Guest guest Posted December 29, 2004 Report Share Posted December 29, 2004 Hi Alan, Where did you copy that cite from? Nutr Res Rev? It makes sense to me IF I think n-3 PUFA is fish oil. Not ALA. Regards ----- Original Message ----- From: old542000 Sent: Monday, December 27, 2004 3:05 PM Subject: [ ] n-3 PUFAs in cancer Nutr Res Rev (2004),17 ,177–192 n -3 Polyunsaturated fatty acids throughout the cancer trajectory:in & #64258;uence on disease incidence,progression,response to therapy andcancer-associated cachexia Evidence from epidemiological studies suggests that diets rich in n -3 PUFA may be associatedwith reduced cancer risk.These observations have formed the rationale for exploring the mecha-nisms by which n -3 PUFA may be chemoprotective and have resulted in signi & #64257;cant advances inour mechanistic understanding of n -3 PUFA action on tumour growth.Various interrelated andintegrated mechanisms may be at work by which n -3 PUFA in & #64258;uence cancer at all stages of ini-tiation,promotion,progression,and neoplastic transformation.More recently,experimentalstudies have reported enhanced tumour cell death with chemotherapy when & #64257;sh oil is providedwhile toxic side effects to the host are reduced.Furthermore,cancer-associated wasting has beenshown to be attenuated by & #64257;sh oil supplementation.Clinical evidence suggests that the n -3PUFA status of newly diagnosed cancer patients and individuals undergoing chemotherapy islow.Therefore,both the disease itself and therapeutic treatments may be contributing factors inthe decline of n -3 PUFA status.Dietary supplementation to maintain and replenish n -3 PUFAstatus at key points in the cancer disease trajectory may provide additional health bene & #64257;ts andan enhanced quality of life.The present review will focus on and critically examine currentresearch efforts related to the putative anti-cancer effects of n -3 PUFA and their suggested abil-ity to palliate cancer-associated and treatment-associated symptoms. ... Dietary polyunsaturated fatty acids:prevention andrisk reduction of cancerThere are several prevailing streams of thought regardingthe contribution of dietary fat to cancer.Animal studies inparticular have allowed the delineation of these pointsthrough the use of diets with de & #64257;ned fat components.Thequantity and energy contribution of fat to energy intake andthe composition of that fat independently in & #64258;uence cancerrisk and the growth of established tumours.Within fat com-position,the importance of the PUFA:saturated fatty acidsratio in the diet as well as the levels of different speci & #64257;cfatty acids on tumour incidence,growth and anti-tumourimmune responses have been recognised (Sasaki et al.1998; et al.2001).The balance between n -3 andn -6 PUFA is important,but this may also extend to otherbiologically active fatty acids such as conjugated linoleicacid (Wahle & Heys,2002),oleic acid (Bartsch et al.1999),and individual fatty acids within the n -3 and n -6PUFA family. Epidemiological and experimental evidenceThe results from epidemiological studies examining theeffect of & #64257;sh consumption on the development of humancancer has been reviewed extensively (de Deckere,1999;Cohen,2000;Weisburger,2000;Zock,2001;Temple,2002;Dennis et al.2003;Terry et al.2003).Although stud-ies suggest a bene & #64257;cial and protective effect of & #64257;sh oil con-sumption,overall,epidemiological evidence cannot be usedto de & #64257;nitively conclude that n -3 PUFA consumption ischemoprotective.There are two signi & #64257;cant shortcomingsinherent in most epidemiological studies.Reviewed collec-tively,studies fail to demonstrate that cancer risk or tumourburden is lowered by n -3 PUFA consumption.Second,suchapproaches do not rigorously address mechanisms ofaction.The inconsistent & #64257;ndings re & #64258;ect the dif & #64257;culty inevaluating the relative contribution of minor fatty acids inthe diet which are not easily dissected from a large matrixof confounders.The list of confounders appears endless andhighlights the many challenges in interpreting these typesof studies.Given the recognised limitations of various epidemiologi-cal study formats (i.e.case –control,retrospective andprospective studies;Temple,2002;Dennis et al.2003),thefact remains that there is a trend that suggests a role fordietary n -3 PUFA in cancer prevention.Whereas the epi-demiological data have primarily provided correlative evi-dence for cancer prevention and risk reduction,experimentaldata from animal models and cell lines demonstrate thatdietary n -3 PUFA can inhibit tumour growth in a variety ofcancer models such as breast,colon and prostate (e etal.1999;Connolly et al.1999;Chen & Istfan,2000;Chunget al.2001).A large body of in vitro and animal model datalinks n -3 PUFA to physiological and morphological changesthat reduce tumour weight,size and multiplicity.Various mechanisms may be at work by which n -3PUFA can prevent cancer at all stages of initiation,promo-tion,progression,and then neoplastic transformation ofbenign tumours to malignant tumours.A survey of the liter-ature reveals a multitude of mechanisms currently beinginvestigated,broadly related to apoptosis,cell proliferation,cell signalling,gene regulation,angiogenesis and metasta-sis;these are summarised in Fig.1.Well-studied mecha-nisms have been discussed in detail in several recentreviews (Jiang et al.1998;Bartsch et al.1999;Bougnoux,1999;Rose & Connolly,1999 b ,2000;Simopoulos,1999,2002;Woutersen et al.1999;Stoll,2001;Hardman,2002;McEntee & Whelan,2002;Chajes & Bougnoux,2003);therefore,we will highlight,or summarise in brief,areas ofemerging interest. ... most epidemiological studies.Reviewed collec-tively,studies fail to demonstrate that cancer risk or tumourburden is lowered by n -3 PUFA consumption.Second,suchapproaches do not rigorously address mechanisms ofaction.The inconsistent & #64257;ndings re & #64258;ect the dif & #64257;culty inevaluating the relative contribution of minor fatty acids inthe diet which are not easily dissected from a large matrixof confounders.The list of confounders appears endless andhighlights the many challenges in interpreting these typesof studies.Given the recognised limitations of various epidemiologi-cal study formats (i.e.case –control,retrospective andprospective studies;Temple,2002;Dennis et al.2003),thefact remains that there is a trend that suggests a role fordietary n -3 PUFA in cancer prevention.Whereas the epi-demiological data have primarily provided correlative evi-dence for cancer prevention and risk reduction,experimentaldata from animal models and cell lines demonstrate thatdietary n -3 PUFA can inhibit tumour growth in a variety ofcancer models such as breast,colon and prostate (e etal.1999;Connolly et al.1999;Chen & Istfan,2000;Chunget al.2001).A large body of in vitro and animal model datalinks n -3 PUFA to physiological and morphological changesthat reduce tumour weight,size and multiplicity.Various mechanisms may be at work by which n -3PUFA can prevent cancer at all stages of initiation,promo-tion,progression,and then neoplastic transformation ofbenign tumours to malignant tumours.A survey of the liter-ature reveals a multitude of mechanisms currently beinginvestigated,broadly related to apoptosis,cell proliferation,cell signalling,gene regulation,angiogenesis and metasta-sis;these are summarised in Fig.1.Well-studied mecha-nisms have been discussed in detail in several recentreviews (Jiang et al.1998;Bartsch et al.1999;Bougnoux,1999;Rose & Connolly,1999 b ,2000;Simopoulos,1999,2002;Woutersen et al.1999;Stoll,2001;Hardman,2002;McEntee & Whelan,2002;Chajes & Bougnoux,2003);therefore,we will highlight,or summarise in brief,areas ofemerging interest. ... At diagnosisPopulation studies illustrate the large variation of n -3 levelsin blood and cell lipids in individuals from different coun-tries and regions (de Deckere,1999;Amiano et al.2002;Augustsson et al.2003;Terry et al.2003).Thus it seemsclear that any reports of PUFA status in cancer patients atany stage must be interpreted in the light of national orregional context.In a comprehensive review of intakes of & #64257;sh and marine fatty acids in relation to hormone-relatedcancers,Terry et al.(2003)point out that the differencebetween the highest and lowest n -3 intakes internationallyare as much as 15-fold (i.e.1500,400 and 100 mg/d inJapan,Scandinavian countries and North America,respec-tively).The dietary n -6:n -3 fatty acids ratio shows a similardegree of variation.The fatty acid status of patients at the time of a cancerdiagnosis can be assumed to be a function of previousdietary intakes and the effect,if any,speci & #64257;c to disease anddisease stage.Only one study to date has reported plasmafatty acid levels in patients with a new diagnosis of pancre-atic,non-small-cell lung and stomach or oesophageal cancer(Zuijdgeest-van Leeuwen et al.2002).The disease stage wasnot reported;however,up to 23 %of patients had metastaticcancer at diagnosis.These were compared with normalhealthy controls from a local population (The Netherlands).This report suggests impairments in essential fatty acidmetabolism as the levels of fatty acids of the n -6 and n -3series typically were lower than those of healthy subjects;however,the degree of difference and the speci & #64257;c fatty acidsthat are affected appear to vary between cancer types. ... The information on fatty acid status and fatty acid sup-plementation in patients with advanced cancer,takentogether,provides a rationale for developing dietary recom-mendations based on formal assessments of fatty acid statusand fatty acid requirements.This is particularly pertinent incountries where n -3 fatty acid intakes are generally low andn -6:n -3 ratios are high.Current intakes of total n -3 fattyacids are about 1 ·6 g/d (0 ·7 %of energy intake)in the USA(Kris-Etherton et al.2002).Of this,á -linolenic acidaccounts for about 1 ·4 g/d,and only 0 ·1 to 0 ·2 g/d comesfrom EPA and DHA.Formal population-based dietary rec-ommendations for n -3 fatty acids have been made by theWHO and the North Atlantic Treaty Organization and alsoexist in several countries including Canada,Sweden,theUK,Australia and Japan.Typical recommendations forEPA+DHA are 0 ·3 to 0 ·5 g/d,and for á -linolenic acid are0 ·8 to 1 ·1 g/d.Dietary reference intakes for energy andmacronutrients were recently released by the Food andNutrition Board,Institute of Medicine,and The NationalAcademies (USA),in collaboration with Health Canada. These institutions placed the acceptable macronutrient dis-tribution range for á -linolenic acid at 0 ·6 to 1 ·2 %ofenergy,or 1 ·3 to 2 ·7 g/d on the basis of a 8370 kJ (2000kcal)diet (Kris-Etherton et al.2002).This is nearly tentimes the current intake of EPA+DHA of typical NorthAmericans.???????????????? In view of suggestions that the n -3 PUFA statusin cancer patients may be even poorer than in the generalpopulation,it would appear obvious that dietary supple-mentation to maintain and replenish n -3 PUFA status at keypoints in the cancer disease trajectory is required.Dietaryrecommendations for such supplementation have not beenadopted by cancer centres or agencies,and the number andtype of supplements and n -3-containing products suited tothe patient populations are very limited.For those wishingto advise upon or implement n -3 supplementation,theAmerican Heart Association position paper on & #64257;sh oil andn -3 fatty acid consumption (Kris-Etherton et al.2002)is auseful reference.Cheers, Alan Pater Quote Link to comment Share on other sites More sharing options...
Guest guest Posted December 29, 2004 Report Share Posted December 29, 2004 Hi JW: Yes. And now, taking a little further my speculation that likely the link between ALA and prostate cancer may be aflatoxin, I wonder whether that may possibly also explain why there are indications starch is not completely benign - even if you do not count its calories. This makes fish seem like an even greater benefit, since it will not be a source of aflatoxin, unless/until they start feeding grain to fish. And also why fish is superior to meat of any kind when the animals are fed grains. (Since the aflatoxin does turn up in meat when the animals are fed aflatoxin-tainted grain). Certainly the above links are not yet all proven. But it certainly seems to fit well with the facts we know. But it is best to eat the smaller fish, since they will not have had time to accumulate mercury, etc.. Rodney. --- In , " jwwright " <jwwright@e...> wrote: > Hi Alan, > Where did you copy that cite from? Nutr Res Rev? > > It makes sense to me IF I think n-3 PUFA is fish oil. Not ALA. > > Regards > ----- Original Message ----- > From: old542000 > > Sent: Monday, December 27, 2004 3:05 PM > Subject: [ ] n-3 PUFAs in cancer > > > Nutr Res Rev (2004),17 ,177-192 > n -3 Polyunsaturated fatty acids throughout the cancer trajectory: > in & #64258;uence on disease incidence,progression,response to therapy and > cancer-associated cachexia > > Evidence from epidemiological studies suggests that diets rich in > n -3 PUFA may be associated > with reduced cancer risk.These observations have formed the rationale > for exploring the mecha- > nisms by which n -3 PUFA may be chemoprotective and have resulted in > signi & #64257;cant advances in > our mechanistic understanding of n -3 PUFA action on tumour > growth.Various interrelated and > integrated mechanisms may be at work by which n -3 PUFA in & #64258;uence > cancer at all stages of ini- > tiation,promotion,progression,and neoplastic transformation.More > recently,experimental > studies have reported enhanced tumour cell death with chemotherapy > when & #64257;sh oil is provided > while toxic side effects to the host are reduced.Furthermore,cancer- > associated wasting has been > shown to be attenuated by & #64257;sh oil supplementation.Clinical evidence > suggests that the n -3 > PUFA status of newly diagnosed cancer patients and individuals > undergoing chemotherapy is > low.Therefore,both the disease itself and therapeutic treatments may > be contributing factors in > the decline of n -3 PUFA status.Dietary supplementation to maintain > and replenish n -3 PUFA > status at key points in the cancer disease trajectory may provide > additional health bene & #64257;ts and > an enhanced quality of life.The present review will focus on and > critically examine current > research efforts related to the putative anti-cancer effects of n -3 > PUFA and their suggested abil- > ity to palliate cancer-associated and treatment-associated symptoms. > > ... Dietary polyunsaturated fatty acids:prevention and > risk reduction of cancer > There are several prevailing streams of thought regarding > the contribution of dietary fat to cancer.Animal studies in > particular have allowed the delineation of these points > through the use of diets with de & #64257;ned fat components.The > quantity and energy contribution of fat to energy intake and > the composition of that fat independently in & #64258;uence cancer > risk and the growth of established tumours.Within fat com- > position,the importance of the PUFA:saturated fatty acids > ratio in the diet as well as the levels of different speci & #64257;c > fatty acids on tumour incidence,growth and anti-tumour > immune responses have been recognised (Sasaki et al. > 1998; et al.2001).The balance between n -3 and > n -6 PUFA is important,but this may also extend to other > biologically active fatty acids such as conjugated linoleic > acid (Wahle & Heys,2002),oleic acid (Bartsch et al. > 1999),and individual fatty acids within the n -3 and n -6 > PUFA family. > Epidemiological and experimental evidence > The results from epidemiological studies examining the > effect of & #64257;sh consumption on the development of human > cancer has been reviewed extensively (de Deckere,1999; > Cohen,2000;Weisburger,2000;Zock,2001;Temple, > 2002;Dennis et al.2003;Terry et al.2003).Although stud- > ies suggest a bene & #64257;cial and protective effect of & #64257;sh oil con- > sumption,overall,epidemiological evidence cannot be used > to de & #64257;nitively conclude that n -3 PUFA consumption is > chemoprotective.There are two signi & #64257;cant shortcomings > inherent in most epidemiological studies.Reviewed collec- > tively,studies fail to demonstrate that cancer risk or tumour > burden is lowered by n -3 PUFA consumption.Second,such > approaches do not rigorously address mechanisms of > action.The inconsistent & #64257;ndings re & #64258;ect the dif & #64257;culty in > evaluating the relative contribution of minor fatty acids in > the diet which are not easily dissected from a large matrix > of confounders.The list of confounders appears endless and > highlights the many challenges in interpreting these types > of studies. > Given the recognised limitations of various epidemiologi- > cal study formats (i.e.case -control,retrospective and > prospective studies;Temple,2002;Dennis et al.2003),the > fact remains that there is a trend that suggests a role for > dietary n -3 PUFA in cancer prevention.Whereas the epi- > demiological data have primarily provided correlative evi- > dence for cancer prevention and risk reduction,experimental > data from animal models and cell lines demonstrate that > dietary n -3 PUFA can inhibit tumour growth in a variety of > cancer models such as breast,colon and prostate (e et > al.1999;Connolly et al.1999;Chen & Istfan,2000;Chung > et al.2001).A large body of in vitro and animal model data > links n -3 PUFA to physiological and morphological changes > that reduce tumour weight,size and multiplicity. > Various mechanisms may be at work by which n -3 > PUFA can prevent cancer at all stages of initiation,promo- > tion,progression,and then neoplastic transformation of > benign tumours to malignant tumours.A survey of the liter- > ature reveals a multitude of mechanisms currently being > investigated,broadly related to apoptosis,cell proliferation, > cell signalling,gene regulation,angiogenesis and metasta- > sis;these are summarised in Fig.1.Well-studied mecha- > nisms have been discussed in detail in several recent > reviews (Jiang et al.1998;Bartsch et al.1999;Bougnoux, > 1999;Rose & Connolly,1999 b ,2000;Simopoulos,1999, > 2002;Woutersen et al.1999;Stoll,2001;Hardman,2002; > McEntee & Whelan,2002;Chajes & Bougnoux,2003); > therefore,we will highlight,or summarise in brief,areas of > emerging interest. > > ... most epidemiological studies.Reviewed collec- > tively,studies fail to demonstrate that cancer risk or tumour > burden is lowered by n -3 PUFA consumption.Second,such > approaches do not rigorously address mechanisms of > action.The inconsistent & #64257;ndings re & #64258;ect the dif & #64257;culty in > evaluating the relative contribution of minor fatty acids in > the diet which are not easily dissected from a large matrix > of confounders.The list of confounders appears endless and > highlights the many challenges in interpreting these types > of studies. > Given the recognised limitations of various epidemiologi- > cal study formats (i.e.case -control,retrospective and > prospective studies;Temple,2002;Dennis et al.2003),the > fact remains that there is a trend that suggests a role for > dietary n -3 PUFA in cancer prevention.Whereas the epi- > demiological data have primarily provided correlative evi- > dence for cancer prevention and risk reduction,experimental > data from animal models and cell lines demonstrate that > dietary n -3 PUFA can inhibit tumour growth in a variety of > cancer models such as breast,colon and prostate (e et > al.1999;Connolly et al.1999;Chen & Istfan,2000;Chung > et al.2001).A large body of in vitro and animal model data > links n -3 PUFA to physiological and morphological changes > that reduce tumour weight,size and multiplicity. > Various mechanisms may be at work by which n -3 > PUFA can prevent cancer at all stages of initiation,promo- > tion,progression,and then neoplastic transformation of > benign tumours to malignant tumours.A survey of the liter- > ature reveals a multitude of mechanisms currently being > investigated,broadly related to apoptosis,cell proliferation, > cell signalling,gene regulation,angiogenesis and metasta- > sis;these are summarised in Fig.1.Well-studied mecha- > nisms have been discussed in detail in several recent > reviews (Jiang et al.1998;Bartsch et al.1999;Bougnoux, > 1999;Rose & Connolly,1999 b ,2000;Simopoulos,1999, > 2002;Woutersen et al.1999;Stoll,2001;Hardman,2002; > McEntee & Whelan,2002;Chajes & Bougnoux,2003); > therefore,we will highlight,or summarise in brief,areas of > emerging interest. > > ... At diagnosis > Population studies illustrate the large variation of n -3 levels > in blood and cell lipids in individuals from different coun- > tries and regions (de Deckere,1999;Amiano et al.2002; > Augustsson et al.2003;Terry et al.2003).Thus it seems > clear that any reports of PUFA status in cancer patients at > any stage must be interpreted in the light of national or > regional context.In a comprehensive review of intakes of > & #64257;sh and marine fatty acids in relation to hormone-related > cancers,Terry et al.(2003)point out that the difference > between the highest and lowest n -3 intakes internationally > are as much as 15-fold (i.e.1500,400 and 100 mg/d in > Japan,Scandinavian countries and North America,respec- > tively).The dietary n -6:n -3 fatty acids ratio shows a similar > degree of variation. > The fatty acid status of patients at the time of a cancer > diagnosis can be assumed to be a function of previous > dietary intakes and the effect,if any,speci & #64257;c to disease and > disease stage.Only one study to date has reported plasma > fatty acid levels in patients with a new diagnosis of pancre- > atic,non-small-cell lung and stomach or oesophageal cancer > (Zuijdgeest-van Leeuwen et al.2002).The disease stage was > not reported;however,up to 23 %of patients had metastatic > cancer at diagnosis.These were compared with normal > healthy controls from a local population (The Netherlands). > This report suggests impairments in essential fatty acid > metabolism as the levels of fatty acids of the n -6 and n -3 > series typically were lower than those of healthy subjects; > however,the degree of difference and the speci & #64257;c fatty acids > that are affected appear to vary between cancer types. > > ... The information on fatty acid status and fatty acid sup- > plementation in patients with advanced cancer,taken > together,provides a rationale for developing dietary recom- > mendations based on formal assessments of fatty acid status > and fatty acid requirements.This is particularly pertinent in > countries where n -3 fatty acid intakes are generally low and > n -6:n -3 ratios are high.Current intakes of total n -3 fatty > acids are about 1 ·6 g/d (0 ·7 %of energy intake)in the USA > (Kris-Etherton et al.2002).Of this,á -linolenic acid > accounts for about 1 ·4 g/d,and only 0 ·1 to 0 ·2 g/d comes > from EPA and DHA.Formal population-based dietary rec- > ommendations for n -3 fatty acids have been made by the > WHO and the North Atlantic Treaty Organization and also > exist in several countries including Canada,Sweden,the > UK,Australia and Japan.Typical recommendations for > EPA+DHA are 0 ·3 to 0 ·5 g/d,and for á -linolenic acid are > 0 ·8 to 1 ·1 g/d.Dietary reference intakes for energy and > macronutrients were recently released by the Food and > Nutrition Board,Institute of Medicine,and The National > Academies (USA),in collaboration with Health Canada. > > > These institutions placed the acceptable macronutrient dis- > tribution range for á -linolenic acid at 0 ·6 to 1 ·2 %of > energy,or 1 ·3 to 2 ·7 g/d on the basis of a 8370 kJ (2000 > kcal)diet (Kris-Etherton et al.2002).This is nearly ten > times the current intake of EPA+DHA of typical North > Americans.???????????????? > > > > In view of suggestions that the n -3 PUFA status > in cancer patients may be even poorer than in the general > population,it would appear obvious that dietary supple- > mentation to maintain and replenish n -3 PUFA status at key > points in the cancer disease trajectory is required.Dietary > recommendations for such supplementation have not been > adopted by cancer centres or agencies,and the number and > type of supplements and n -3-containing products suited to > the patient populations are very limited.For those wishing > to advise upon or implement n -3 supplementation,the > American Heart Association position paper on & #64257;sh oil and > n -3 fatty acid consumption (Kris-Etherton et al.2002)is a > useful reference. > > > Cheers, Alan Pater Quote Link to comment Share on other sites More sharing options...
Guest guest Posted December 29, 2004 Report Share Posted December 29, 2004 Hi All, Our Queen Elizabet II Library E-jornals. Also, the authors were Vickie E.Baracos ,Vera C.Mazurak and W.L.Ma. Cheers, Al. --- In , " jwwright " <jwwright@e...> wrote: > Hi Alan, > Where did you copy that cite from? Nutr Res Rev? > > It makes sense to me IF I think n-3 PUFA is fish oil. Not ALA. > > Regards > ----- Original Message ----- > From: old542000 > > Sent: Monday, December 27, 2004 3:05 PM > Subject: [ ] n-3 PUFAs in cancer > > > Nutr Res Rev (2004),17 ,177-192 > n -3 Polyunsaturated fatty acids throughout the cancer trajectory: > in & #64258;uence on disease incidence,progression,response to therapy and > cancer-associated cachexia > Quote Link to comment Share on other sites More sharing options...
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