In a recent review in the journal Open Heart, the official journal of the British Cardiovascular Society, researchers suggested that increased intake of the omega-6 polyunsaturated fat over the past several decades is largely responsible for the U.S. obesity epidemic .
One of the authors, James DiNicolantonio, is an associate editor of Open Heart, and has previously argued that saturated fat does not increase risk of coronary heart disease (CHD) [2, 3]. His co-author Artemis Simopoulos has been extolling the benefits of omega-3 fatty acids for over 30 years .
This recent review was met with some criticism from within the research community. In his online service Obesity and Energetics, David B. Allison, PhD, of the University of Alabama, referred to it as a “Narrative Review with Little Evidence of What Constitutes an ‘Evolutionary Fatty Acid Balance’ or Causal Evidence that It Would Affect Obesity” .
Obesity experts are in general agreement that there is no one single cause behind the obesity epidemic. Instead, a number of factors contribute to an obesogenic environment . Increased food availability and larger portion sizes are most likely part of the explanation contributing to the increase in calories consumed by Americans [7, 8.]. Americans also spend fewer hours sleeping, which may affect metabolism and hormonal balance and could stimulate appetite . The presence of environmental obesogens has also been suggested as a factor although this is very speculative .
In view of the complex nature of obesity, the theory put forward by Simopoulos and DiNicolantonio seems simplistic. They argue that humans evolved on a diet that had equal amounts of omega-6 and omega-3 fatty acids and that this 1:1 ratio promotes optimal health . It is more likely, however, that diets of prehistoric humans were more varied than commonly perceived and that they differed according to geographic location and food availability . Furthermore, optimal diets of early humans were those that supported reproduction and it is not clear that this is the same diet that would decrease chronic disease risk and improve longevity.
It is true however, that linoleic acid intake has increased dramatically over the past 100 years. According to disappearance data, the US omega-6 to omega 3 ratio is about 10:1 (Simopoulos and DiNicolantonio suggest that it is 16:1 but this is not supported by the data) . This ratio is no doubt a much higher ratio than that consumed by early humans . But whether the lower ratio is the preferred ratio for optimal health is much less clear. (Note that the work cited in support of 1:1 ratio being optimal for health is a review by Simopoulos ).
The Food and Agriculture Organization of the United Nations concluded in 2008 that there is no rationale for a specific recommendation regarding the ratio of omega-6 to omega-3 fatty acids as long as the omega-6 fatty acid intake is between 2.5% and 9% of energy and omega-3 fatty acid intake is between 0.5% and 2% of energy, allowing for a wide range of ratios . According to US food disappearance data, linoleic acid and alpha-linolenic acid intakes fall within these specifications as these two fatty acids represent 7.21% and 0.72% of energy intake, respectively . In 2009, the American Heart Association (AHA) supported a recommendation of an omega-6 polyunsaturated fat intake of at least 5 to 10 percent of energy in the context of other AHA lifestyle and dietary recommendations . Further, they concluded that to reduce omega-6 polyunsaturated intakes from their current levels would be more likely to increase than to decrease risk for CHD. Finally, in 2016, the Global Burden of Diseases Nutrition and Chronic Diseases Expert Group concluded that the optimal diet for reducing CHD derives approximately 12% of calories from linoleic acid, which is even higher than the current US intake .
In contrast, evidence supporting the coronary benefits of the long chain omega-3 fatty acids has waned in recent years and proposed benefits of particular dietary ratios of omega-6 to omega-3 fatty acids have been challenged [18, 19]. Support for the protective effects of omega-3 fatty acids against cancer is also relative unimpressive [20, 21].
Simopoulos and DiNicolantonio claim that a high dietary intake of omega-6 fatty acids leads to increases in white adipose tissue and chronic inflammation, which are the ‘hallmarks of obesity [22, 23]. However, the two references cited in support of these statements are reviews co-authored by Simopoulos that consist almost entirely of in vitro and animal data. Furthermore, the notion that a high dietary intake of linoleic acid promotes inflammation has largely been discredited.
Extensive research shows that increasing linoleic acid intake has little effect on endogenous levels of arachidonic acid, the omega-6 fatty acid from which the proinflammatory eicosanoids are synthesized. When analyzing the results of 11 different comparisons in humans, Rett et al.  found that when linoleic acid intake decreased by as much as 90%, there were no significant changes in plasma/serum phospholipid arachidonic acid content. Similarly, increases in dietary linoleic acid intake, by as much as 550%, were not significantly correlated with changes in plasma/ serum phospholipid arachidonic acid content. Linoleic acid intake probably does not increase arachidonic acid content because the estimated fractional conversion rate of linoleic acid to arachidonic acid is only 0.3% to 0.6% .
But what about the effects of consuming arachidonic acid, which is provided largely by chicken, eggs and beef, on inflammation? By bypassing the inefficient endogenous conversion of linoleic acid to arachidonic acid it is possible to raise tissue levels of the latter. Therefore, a high meat intake could be problematic. This may in fact be one explanation for the lower BMIs observed in vegans compared to non-vegetarians despite similar caloric intakes . Vegans consume no arachidonic acid (although even nonvegetarians consume less than one gram per day) . While such observations are provocative, the implications of consuming arachidonic acid remain unclear since it is now recognized that there appears to be a mix of both pro- and anti-inflammatory eicosanoids produced from this fatty acid . This may partially explain why extensive clinical research has failed to find pro-inflammatory effects of linoleic acid intake .
Furthermore, the difference in BMI between vegans and nonvegetarians is likely the result of many factors, including different protein sources. One study found that among 89,432 men and women from five countries participating in European Prospective Investigation into Cancer and Nutrition (EPIC) who were followed for a mean of 6.5 years, higher intake of protein from animal sources was associated with subsequent weight gain for both genders . However, an earlier comprehensive review of the epidemiologic data concluded on that levels of protein intake, regardless of source, are not associated with subsequent excess weight gain or obesity .
Simopoulos and DiNicolantonio note that in animal experiments, a high omega-6 fatty acid intake leads to decreased insulin sensitivity in muscle and promotes fat accumulation in adipose tissue. Obviously, conclusions based on animal experiments don’t rise above the level of speculation with respect to their applicability to humans. Furthermore, a recent meta-analysis involving 102 clinical trials and over 4,000 adults concluded that in comparison to carbohydrate, saturated fat or monounsaturated fat, omega-6 polyunsaturated fat favorably affects glycemia, insulin resistance, and insulin secretion capacity .
Finally, Simopoulos and DiNicolantonio claim that omega-3 fatty acids decrease adipose tissue development and lead to weight loss.[32-34] However, of the three references cited in defense of this claim, one was a mouse study , one a general review , and the third a meta-analysis that concluded “Current evidence cannot support an exact anti-obesity role of n-3 polyunsaturated fatty acids (PUFAs) in overweight/obese subjects” . While they also cited a study showing that high concentrations of omega-6 fatty acids in red blood cell membrane phospholipids were associated with an increased risk of weight gain in healthy women over a 10-year period, the findings have not been duplicated by other researchers . Furthermore, as noted by the authors of this study, there was only a single baseline measurement of erythrocyte fatty acid without assessment of any change over time. Also, the study used a convenient sample from a previous study that was not a priori designed, to test the hypotheses about erythrocyte fatty acid and weight gain.
In conclusion, many factors undoubtedly contribute to the worldwide obesity epidemic. The argument put forth by Simopoulos and DiNicolantonio that a high omega-6 linoleic acid intake is the primary cause behind the American epidemic is currently not supported by the evidence.
- Simopoulos, A.P. An increase in the omega-6/omega-3 fatty acid ratio increases the risk for obesity. Nutrients. 2016, 8, 128.
- Ravnskov, U., DiNicolantonio, J.J., Harcombe, Z., Kummerow, F.A., Okuyama, H., and Worm, N. The questionable benefits of exchanging saturated fat with polyunsaturated fat. Mayo Clin Proc. 2014, 89, 451-3.
- DiNicolantonio, J.J. The cardiometabolic consequences of replacing saturated fats with carbohydrates or Ω-6 polyunsaturated fats: Do the dietary guidelines have it wrong? Open Heart J. 2014, 1:e000032, 1.
- Simopoulos, A.P. and Salem, N., Jr. Purslane: a terrestrial source of omega-3 fatty acids. N Engl J Med. 1986, 315, 833.
- Obesity and Energetics Offerings. (2016, October 28). [Electronic Newsletter]. Retrieved from http://obesityandenergetics.org/weeklyofferings/102816
- Swinburn, B., Egger, G., and Raza, F. Dissecting obesogenic environments: the development and application of a framework for identifying and prioritizing environmental interventions for obesity. Prev Med. 1999, 29, 563-70.
- Vandevijvere, S., Chow, C.C., Hall, K.D., Umali, E., and Swinburn, B.A. Increased food energy supply as a major driver of the obesity epidemic: a global analysis. Bull World Health Organ. 2015, 93, 446-56.
- Swinburn, B., Sacks, G., and Ravussin, E. Increased food energy supply is more than sufficient to explain the US epidemic of obesity. Am J Clin Nutr. 2009, 90, 1453-6.
- Al Khatib, H.K., Harding, S.V., Darzi, J., and Pot, G.K. The effects of partial sleep deprivation on energy balance: a systematic review and meta-analysis. Eur J Clin Nutr. 2016,
- Holtcamp, W. Obesogens: an environmental link to obesity. Environ Health Perspect. 2012, 120, a62-8.
- Simopoulos, A.P. Evolutionary aspects of diet and essential fatty acids. World Rev Nutr Diet. 2001, 88, 18-27.
- Sayers, K. and Lovejoy, C.O. Blood, bulbs, and bunodonts: on evolutionary ecology and the diets of Ardipithecus, Australopithecus, and early Homo. Q Rev Biol. 2014, 89, 319-57.
- Blasbalg, T.L., Hibbeln, J.R., Ramsden, C.E., Majchrzak, S.F., and Rawlings, R.R. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr. 2011, 93, 950-62.
- Kuipers, R.S., Luxwolda, M.F., Dijck-Brouwer, D.A., Eaton, S.B., Crawford, M.A., Cordain, L., and Muskiet, F.A. Estimated macronutrient and fatty acid intakes from an East African Paleolithic diet. Br J Nutr. 2010, 104, 1666-87.
- Fats and fatty acids in human nutrition. Report of an expert consultation. Food and Nutrition Paper 91. Food and Agriculture Organization of the United Nations. Rome, 2010.
- Harris, W.S., Mozaffarian, D., Rimm, E., Kris-Etherton, P., Rudel, L.L., Appel, L.J., Engler, M.M., Engler, M.B., and Sacks, F. 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. 2009, 119, 902-7.
- Wang, Q., Afshin, A., Yakoob, M.Y., Singh, G.M., Rehm, C.D., Khatibzadeh, S., Micha, R., Shi, P., Mozaffarian, D., Ezzati, M., et al. Impact of nonoptimal intakes of saturated, polyunsaturated, and trans fat on global burdens of coronary heart disease. J Am Heart Assoc. 2016, 5,
- Colussi, G., Catena, C., Novello, M., Bertin, N., and Sechi, L.A. Impact of omega-3 polyunsaturated fatty acids on vascular function and blood pressure: Relevance for cardiovascular outcomes. Nutr Metab Cardiovasc Dis. 2016,
- Del Gobbo, L.C., Imamura, F., Aslibekyan, S., Marklund, M., Virtanen, J.K., Wennberg, M., Yakoob, M.Y., Chiuve, S.E., Dela Cruz, L., Frazier-Wood, A.C., et al. omega-3 polyunsaturated fatty acid biomarkers and coronary heart disease: Pooling project of 19 cohort studies. JAMA Intern Med. 2016, 176, 1155-1166.
- Song, M., Chan, A.T., Fuchs, C.S., Ogino, S., Hu, F.B., Mozaffarian, D., Ma, J., Willett, W.C., Giovannucci, E.L., and Wu, K. Dietary intake of fish, omega-3 and omega-6 fatty acids and risk of colorectal cancer: A prospective study in U.S. men and women. Int J Cancer. 2014, 135, 2413-23.
- Wu, S., Feng, B., Li, K., Zhu, X., Liang, S., Liu, X., Han, S., Wang, B., Wu, K., Miao, D., et al. Fish consumption and colorectal cancer risk in humans: a systematic review and meta-analysis. Am J Med. 2012, 125, 551-9 e5.
- Pisani, D.F., Ghandour, R.A., Beranger, G.E., Le Faouder, P., Chambard, J.C., Giroud, M., Vegiopoulos, A., Djedaini, M., Bertrand-Michel, J., Tauc, M., et al. The omega6-fatty acid, arachidonic acid, regulates the conversion of white to brite adipocyte through a prostaglandin/calcium mediated pathway. Mol Metab. 2014, 3, 834-47.
- Pisani, D.F., Amri, E.Z., and Ailhaud, G. Disequilibrium of polyunsaturated fatty acids status and its dual effect in modulating adipose tissue development and functions. OCL. 2015, 22, D405.
- Rett, B.S. and Whelan, J. Increasing dietary linoleic acid does not increase tissue arachidonic acid content in adults consuming Western-type diets: a systematic review. Nutr Metab (Lond). 2011, 8, 36.
- Demmelmair, H., Iser, B., Rauh-Pfeiffer, A., and Koletzko, B. Comparison of bolus versus fractionated oral applications of [13C]-linoleic acid in humans. Eur J Clin Invest. 1999, 29, 603-9.
- Orlich, M.J., Singh, P.N., Sabate, J., Jaceldo-Siegl, K., Fan, J., Knutsen, S., Beeson, W.L., and Fraser, G.E. Vegetarian dietary patterns and mortality in Adventist Health Study 2. JAMA Intern Med. 2013, 173, 1230-8.
- Rizzo, N.S., Jaceldo-Siegl, K., Sabate, J., and Fraser, G.E. Nutrient profiles of vegetarian and nonvegetarian dietary patterns. J Acad Nutr Diet. 2013, 113, 1610-9.
- Johnson, G.H. and Fritsche, K. Effect of dietary linoleic acid on markers of inflammation in healthy persons: A systematic review of randomized controlled trials J Acad Nutr Diet. 2012, 112, 1029-1041.
- Halkjaer, J., Olsen, A., Overvad, K., Jakobsen, M.U., Boeing, H., Buijsse, B., Palli, D., Tognon, G., Du, H., van der, A.D., et al. Intake of total, animal and plant protein and subsequent changes in weight or waist circumference in European men and women: the Diogenes project. Int J Obes (Lond). 2011, 35, 1104-13.
- Summerbell, C.D., Douthwaite, W., Whittaker, V., Ells, L.J., Hillier, F., Smith, S., Kelly, S., Edmunds, L.D., and Macdonald, I. The association between diet and physical activity and subsequent excess weight gain and obesity assessed at 5 years of age or older: a systematic review of the epidemiological evidence. Int J Obes (Lond). 2009, 33 Suppl 3, S1-92.
- Imamura, F., Micha, R., Wu, J.H., de Oliveira Otto, M.C., Otite, F.O., Abioye, A.I., and Mozaffarian, D. Effects of saturated fat, polyunsaturated fat, monounsaturated fat, and carbohydrate on glucose-insulin homeostasis: A systematic review and meta-analysis of randomised controlled feeding trials. PLoS Med. 2016, 13, e1002087.
- Li, J., Li, F.R., Wei, D., Jia, W., Kang, J.X., Stefanovic-Racic, M., Dai, Y., and Zhao, A.Z. Endogenous omega-3 polyunsaturated fatty acid production confers resistance to obesity, dyslipidemia, and diabetes in mice. Mol Endocrinol. 2014, 28, 1316-28.
- Martinez-Fernandez, L., Laiglesia, L.M., Huerta, A.E., Martinez, J.A., and Moreno-Aliaga, M.J. Omega-3 fatty acids and adipose tissue function in obesity and metabolic syndrome. Prostaglandins Other Lipid Mediat. 2015, 121, 24-41.
- Du, S., Jin, J., Fang, W., and Su, Q. Does fish oil have an anti-obesity effect in overweight/obese adults? A meta-analysis of randomized controlled trials. PLoS One. 2015, 10, e0142652.
- Wang, L., Manson, J.E., Rautiainen, S., Gaziano, J.M., Buring, J.E., Tsai, M.Y., and Sesso, H.D. A prospective study of erythrocyte polyunsaturated fatty acid, weight gain, and risk of becoming overweight or obese in middle-aged and older women. Eur J Nutr. 2016, 55, 687-97.