Sweet, Sweet Fructose

Posted by Xi Jiang on May 12, 2016 in Neuroscience, Social Psychology | Leave a comment

When a cat licks you (lucky you), have you ever considered licking back? (Some have.) If you have, and did, you would have noticed that cats do not taste sweet. Nevertheless, phrases such as “sweet kittens” and “sweet deals”, alongside terms like “sweetheart”, pervade the modern English language; “sweet”, like “nice”, “awesome”, and “cool”, has become a catch-all word of appreciation for any pleasant stimulus. As the developed world becomes increasingly health-conscious, however, the reputation of sugar is suffering from the prevalence of added sugar in commercial food products. In 2009, the American Heart Association issued a warning against excessive sugar intake (see this NeuWrite infographic on the effects thereof), citing an observed link between obesity and added sugar consumption [1]. Now, we already know sugar to be an important contributor of food energy. Could it be as simple as “we get fat because we eat more”, or is there more to “added sugar” than its sweetness?

In the United States, the most popular types of added sugar are sucrose (i.e. table sugar) and high-fructose corn syrup, both primarily composed of about half glucose and half fructose [2]. While both glucose and fructose are sweet molecules called monosaccharides (“single-sugars”, the simplest form of carbohydrates), their differences are more than cosmetic.

Sucrose is just a glucose/fructose couple holding hands. How sweet!

Utilized by everything from bacteria to humans, found in potatoes and duck livers alike—glucose is as ubiquitous as it is important. It is the primary energy supplier for our brains [3], and when we talk about “blood sugar”, glucose is usually what we mean. When it comes to sweetness, though, fructose, not glucose, is the  “better” half of sucrose.

Fructose, or “fruit sugar” in colloquial German [4], is obtained from plants, such as corn, sugarcane, and various orchard plants. Fructose is often found as part of sucrose (see figure above). When we eat food that contains fructose, either as single-sugar or as half-of-sucrose, our bodies process it differently from how we usually deal with glucose. Both glucose and fructose, after becoming single sugars again (with the help of intestinal enzyme), eventually become G3P—the awkward teenage phase of energy metabolism—before actually making a difference in the energy-extracting Krebs cycle. Fructose relies on enzymes in the liver to begin its transformations, while glucose does not [5]. As one might expect, it takes longer to digest one unit of fructose than one unit of glucose [6].

At this point, an astute reader may have begun to wonder if, given the differences in biochemical processing, there is a significant difference between fructose and glucose in terms of health impact. Now that, quite literally, is the million-dollar question. Sugar has been lucrative since the time of the Silk Road, and it has certainly remained so; just four years ago, the U.S. food industry relied on sugar for more than 70% of unique commercial products [7]. With somewhat counterproductive measures of fear-mongering, some blame the “artificial”-ness of certain sweeteners such as high-fructose corn syrup for the connection between sugar consumption and health issues. Others proclaim themselves against the “artificial equals unhealthy” irrational bias, and defend said sweeteners staunchly, citing the omnipresence of equivalent fructose proportions in all forms of sugar-containing sweeteners, be it cane sugar or juice concentrate [6, 8]. And the defenders do have a point: a recent survey study conducted in Switzerland found that, given two otherwise identical boxes of sugar-containing breakfast cereal, the box with its label calling sugar “fruit sugar” was overwhelmingly judged to be more healthy [4].

One is just as (un)healthy as the other, the green bowl notwithstanding.

Even the defenders of high-fructose corn syrup, however, agree that studies examining the effect of fructose itself show negative correlations, especially at high concentrations [6, 8]. By inference, one might expect that an increase in daily sugar intake, half of which is likely to be fructose, would significantly impact metabolic health, obesity included. Unlike glucose, fructose metabolism has a tendency to “dampen” activity in the hypothalamus, a brain structure crucial to appetite regulation with hormone- and glucose-sensing neurons, leading to increased food intake [9]. Fructose also does not promote the secretion of insulin, a hormone that signals the brain to increase satiety and reduce the reward value of food [10]. In a 2015 study, twenty-four human volunteers underwent functional magnetic resonance imaging (fMRI) sessions upon ingestion of either fructose or glucose (75g, or about half the amount of expected sucrose in four medium blueberry muffins) [11]. Volunteers viewed images of food and non-food items during each fMRI session. They were given a choice between having food reward immediately or waiting for monetary reward at the end of all sessions. The fructose group was more likely to seek immediate food reward, and had greater activation in response to food cues over the occipital cortex (visual stimuli processing), as well as the left orbitofrontal cortex (decision-making).

Unfortunately, fructose’s effect on appetite may only be the tip of a very ugly iceberg. Just last month (Apr. 2016), an international collaborative study with rodent models on the effect of common nutrients over gene networks in the brain was published online [12]. The authors claimed to have revealed fructose’s capacity “to reorganize gene networks critical for central metabolic regulation and neuronal processes in the brain.” Specifically, they showed that rats on a fructose-rich diet displayed memory deficits, and captured gene expression profiles of said rats. They then altered gene expression in regular-diet mice models to match the changes observed in fructose-fed rats. The altered mice produced physiological signatures consistent with key parameters of obesity, such as decreased insulin level and elevated free fatty acids [13]. The authors, therefore, concluded that fructose could induce metabolic and behavioral abnormalities in rodents, and they suggested that DHA, a compound often found in seafood, partially reverses the observed effect of fructose.

Should we all eat fish instead of fruit (or blueberry muffins, for that matter) from now on? Probably not because of a single study, no matter how prestigious the authors. One might even wonder if there is any point to this whole article at all, if the simple solution of “eating less sugar” is all it takes to avoid excessive fructose. It is perhaps worth mentioning, therefore, that there are people who either have no choice or are not informed well enough about their choices. In the United Kingdom, for example, a government survey in 2011 found that “those on low income…tended to drink more soft drinks (not diet drinks) and eat more processed meats, whole milk and sugar.” The same survey reported that people with a lower level of educational achievement tended to have a ‘less healthy’ diet than those with more education, and that ~30% of all respondents considered price the most important factor for food purchases. Similarly, in the U.S., a survey study on ~3000 subjects from the state of Washington found that people with annual income over US$75,000 were nearly twice as likely to report using calorie information (much of which due to sugar presence) compared to those making less than US$35,000 yearly [14]. For those of us who can make an effort to evaluate evidence and inform others, then, it would be good to actually do so.

References:

[1] Johnson, R. et al., (2009) Dietary sugars intake and cardiovascular health: a scientific statement from the American Heart Association. Circulation, 120(11), 1011-1020.

[2] Welsh, J., Sharma, A., Grellinger, L., Vos, M. (2011). Consumption of added sugars is decreasing in the United States. Am J Clin Nutr, 94(3), 726–734.

[3] Berg, J., Tymoczko, J., Stryer, L. Biochemistry. 5th ed. New York: W.H. Freeman, 1988. NCBI Bookshelf. Web. 4 May 2016.

[4] Sütterlin, B. & Siegrist, M. (2015). Simply adding the word “fruit” makes sugar healthier: The misleading effect of symbolic information on the perceived healthiness of food. Appetite, 95, 252-261.

[5] Ouyang, X. et al. (2008). Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J. Hepatol., 48(6), 993–999.

[6] Ludwig, D. (2013). Examining the health effect of fructose. JAMA, 310(1), 33-34.

[7] Ng, S., Slining, M., Popkin, B. (2012). Use of caloric and noncaloric sweeteners in US consumer packaged foods, 2005-2009. J Acad Nutr Diet, 112(11), 1828-1834.

[8] White, J. (2008). Straight talk about high-fructose corn syrup: what it is and what it ain’t. Am J Clin Nutr, 88(6). 1716S-1721S.

[9] Cha, S., Wolfgang, M., Tokutake, Y., Chohnan, S., Lane, M. (2008). Differential effects of central fructose and glucose on hypothalamic malonyl-CoA and food intake. Proc Natl Acad Sci USA, 105(44), 16871–16875.

[10] Figlewicz, D., Benoit, S. (2009). Insulin, leptin, and food reward: Update 2008. Am J Physiol Regul Integr Comp Physiol, 296(1), R9–R19.

[11] Luo, S. et al. (2015). Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards. Proc Natl Acad Sci USA, 112(20), 6509-6514.

[12] Meng, Q. et al. (2016). Systems nutrigenomics reveals brain gene networks linking metabolic and brain disorders. EBioMedicine, Corrected Proof on Apr. 13th.

[13] Boden, G. (2008). Obesity and free fatty acids (FFA). Endocrinol Metab Clin North Am, 37(3), 635-ix.

[14] Chen, R. et al. (2015) Changes in awareness and use of calorie information after mandatory menu labeling in restaurants in King County, Washington. Am J Public Health,105(3), 546–553.