbances of blood clotting that can lead to bleeding gums and very rarely to more significant bleeding. As long as the oils are taken in
divided doses with meals the symptoms and side-effects are minimal. However, up to 10% of people do find it is too oily or even too fishy to tolerate.
KH: Who is a candidate for fish oil therapy? All salicylate intolerant patients? How would you choose who should receive this therapy?
PSF: We have not yet defined who would be the best candidates for fish oil supplementation hopefully that should emerge from the bigger study we wish to undertake.
KH: Could you help the fish oil therapy in these salicylate intolerant subjects by reducing or eliminating preformed arachidonic acid in the diet by eliminating meat, especially red meat, eggs and dairy fat, while increasing vegetables, especially green leafy vegetables, certain nuts
such as walnuts, and cold water fish? Would you not expect a better response from the fish oil if these dietary guidelines were attempted? Or they might need less fish oil to gain protection from salicylate intolerance?
PSF: The important dietary approach is to exclude aspirin related drugs and salicylate containing foods. Many foods contain significant amounts of salicylates- dried fruits such as raisins and sultanas have the highest levels (so muesli and fruit cakes are out), most vegetables contain
significant quantities of salicylates and peppermint, as in chewing gum and toothpaste, is often a trigger. It is virtually impossible to cut out the dietary precursors of arachidonic acid, which are the omega 6 containing oils mostly used in cooking.
KH: Do you have any further comments on this very interesting subject?
PSF: We think this is a very exciting discovery it is not every day that a cure for a difficult and even dangerous condition is discovered, and the safety and simplicity of the treatment makes a very attractive alternative to the various drugs and their side effects. However, these findings are preliminary, from a very small open study and they must be confirmed in larger numbers of people in properly designed placebo-controlled
double blind studies.
Kirk Hamilton: Can you please share with us your educational background
and current position?
Peter S. Friedmann: I trained in Medicine at Cambridge University and University College Hospital London. I did further training in immunology and dermatology. I was Professor of Dermatology at Liverpool University from 1990 -1997 and Professor of Dermatology in the University of
Southampton from 1998 until 2007.
KH: What got you interested in studying the role of fish oilsupplementation and salicylate intolerance?
PSF: Twelve years ago I first got involved in studying whether fish oils rich in omega 3 fatty acids were able to protect against tissue damage caused by free radicals. The source of free radicals we were interested in was ultraviolet light. We showed that dietary supplementation with omega 3 conferred significant protection against many of the damaging effects of UV light, the most obvious of which was the sunburn effect. The main chemicals that are responsible for the redness of sunburn are prostaglandins , particularly prostaglandin E2 (PGE2). We showed that the omega 3 soaked up the free radicals and there was much less release of PGE2 with much less sunburn. It is now also well known that the cell membrane fat (lipid) that is released as a precursor of PGE2 is arachidonic acid. When arachidonic acid in cellmembranes is replaced by omega 3, different, much less inflammatory prostaglandins, are released and that is an additional reason why the UV induced sunburn redness was reduced. In those studies, we found by chance that omega 3 supplementation could give excellent protection against a common sun-induced rash called polymorphic light eruption (PMLE) a sun-rash that affects up to 10% of women at the beginning of summer and which makes the summer an awful time for some.
KH: How frequent and serious is salicylate intolerance? What is the normal treatment and treatment duration?
PSF: The condition of salicylate intolerance mimics allergic conditions which may take the form of asthma, urticaria (nettle rash or hives) and even full blown anaphylactic shock which can be fatal. The symptoms can be very severe, requiring oral steroid therapy. It is estimated that up to 10% of severe asthmatics and 20-30% of those with severe urticaria have a significant degree of salicylate intolerance. Once this condition develops it is long lasting and even life-long. Strict avoidance of aspirin and non-steroidal anti-inflammatory drugs as well as avoidance of dietary sources of salicylates (dried fruits, peppermint and many others) is a key part of therapy but steroids as inhalers or oral tablets are usually required in often repeated courses.
KH: What is the biochemistry of this condition that might be helped with fish oil supplementation?
PSF: The known biochemistry of salicylate intolerance indicates that there are disturbances in the patterns of inflammatory mediators such that excessive quantities of so-called 4 series leukotrienes are released. Arachidonic acid released by various triggers including UV light and
allergic reactions, can be processed down at least 2 main pathways. One of these, processed largely by the enzyme cyclo-oxygenase, generates
prostaglandins. The other, processed mainly by the lipoxygenase enzymes,
converts the arachdonic acid into the highly inflammatory 4 series leukotrienes. These cause tightening of the muscle in the walls of the airways, producing spasm (asthma) and can caus changes to the small blood vessels in the skin that result in urticaria. One of the main actions of aspirin or non-steroidal anti-inflammatories is to block the cyclo-oxygenase enzyme preventing conversion of arachidonic acid into the pro-inflammatory prostaglandins. However, in salicylate intolerant individuals, this can have the effect of diverting the arachidonic acid down the other pathway to be converted to the asthma inducing 4 series leukotrienes. From my knowledge of the effects of omega 3s in replacing arachidonic acid as the precursor, resulting in formation of much less inflammatory prostaglandins and leukotrienes, I thought it would be of interest to ask some people suffering from severe salicylate intolerance to try the effects of dietary supplementation with omega 3-rich fish oils.
KH: Where did you come up with a dose of 10 gms of fish oil per day? Was it given in a single dose of divided dose? With meals or away from meals?
PSF: In our previous studies of the effects of omega 3s in UV-induced skin damage, we had given 10 grams of fish oil daily because there was no previous knowledge of what the right level might be and we did not want to risk missing an effect by giving too little. The 10 capsules
are taken in 3 doses with meals. We have asked people to take the 10 grams until there is a clear effect and then to try reducing the dose to see what is the lowest dose that still produces benefit. Most people cannot reduce below 8 grams.
KH: How much eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)was in each capsule and how many capsules were taken daily?
PSF: Each 1 gram capsule contains 180mg of EPA and 120mg of DHA.
KH: Were fatty acid levels done before, during or after the study? If so did they correlate with symptoms and improvement?
PSF: So far this has been a pilot study without any fundamental scientific measurements that might confirm the theoretical ideas about what is going on. We are trying to gain grant support in order to perform a rigorous and full study that will involve giving placebo oils and analyzing both the clinical effects and measuring the various fatty acids and mediators.
KH: Can you tell us about your study and the basic results?
PSF: This was an open pilot study. Once we conceived the idea, we explained the theory of why it might give benefit and invited interested and willing patients to obtain the omega 3-rich oils and to take them as a dietary supplement. The first patient was the most severe referred by our
asthma physicians because she also had very resistant urticarial nettle rash. She was taking long-term oral steroids for the control of her asthma. After one month of omega 3 supplementation her symptoms reduced greatly and she was able to discontinue the steroids. After 2 months she was symptom free and off all treatment.This was such a dramatic response that we wanted to repeat it. Therefore, from our clinics, we identified 3 other patients with similar severe symptoms. The same benefit was seen in 2 but the third could not tolerate the fish oil, finding it gave her bloating and discomfort. We also asked 2 patients with severe urticaria but with no evidence of salicylate intolerance to try the fish oils but they obtained no benefit. We felt this was such a clear and striking effect that we should report it in the medical literature as a prelude to going to a full and rigorous double-blind controlled study.
KH: Were there any side effects with the fish oil therapy? How was the patient compliance?
PSF: There are some side effects of high dose fish oil therapy including flatulence, abdominal discomfort, occasionally weight gain and rarely, disturbances of blood clotting that can lead to bleeding gums and very rarely to more significant bleeding. As long as the oils are taken in
divided doses with meals the symptoms and side-effects are minimal. However, up to 10% of people do find it is too oily or even too fishy to tolerate.
KH: Who is a candidate for fish oil therapy? All salicylate intolerant patients? How would you choose who should receive this therapy?
PSF: We have not yet defined who would be the best candidates for fish oil supplementation hopefully that should emerge from the bigger study we wish to undertake.
KH: Could you help the fish oil therapy in these salicylate intolerant subjects by reducing or eliminating preformed arachidonic acid in the diet by eliminating meat, especially red meat, eggs and dairy fat, while increasing vegetables, especially green leafy vegetables, certain nuts
such as walnuts, and cold water fish? Would you not expect a better response from the fish oil if these dietary guidelines were attempted? Or they might need less fish oil to gain protection from salicylate intolerance?
PSF: The important dietary approach is to exclude aspirin related drugs and salicylate containing foods. Many foods contain significant amounts of salicylates- dried fruits such as raisins and sultanas have the highest levels (so muesli and fruit cakes are out), most vegetables contain
significant quantities of salicylates and peppermint, as in chewing gum and toothpaste, is often a trigger. It is virtually impossible to cut out the dietary precursors of arachidonic acid, which are the omega 6 containing oils mostly used in cooking.
KH: Do you have any further comments on this very interesting subject?
PSF: We think this is a very exciting discovery it is not every day that a cure for a difficult and even dangerous condition is discovered, and the safety and simplicity of the treatment makes a very attractive alternative to the various drugs and their side effects. However, these findings are preliminary, from a very small open study and they must be confirmed in larger numbers of people in properly designed placebo-controlled
double blind studies.
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