IMPACT OF SOYBEAN OIL ON METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE (MASLD) AND CARDIOMETABOLIC OUTCOMES

By Martha Anne Belury, PhD, RDN

Approximately one in four U.S. adults have metabolic dysfunction-associated steatotic liver disease (MASLD), formerly called non-alcoholic fatty liver disease (NAFLD), a condition that usually accompanies central obesity. NAFLD is tightly linked with hepatic insulin resistance and is therefore a major risk factor for metabolic syndrome and type 2 diabetes. It is mis-considered the “hepatic manifestation” for cardiometabolic diseases. Therapies that reduce ectopic liver fat (defined as an abnormal accumulation of fat within the liver, where fat is not typically stored in significant amounts) also reduce risk for cardiometabolic diseases; yet, other than weight loss, therapies that effectively and safely reduce ectopic lipid accumulation in the liver remain elusive.

Diets high in saturated fat or high fructose corn syrup are known to increase the risk of developing NAFLD. In contrast, diets rich in long chain omega-3 fatty acids have been tested for lowering liver fat but with varied success.¹ There is intriguing speculation that the essential omega-6 fatty acid linoleic acid (LA; 18:2n6) may retard lipid accumulation in the liver.² However, to our knowledge, there have not been any studies to determine if supplementing the diet with LA will therapeutically reduce fat content in the liver of people with NAFLD. Americans consume 7-8% of their energy intake from LA3,4 and the Dietary Guidelines for Americans recommends LA intake to be 5-10% of energy.⁵

Linoleic acid and health

Dietary LA intake is inversely associated with mortality in women⁶ and with risk of type 2 diabetes mellitus (T2DM) in adults.⁷ Also, blood biomarkers of LA intake are inversely correlated with total and coronary heart disease mortality,⁸ incidences of diabetes⁹ and NAFLD,¹⁰ visceral and liver fat,¹¹ and markers of inflammation.¹² LA biomarkers are positively associated with lean mass in men and women¹² and negatively associated with adipose accumulation in muscle of older adults.^13-16

Compared to a diet high in saturated fat, a diet high in LA has been shown to have beneficial effects in multiple studies.^17-21 In dietary intervention trials, supplementing the diet with a LA-rich oil increases lean mass¹⁵ and HDL-cholesterol,¹⁴ and decreases trunk fat,¹⁵ C-reactive protein (a marker of inflammation),¹⁴ glucose,^14,15 and the cardioprotective cytokine adiponectin.¹⁶ Adults who consumed a diet rich in LA saw improvements in insulin sensitivity and LDL-cholesterol when compared to the same adults who consumed a diet high in saturated fat.18 In healthy adults, a eucaloric diet rich in LA decreased fat mass, total cholesterol, and LDL-cholesterol after 16 weeks compared to a diet rich in saturated fat.²⁰

LA and liver health

In a study where abdominally obese adults consumed a 10-week isocaloric diet rich in LA vs. saturated fat, adults consuming the LA-rich diet had decreased liver fat accumulation and markers of inflammation which was not found in the saturated fat diet group.¹⁷ In agreement, in an overfeeding trial in which non-obese adults were fed muffins rich in saturated fat or rich in LA, there was an in increase in liver fat and visceral fat accumulation when consuming the former but not the latter.^19,21

Oil derived from conventional soybeans contains approximately 51-55% LA. Therefore, the many benefits of LA on body composition, lipoprotein metabolism, and insulin sensitivity strongly suggest that that LA-fortified diets using soybean oil will reduce hepatic lipid accumulation in people with MASLD. Studies to evaluate the role of soybean oil fortification of diets to reduce ectopic lipids in the liver are underway.

REFERENCES

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11. Rosqvist, F., Bjermo, H, Kullberg, J, Johansson, L, Michaëlsson, K, Ahlström, H, Lind, L, Risérus, U. Fatty acid composition in serum cholesterol esters and phospholipids is linked to visceral and subcutaneous adipose tissue content in elderly individuals: a cross-sectional study. Lipids Health Disease 16, doi:10.1186/s12944-017-0445-2 (2017).

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13. Reinders, I., Song, X, Visser, M, Eiriksdottir, G, Gudnason, V, Sigurdsson, S, Aspelund, T, Siggeirsdottir, K, Brouwer, IA, Harris, TB, Murphy, RA. Plasma phospholipid PUFAs are associated with greater muscle and knee extension strength but not with changes in muscle parameters in older adults. The Journal of nutrition. 145, 105-112 (2015).

14. Asp, M., Collene, AL, Norris, LE, Cole, RM, Stout, MB, Tang, SY, Hsu, JC, Belury, MA,. Time-dependent effects of safflower oil to improve glycemia, inflammation and blood lipids in obese, post-menopausal women with type 2 diabetes: a randomized, double-masked, crossover study. Clinical Nutrition 30, 443-449 (2011).

15. Norris, L., Collene, AL, Asp, ML, Hsu, JC, Liu, LF, Richardson, JR, Li, D, Bell, D, Osei, K, Jackson, RD, Belury, MA. Comparison of dietary conjugated linoleic acid with safflower oil on body composition in obese postmenopausal women with type 2 diabetes mellitus. Am J Clin Nutr 90, 468-476, doi:10.3945/ajcn.2008.27371 (2009).

16. Cole, R. M. et al. Linoleic Acid-Rich Oil Supplementation Increases Total and High-Molecular-Weight Adiponectin and Alters Plasma Oxylipins in Postmenopausal Women with Metabolic Syndrome. Curr Dev Nutr 4, nzaa136, doi:10.1093/cdn/nzaa136 (2020).

17. Bjermo, H., Iggman, D, Kullberg, J, Dahlman, I, Johansson, L, Persson, L, Berglund, J, Pulkki, K, Basu, S, Uusitupa, M, Rudling, M, Arner, P, Cederholm, T, Ahlström, H, Risérus, U,. Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial. Am J Clini Nutr. 95, 1003-1012 (2012).

18. Summers, L., Fielding, BA, Bradshaw, HA, Ilic, V, Beysen, C, Clark, ML, Moore, NR, Frayn, KN. Substituting dietary saturated fat with polyunsaturated fat changes abdominal fat distribution and improves insulin sensitivity. Diabetologia 45, 369-377 (2002).

19. Rosqvist, F., Iggman, D, Kullberg, J, Cedernaes, J, Johansson, HE, Larsson, A, Johansson, L, Ahlström, H, Arner, P, Dahlman I, Risérus, U. Overfeeding polyunsaturated and saturated fat causes distinct effects on liver and visceral fat accumulation in humans. Diabetes 63, 2356-2368 (2014).

20. Stonehouse, W. et al. Eucaloric diets enriched in palm olein, cocoa butter, and soybean oil did not differentially affect liver fat concentration in healthy participants: a 16-week randomized controlled trial. Am J Clin Nutr 113, 324-337, doi:10.1093/ajcn/nqaa347 (2021).

21. Rosqvist, F., Kullberg, J, Ståhlman, M, Cedernaes, J, Heurling, K, Johansson, HE, Iggman, D, Wilking, H, Larsson, A, Eriksson, O, Johansson, L, Straniero, S, Rudling, M, Antoni, G, Lubberink, M, Orho-Melander, M, Borén, J, Ahlström, H, Risérus, U. Overeating Saturated Fat Promotes Fatty Liver and Ceramides Compared With Polyunsaturated Fat: A Randomized Trial. J Clin Endocrinol Metab 104, 6207-6219 (2019).