Ever since the YouTube video of Dr. Lustig and the evils of fructose went viral in 2010, many have advocated that fructose is the single most common cause of obesity in the United States.
The video had metabolic pathways that had the hypothesis that most fructose either becomes fat in the liver, or that it might go down a pathway to cause joint issues, leaky gut, and inflammation causing obesity.
Here are the two chemical structures of glucose, also known as the "good sugar" and fructose, or the bad sugar. I cannot help but thinking of the good witch and the bad witch on the Wizard of Oz.
Dr. Lustig's hypothesis was based on studies done in mice and rats. In those studies, published two years before the viral video, found that high fructose diets in mice lead to increased "gut leak" and led to liver damage (1). This was even confirmed with a small study of 8 men (2) who had their complex carbohydrates replaced by fructose and fed normal caloric diets - meaning, these eight men had increased liver fat, more de novo fat formation (de novo lipogenesis) .
This all makes that logical sense since sugar-sweetened beverages are associated with chronic inflammation and these days everything to do with chronic inflammation increases the risk of obesity, diabetes, heart disease, and aging.
Then came a double-blinded, randomized, crossover study where a group of people were fed a standard diet but drank 25% of their calories as either fructose (the evil sugar), or glucose (the good one) or a high fructose corn syrup sweetened beverage. Oddly, there was no difference in any of those groups with regard to markers of inflammation, intestinal permeability, or inflammation in the fat tissue.
To quote from the study: "Excessive amounts of fructose, HFCS, and glucose from SSBs consumed over 8 d did not differentially affect low-grade chronic systemic inflammation in normal-weight to obese adults." SSB = sugar sweetened beverages.
There have been a number of human trials looking at sugar-sweetened beverages and inflammation, and the results are not consistent. Even finding that people who drink large amounts of either glucose of fructose didn't find changes in inflammation or visceral fat.
Mice are not men, and the link between gut permeability, leading to systemic and chronic inflammation, occurs in mice, but not men. And while in mice fructose can lead to inflammation and liver issues, this doesn't happen in human beings. (4)
The key may not be fructose itself, but increased caloric intake. If you eat more, you will increase in weight, but it is not fructose alone. It is, in fact, high caloric intake combined with sugars. Meaning, that great tasting snack with the high levels of sugars and fats act in concert with the increased calories consumed to give you that portly look.
To be fair, all of the studies were short term, less than a couple of weeks. Fructose, over the long term, may still be a bad actor.
What about fruit? It is exceedingly difficult to eat enough whole fruits to make this a problem. To eat the excess amount in some of these studies you would have to eat several pounds of apples, and most people simply cannot do that in a day. And whole fruit consumption, as a part of the Mediterranean diet reduces the burden of cardiovascular disease, diabetes, and even erectile dysfunction.(5)
In fact less than 10% of most Western dieters have adequate levels of fruit (6) leading to a serious threat to human health. Maybe a couple of apples a day will keep the doctor away.
(1) Bergheim I, Weber S, Vos M, Krämer S, Volynets V, Kaserouni S, McClain CJ, Bischoff SC. Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin. J Hepatol. 2008 Jun;48(6):983-92. doi: 10.1016/j.jhep.2008.01.035. Epub 2008 Mar 14. PMID: 18395289.
(2) Schwarz JM, Noworolski SM, Wen MJ, Dyachenko A, Prior JL, Weinberg ME, Herraiz LA, Tai VW, Bergeron N, Bersot TP, Rao MN, Schambelan M, Mulligan K. Effect of a High-Fructose Weight-Maintaining Diet on Lipogenesis and Liver Fat. J Clin Endocrinol Metab. 2015 Jun;100(6):2434-42. doi: 10.1210/jc.2014-3678. Epub 2015 Mar 31. PMID: 25825943; PMCID: PMC4454806.
(3) Kuzma JN, Cromer G, Hagman DK, Breymeyer KL, Roth CL, Foster-Schubert KE, Holte SE, Weigle DS, Kratz M. No differential effect of beverages sweetened with fructose, high-fructose corn syrup, or glucose on systemic or adipose tissue inflammation in normal-weight to obese adults: a randomized controlled trial. Am J Clin Nutr. 2016 Aug;104(2):306-14. doi: 10.3945/ajcn.115.129650. Epub 2016 Jun 29. PMID: 27357093; PMCID: PMC4962158.
(4) Chung M, Ma J, Patel K, Berger S, Lau J, Lichtenstein AH. Fructose, high-fructose corn syrup, sucrose, and nonalcoholic fatty liver disease or indexes of liver health: a systematic review and meta-analysis. Am J Clin Nutr. 2014 Sep;100(3):833-49. doi: 10.3945/ajcn.114.086314. Epub 2014 Aug 6. PMID: 25099546; PMCID: PMC4135494.
(5) Widmer RJ, Flammer AJ, Lerman LO, Lerman A. The Mediterranean diet, its components, and cardiovascular disease. Am J Med. 2015 Mar;128(3):229-38. doi: 10.1016/j.amjmed.2014.10.014. Epub 2014 Oct 15. PMID: 25447615; PMCID: PMC4339461.
(6) Dreher ML. Whole Fruits and Fruit Fiber Emerging Health Effects. Nutrients. 2018 Nov 28;10(12):1833. doi: 10.3390/nu10121833. PMID: 30487459; PMCID: PMC6315720.