Prostaglandins, Leukotrienes and Essential Fatty Acids 85 (2011) 405406

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Prostaglandins, Leukotrienes and Essential Fatty Acids

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Letter to the editor

The omega-6/omega-3 ratio is of importance! In the paper of Guesnet et al. [1] in the present issue, the interaction between omega-6 and omega-3 fatty acids are illustrated in a thought-provoking way. It adds to the increasing evidence of a relation between the changes of this ratio in human and animal diets and the global epidemics of increases of metabolic complications as obesity, diabetes and neurological diseases. A recent paper analyzing the plurality of the obesity epidemics, Klimentidis et al. [2] express their concern about that also primates, domestic and feral animals are developing obesity and furthermore that a similar trend is observed in laboratory animals. The interesting fact is that neither the fat content of the chow or the fat intake of the human population has increased over the latest decades [3], so other environmental causes are probably involved. In the humans special interest has been focused on less physical activity depending on the technical development worldwide, but this alone cannot explain the obesity epidemics, which also involve infants and the population in developing countries [2]. It is certainly less likely in laboratory animals, whose living conditions have been rather the same for many decades. What really has changed during the last half of the 20th century is the quality of the fat, with an increased use of vegetable oils to exchange the diary fat and reduce the intake of saturated fat. Most of these oils have a very high content of omega-6 fatty acids, although the variation is large, being more than 100-fold between sunower oil and rape seed oil. Simultaneously the intake of sh has decreased, thus resulting in a lower intake of long chain omega-3 fatty acids, all together resulting in a much higher ratio of omega-6/omega-3 in food and fodder globally [4,5]. This is clearly documented in breast milk [6]. The fatty acid pattern is not always declared in animal experiments. Usually fat pattern, even in high-fat diets, are not declared on more than percentage levels. The use of oil has mainly substituted beef tallow or lard. Even when lard is used the composition is not expected to be similar as 50 years ago, since the feeding pattern of the animals have changed and that is reected in the meat and fat as well [7]. Since 15 years ago we have studied the inuence on adult diseases by modulation of essential fatty acids perinatally in rodents (8 11), on the development of diseases in the adult offspring. The control diet, which has mainly been based on ordinary chow have doubled the omega-6/ omega-3 ratio during this time in the standard chow. In the rst studies performed in 1998 the ratio of omega-6/omega-3 in the control diet was 6:1 [8], In 2002 it was 9:1 [9], in 2004 9:1 [10], and in 2006 12.5:1 [11] with the corresponding standard chow (2016 Teklad Global16% Protein Rodent Diet, Harlan Laboratories Inc., Madison, WI) to the latter with a ratio of 11:1. A standard high fat diet (D 12451, Research Diets Inc. New Brunswick, NJ) had a corresponding ratio of 17:1 [11]. Usually publications do not give fatty acid composition of either standard chow or high fat diet, but

with the same fat percentage a diet can have substantially different ratio as illustrated above. It would be reason to believe that the ratio might have been even lower than 6 many decades ago, when lard was used from animals eating grass [12]. There is a large controversy in the literature about if the ratio is of any importance. This is a little surprising when it is wellknown that the transformations of the omega-6 and omega3 fatty acids compete of the same desaturases and elongases. Some authors claim that it is the absolute amount, which is of any importance, and those also recommend very high intake of omega-6 as benecial [13]. However, the results in the studies these authors refer to in providing this advice, have been questioned [14]. By critically reviewing all basic information of the dietary intake in these studies the results seem to turn out quite different and not supporting the recommendation of up to 10 energy percent as omega-6 fatty acids as benecial [15] without also at the same time increase the omega-3 intake markedly. In studies where no harm is reported for high supply of omega-6 the basic omega-3 intake was high [16,17]. The high use of vegetable oils are spread worldwide by an increase of cultures of soy bean and corn on behalf of more traditional culturing. One third of the world production of corn goes to human feeding and two thirds to animal feeding. That results in a more than 5-fold increase of the ratio of omega-6 to omega-3 in animal products compared to traditional grass and ensilage feeding or compared to game meat [4,5]. The extended use of fast food also increases the intake of omega-6, since oil is often added in the preparation of such food and can increase the ratio omega-6/omega3 many hundred times compared to fresh food, like sh [1820]. A high omega-6 intake favours transformation of inammatory products, synthesized from arachidonic acid, the probably most important omega-6 fatty acid, important for our defense to infections and also for many other metabolic processes in the body. Too high intake, however, may contribute to the inammatory status characterizing many of the lifestyle diseases. Arachidonic acid also stimulates adipocyte transformation [21] and higher percentage of AA has been found in adipose tissue biopsies from obese children compared to normal weight children of the same age [22]. Others have reported high plasma concentrations of omega-6 fatty acids in obese children [23] and lower DHA in plasma phospholipids compared to age matched controls [24,25]. In a randomized cross-over double blind placebo study providing high physiological dose of omega-3 fatty acids for 3 months to obese adolescents, the omega-6/omega-3 ratio improved in plasma phospholipids, muscle and adipose tissue and the arterial distensibility and inammatory markers improved [26]. Also in healthy young adults a Mediterranean inspired diet for 4 weeks led to a signicant decrease in the omega-6/omega-3 ratio to about 2:1 and that was associated with an improvement in inammatory markers [27]. In healthy 4-yrsold in Sweden a low omega-3 intake was associated with higher

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Letter to the editor / Prostaglandins, Leukotrienes and Essential Fatty Acids 85 (2011) 405406

body weight, while a high fat intake, mainly consisting of saturated fat, was not [28]. In animal experiments when rodents have perinatally been given a diet with an omega-6/omega-3 ratio of 9:1, as is common in the diets of the Western countries, the animal developed as adults obesity and high insulin levels and male rats furthermore increased serum concentrations of triglycerides, and showed increased high blood pressure [10]. In male mice on a similar diet, the insulin curves after intraperitoneal glucose loading indicated insulin resistance in the adult animals, while intervention during lactation with a diet consistent of high amounts of saturated fat and no essential fatty acids (i.e. providing only small amounts from the dams stores), resulted in a lean phenotype of the offspring with resistance against obesity on a high fat diet and improved glucose tolerance [11]. In view of the high sensitivity also in the human males to develop metabolic syndrome and the now clear global epidemics also involving the domestic and laboratory animals, it is high time to seriously reconsider the general recommendations. Recently a study in children conrmed the results of the animal studies of an association between neonatally low DHA and high omega-6/omega-3 ratio, respectively, and risk of development of obesity [29]. According to earlier studies we probably do not need so much of the essential fatty acids [30]. The results from human and animal studies indicate the need for extended studies without preconceived ideas. Studies from the Dutch Famine during the Second World War indicate epigenetics to explain the long-term results [31]. Fatty acids are well-known to inuence gene expression related to lipid and glucose homeostasis [32]. The animal results referred to above have to be veried by epigenetic mechanisms, but obesity has already been indicated in 5 generations by omega-6 rich diet in rats [33]. All results in humans and animals challenge the present recommendations, and indicate that we have to decrease the omega-6 intake instead of extending the use of extra supply of omega-3 fatty acids. That would involve a paradigm shift, and would make it possible to preserve multiplicity of life and nature. Humanity would survive by arresting the plundering of the oceans. References
[1] P. Guesnet, S.-M. Lalalemand, J.-M. Alessandri, M. Jouin, S.-C. Cunnane, a-Linoleate reduces the dietary requirement for linoleate in the growing rat, Prostaglandins Leukotrines and Essential Fatty Acids 85 (2011) 353360. [2] Y.C. Klimentidis, T.M. Beasley, H.-Y. Lin, G. Murati, G.E. Glass, M. Guyton, et al., Canaries in the coal mine: a cross-species analysis of the plurality of obesity epidemics, Proceedings of the Royal Society B: Biological Science 278 (2011) 16261632. [3] D.M. Nguyen, H.B. El-Seraq, The epidemiology of obesity, Gastroenterology Clinics of North America 39 (2010) 17. [4] A.P. Simopoulos, Importance of the ratio of omega-6/omega-3 essential fatty acids:evolutionary aspects, World Review of Nutrition and Dietetics 92 (2003) 122. [5] T.L. Blasbalg, J.R. Hibbeln, C.E. Ramsden, S.F. Majchrzak, R.R. Rawlings, Changes in consumption of omega-3 and omega-6 fatty acids in the United Stated during the 20th century, American Journal of Clinical Nutrition 93 (2011) 950962. [6] G. Ailhaud, P. Guesnet, Fatty acid composition of fats is an early determinant of childhood obesity: a short review and an opinion, Obesity Review 5 (2004) 2126. [7] N.D. Scollan, N.-J. Choi, E. Kurt, A.V. Fisher, M. Enser, J.D. Wood, Manipulation the fatty acid composition of muscle and adipose tissue in beef cattle, British Journal of Nutrition 85 (2001) 115124. [8] M. Korotkova, B. Strandvik, Essential fatty acid deciency affects the fatty acid composition of the rat small intestinal and colonic mucosa differently, Biochimica et Biophysica Acta 1487 (2000) 319325. [9] M. Korotkova, B. Gabrielssson, M. Lonn, L.-A. Hanson, B. Strandvik, Leptin levels in rat offspring are modied by the ratio of linoleic to a-linolenic acid in the maternal diet, Journal of Lipid Research 43 (2002) 17431749. [10] M. Korotkova, B. Gabrielsson, A. Holm ang, B.M. Larsson, L.A. Hansson, B. Strandvik, Gender relatedlong-term effects in adult rats by perinatal dietary ratio on n-6/n-3 fatty acids, American Journal of PhysiologyRegulatory, Integrative and Comparative Physiology 288 (3) (2005) R575R579.

[11] V. Palsdottir, A. Wickman, N. Andersson, R. Hezaveh, B. Olsson, B.G. Gabrielsson, et al., Postnatal deciency of essential fatty acids in mice results in resistance to diet-induced obesity and low plasma insulin during adulthood, Prostaglandins Leukotrines and Essential Fatty Acids 84 (34) (2011) 8592 Epub 2010 Dec 21. [12] J.D. Wood, R.J. Richardson, G.R. Nute, A.V. Fischer, M.M. Campo, E. Kasapidou, P.R. Sheard, M. Enser, Effects of fatty acids on meat quality: a review, Meat Science 66 (2003) 2132. [13] W.S. Harris, D. Mozaffarian, E. Rimm, P. Kris-Etherton, L.L. Rudel, L.J. Appel, et al., Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention, Circulation 119 (2009) 902907. [14] C.E. Ramsden, J.R. Hibbeln, S.F. Majchrzak, J.M. Davis, n-6 fatty acid-specic and mixed polyunsaturate dietary interventions have different effect on CHD risk: a meta-analysis of randomised controlled trials, British Journal of Nutrition 104 (2010) 15861600. [15] P. Kris-Etherton, J. Fleming, W.S. Harris, The debate about n-6 polyunsaturated fatty acid recommendations for cardiovascular health, Journal of the American Dietetic Association 110 (2010) 201204. [16] L. Ferrucci, A. Cherubini, S. Bandinelli, B. Bartali, A. Corsi, F. Lauretani, A. Martin, C. Andres-Lacueva, U. Senin, J.M. Guralnik, Relationship of plasma polyunsaturated fatty acids to circulating inammatory markers, Journal of Clinical Endocrinology and Metabolism 91 (2006) 439446. [17] T. Pischon, S.E. Hankinson, G.S. Hotamisligil, N. Rifai, W.C. Willett, E.B. Rimm, Habitual dietary intake of n-3 and n-6 fatty acids in relation to inammatory markers among US men and women, Circulation 108 (2003) 155160. [18] S. Sampels, B. Strandvik, J. Pickova, Processed animal products with emphasis on polyunsaturated fatty acid content, European Journal of Lipid Science and Technology 111 (2009) 481488. [19] A. Maqbool, B. Strandvik, V.A. Stallings, The skinny on tuna fat: health implications, Public Health Nutrition 16 (2011) 16 [Epub ahead of print]. [20] Y. Wang, C. Lthane, K. AGhebremeskel, M.A. Crawford, Modern organic and broiler chickens sold for human consumption provide more energy from fat than protein, Public Health Nutrition 13 (2010) 400408. [21] G. Ailhaud, F. Massiera, P. Weill, P. Legrand, J.M. Alessandri, P. Guesnet, Temporal changes in dietary fats: role of n-6 polyunsaturated fatty acids in excessive adipose tissue development and relationship to obesity, Progress in Lipid Research 45 (2006) 203236. [22] S.C. Savva, C. Chadjigeorgiou, C. Hatzis, M. Kyriakakis, G. Tsimbinos, M. Tornaritis, et al., Association of adipose tissue arachidonic acid content with BMI and overweight status in children from Cyprus and Crete, British Journal of Nutrition 9 (2004) 643649. [23] T. Desci, D. Molnar, B. Koletzko, Long chain polyunsaturated fatty acids in plasma lipids of obese children, Lipids 31 (1996) 305311. [24] M. Karlsson, S. Marild, J. Brandberg, L. Lonn, P. Friberg, B. Strandvik, Serum phospholipid fatty acids, adipose tissue, and metabolic markers in obese adolescents, Obesity (Silver Spring) 14 (2006) 19311939. [25] E. Saito, T. Okada ,Y. Abe, Y. Kuromori, M. Miyashita, F. Iwata, M. Hara, M. Ayusawa, H. Mugishima, Y. Kitamura. Docosahexaenoic acid content in palasma phohpaolipids and desaturase indices in obese children. Journal of Atherosclerosis and Thromb 2011; 18. 000. [26] F. Dangardt, W. Osika, Y. Chen, U. Nilsson, L.M. Gan, E. Gronowitz, et al., Omega-3 fatty acid supplementation improves vascular function and reduces inammation in obese adolescents, Atherosclerosis 212 (2010) 580585. [27] A. Ambring, M. Johansson, M. Axelsen, L.M. Gan, B. Strandvik, P. Friberg, Mediterranean-inspired diet lowers the ratio of serum phospholipid n-6 to n-3 fatty acids, the number of leukocytes and platelets, and vascular endothelial growth factor in healthy subjects, American Journal of Clinical Nutrition 83 (2006) 575581. [28] M. Garemo, R.A. Lenner, B. Strandvik, Swedish pre-school children eat too much junk food and sucrose, Acta Paediatrica 96 (2007) 266272. [29] S.M.A. Donahue, S.L. Rifas-Shiman, D.R. Gold, Z.E. jouni, M.W. Gillman, E. Oken, Prenatal fatty acid status and child adiposity at age 3 y: results from a US pregnancy cohort, American Journal of Clinical Nutrition 93 (2011) 780788. [30] H. Mohrhauer, R.T. Holman, The effect of dietary essential fatty acids upon composition of polyunsaturated fatty acids in depot fat and erythrocytes of the rat, Journal of Lipid Research 4 (1963) 346350. [31] L.H. Lumey, A.D. Stein, E. Susser, Prenatal famine and adult health, Annual Review of Public Health 32 (24) 1-24.26. [32] B.S. Muhlhausler, R. Cook-Johnson, M. James, D. Miljkovic, E. Duthoit, R. Gibson. Opposing effects of omega-3 and omega-6 long chain polyunsaturated fatty acids on the expression of lipogenic genes in omental and retroperitoneal adipose depots in the rat. Journal of Nutrition and Metabolism, 2010; article ID927836, 9 pages, 10.1155/2010/927836. [33] F. Massiera, P. Barbry, P. Guesnet, A. Joly, S. Luquet, C. Moreilhon-Brest, T. Mohsen-Kanson, E.Z. Amri, G.A. Ailhaud, Western-like fat diet is sufcient to induce a gradual enhancement in fat mass over generations, Lipid Research 51 (2010) 23522361.

Birgitta Strandvik Unit of Public Health Nutrition, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden