sign in sign up
<<
Home , Disaccharide

Mānoa Horizons

Volume 4 | Issue 1 Article 12

9-20-2019 A Sweet State of Mind: The ffecE ts of High Corn on the Brain Lauryn Liao University of Hawaiʻi at Mānoa

Follow this and additional works at: https://kahualike.manoa.hawaii.edu/horizons Part of the Nutrition Commons

Recommended Citation Liao, Lauryn (2019) "A Sweet State of Mind: The Effects of High Fructose on the Brain," Mānoa Horizons: Vol. 4 : Iss. 1 , Article 12. Available at: https://kahualike.manoa.hawaii.edu/horizons/vol4/iss1/12

This Article is brought to you for free and open access by Kahualike. It has been accepted for inclusion in Mānoa Horizons by an authorized editor of Kahualike. For more information, please contact [email protected]. A Sweet State of Mind The Effects of High Fructose Corn Syrup on the Brain

Lauryn Liao

Honors 101 (Introduction to Research and Creative Work at Mānoa) Mentor: Dr. Zoia Stoytcheva

As both a palatable treat and necessary in moderation, is a highly prized substance present in the majority of and drinks. However, consumed in excess, sugar is known to have adverse health effects which can infringe on an individual’s qual- ity of life. This article aims to address and analyze the effect of sugar, specifically high fructose corn syrup, on the brain. Through the gut-brain-axis, from digested can directly reach the brain. In other words, an individual’s diet may impact his or her mental health. This concept of brain function and health in relation to what is con- sumed prompts many to wonder about the short and long-term effects sugar consumption has on the brain. Thus, studies have found evidence to support a correlation between excess sugar consumption and an increased risk for the development of neurodegenera- tive, psychological, and metabolic disorders including Alzheimer’s and Type 2 diabetes.

manufacturers around the globe. From TV dinners to salad Introduction dressings to cold cuts, HFCS has become an essential part of the daily American diet. However, this begs the question of Imagine a bottle of Coke, a can of Campbell’s Tomato Soup, how consuming this additive in food affects one’s behavior and and a loaf of bread. What do these have in common besides overall health. Moreover, sugar consumption and sodium? If you guessed sugar, you would be partially correct. in the gut has been linked to a variety of psychological and neu- These three typical supermarket items all contain high fruc- ro-degenerative diseases as well as metabolic syndrome disor- tose corn syrup, a specific type of processed sweetener. If this is ders [1]. This, in turn, prompts investigation on how high sugar surprising, then take a look down the aisles of your local Target consumption affects the neurological pathways in the brain. or Walmart and count how many foods and drinks contain this are simple that include monosac- additive. charides and disaccharides. are the building Since its humble introduction in the 1950’s, high fructose blocks of disaccharides and , which are com- corn syrup, or HFCS, has gained the favor of food and drink plex sugar molecules. In supermarkets, the most common

This paper was written for the Honors 101 class instructed by Dr. Zoia Stoytcheva. I am a University of Hawai‘i freshman majoring in Biological Engineering with the aim of becoming a physician. I believe college is a crucial time for personal growth, and a part of that is learning how to take care of yourself. One day, I found myself eating out of a bag of , wondering what effect a high-sugar diet like mine would have on my long-term health. Even with that thought in mind, I kept shoveling the sweets. However, as I researched and wrote this paper, I began to recognize the many draw- backs to consuming the widely available and oh-so-delicious processed sugars. Taking care of what is around you is easy, but taking care of what is inside of you will ultimately determine your quality of health and life. While I do not see an end to people loving their sweets, I can raise awareness of the amount we consume.

Mānoa Horizons, Vol. 4, 2019, pp. 85–89 Copyright © 2019 by the University of Hawai‘i at Mānoa 85

Manoa Horizons 4 Online.indb 85 9/9/2019 11:23:26 PM 86 Mānoa Horizons Vol. 4, Fall 2019

monosaccharides are and fructose; both of which con- vary. This suggests that diet plays a crucial role in the makeup stitute the disaccharide known as , or table sugar. of the host gut microbiota [3]. Therefore, since the gut micro- Derived from corn , HFCS is a manufactured biota aids in energy metabolism and of nutrients, the sweetener with the of glucose and fructose. While materials consumed by the host will be processed to the ability corn syrup processed from corn starch contains a high con- of the specific bacteria that compose the microbiota. centration of glucose, manufacturers of HFCS use an A large portion of the sugar consumed in the daily diet called glucose isomerase to convert a portion of the glucose comes from fructose, sugar found naturally in fruits and into fructose, which is a much sweeter sugar. ­. With modern technology, scientists developed a way to The prevalence of HFCS in the modern diet points to the manufacture high-fructose sweeteners from cash crops such possibility of health risks in later life. Thus far, research has as corn. A popular example of this sweetener is HFCS. linked sugar consumption with various diseases such as dia- To make HFCS, an enzyme is added to regular corn syr- betes, dementia, and even addiction. Moreover, scientists have up. This enzyme is known as glucose isomerase, and it con- also found that different sugars affect the brain differently. verts a portion of the glucose into fructose. According to the This article aims to identify how sugar affects the brain, behav- Food and Drug Administration (FDA), the most commonly ior, and the risk for disease through the interactions between used commercial forms of HFCS contain 42 or 55 percent the gut, brain, and body. fructose [5]. When compared to the amount of fructose con- tent in a single peach, which is about one percent of its entire weight, the fructose content in HFCS accounts for half of the Sugar, the GI tract, and the body compound’s total weight [6]. While consumption of fructose through fruits is supplemented by other nutrients such as fiber Any sweet-tasting, soluble is considered a sugar and vitamins, additive sugars like HFCS reside in foods which by definition. Sugar, or more specifically glucose, is the body’s are less nutritionally beneficial. For example, sodas and condi- main source of energy. The process of breaks down ments are high in natural and additive sugars, but they have glucose molecules into , which is an little nutritional gains to balance it out. (Fig.1) [7]. Comparison energy molecule, and pyruvic acid. Glycolysis is the first of of the sugar content among various food and drink items sold four processes of which in turn generate at Target in Salt Lake, Oahu are listed in Table 1. These items— the energy to fuel the necessary biological activities needed to which all contain HFCS as an ingredient—are also commonly sustain life. sold on school campuses and in other supermarkets around While plants can generate their own glucose by means of the island. , animals rely on food to supply glucose to the The gut-microbiota does not process all sugars the same cells. Depending on the type of food consumed, the amount of way. This means there are various ways sugar can be processed expendable glucose for cellular use varies. An effect of eating in the body. Although fructose is similar in chemical structure foods with high glucose turnover is elevated blood glucose lev- to sucrose, studies show that the different sugars take different els which, mean there is an above average amount of glucose metabolic pathways, meaning fructose is metabolized differ- in the bloodstream. For example, consuming carbohydrates ently from glucose [7]. The primary for glu- yields one hundred percent glucose for the body to use. There- cose involves cellular respiration, which produces adenosine fore, blood sugar levels become elevated shortly after inges- tion. On the other hand, meats and fats provide significantly less amounts of glucose, which cause little to no increase in blood sugar levels [2]. The human body is programmed to receive and process glucose, which is a of sugar disaccharides like su- crose and . Therefore, once the food is ingested, the job of the gut-microbiota is to break it down into molecules the body can use [3]. The gut-microbiota can be seen as the millions of bacteria that reside in the gastrointestinal tract (GI tract). These bacteria help support and maintain gut ho- meostasis which has direct effects on immune and epithelial Figure 1 Selection of Items Containing HFCS in Local Super- function in the lining of the GI tract [4]. Studies have proven market (Target in Salt Lake, Oahu. (A) Drinks containing sig- that the composition of the microbiota is affected by environ- nificant amounts of HFCS. (B) Sweet Baby Ray’s Original BBQ mental factors rather than an inherent set of bacteria present Sauce has HFCS as its number one ingredient, meaning it con- from birth [3]. Thus, depending on the food one consumes, the tains more HFCS than any other ingredient by volume. (C) Lo- types of bacteria that make up his or her gut-microbiota will cally made Love’s King White bread contains 2g sugar per slice.

Manoa Horizons 4 Online.indb 86 9/9/2019 11:23:26 PM Liao A Sweet State of Mind 87

Table 1 Sugar content in various foods and condiments containing HFCS. Food compound Total Sugars Serving Size on in grams per: Nutrition Label Condiments tablespoon Serving size Heinz Tomato Ketchup 4 4 1 tbsp Heinz Sweet Relish 3 3 1 tbsp Sweet Baby Ray’s BBQ Sauce 8 16 2 tbsp Market Pantry BBQ Sauce 8.5 34 ¼ cup Market Pantry Creamy French Dressing 3 6 2 tbsp Smucker’s Goober Grape Spread 7 21 3 tbsp Drinks ounce 12 oz can of Mountain Dew 3.8 46 1 can 16 oz can of Mountain Dew Kickstart 1.25 20 1 can 12 oz can of Coca-Cola 3.25 39 1 can Food Strawberry Pop-Tart 0.11 16 1 pastry (50g or 1.76 oz) 10.75 oz can of Campbell’s Condensed Tomato Soup 3 12 ½ cup (4 oz) 10.75 oz can of Campbell’s Condensed Vegetable Soup 1.5 6 ½ cup (4 oz) Love’s King White Bread 1.33 2 1 slice (2/3 oz)

* Variety List of popular foods and drinks (selected) from Target Salt Lake, Oahu. The values in the column “Total Sugars in grams per:” were calculated by taking the amount of sugar in one serving size and dividing it by the serving size. From this table, a com- parison can be made among common foods and condiments and the different amounts of sugar in one serving size.

triphosphate (ATP) to drive other metabolic processes. How- Because changes in the gut-microbiota directly affect the ever, the bulk of fructose metabolism occurs in the liver and integrity of the GI tract, studies have found an association be- kidneys. These pathways require fructose-specific transport tween intestinal permeability and certain diseases such as celi- proteins such as ketohexokinase (KHK) and aldolase. Certain ac disease and multiple organ dysfunction syndrome [8,9,10]. regions in the brain express the same genes present in kid- Though a controversial topic in the medical world, increased neys to metabolize fructose. Researchers also found that KHK permeability of the intestinal tract, referred to as “leaky gut and aldolase were 5-10 times more active in the brain, rather syndrome,” allows bacterial metabolites and byproducts to than in the liver. This suggests the possibility that fructose can leak into systemic circulation [11]. This causes the host to be reach the brain in order to be used for energy production [1]. vulnerable to diseases like inflammatory bowel disease (IBD) and diabetes as well as a number of psychiatric disorders [8,11]. While most medical professionals do not consider leaky The gut-brain-axis gut to be a condition, there have been numerous studies citing a relationship between intestinal permeability and susceptibil- The gut-brain-axis is a bidirectional communication system ity to disease. A study conducted on rats aimed to establish a that links the central nervous system (CNS) and the gastroin- link between host susceptibility to chemically-induced­ colitis, testinal tract which houses the gut-microbiota. The gut, brain, a specific type of IBD which affects the large intestine, and and body interact through this system. Therefore, anything high sugar diets. The scientists concluded high-sugar diets in- entering the gut has the potential to influence our cognitive crease host susceptibility to colitis in rats [12]. A second study activity and brain responses. investigated the effect of high fructose diets on intestinal Considering the interrelatedness between the gut and the permeability and the development of nonalcoholic fatty liver brain, certain neurological disorders and diseases have been disease (NAFLD). The study found that high fructose con- associated with an unhealthy diet, primarily those that contain sumption may lead to bacterial overgrowth in the intestine, high amounts of sugar [4]. These disorders include but are causing increased intestinal permeability and risk for devel- not limited to anxiety, depression, Alzheimer’s disease, and opment of NAFLD [13]. Therefore, although these studies have diabetes [8,4]. Furthermore, when an individual experiences been limited to rodent subjects, they emphasize the idea that dietary variation, the human microbiome will adjust to those the effects of high-sugar diets may extend beyond the associ- alterations. ated neurological disorders.

Manoa Horizons 4 Online.indb 87 9/9/2019 11:23:26 PM 88 Mānoa Horizons Vol. 4, Fall 2019

chological effects of ingesting this form of sugar. While the Sugar “Addiction” FDA makes no claims against the consumption of HFCS, the organization recommends consuming the additive sweet- The neurons in the brain, which are cells that relay signals ener in moderation [5]. Although this claim is substantiated throughout the body, require an enormous amount of energy by evidence that HFCS is not a toxic substance, the World to function properly. Therefore, these cells rely on a continu- Health Organization (WHO) reduced their recommended ous flow of energy which, in turn, makes the brain consume daily intake to less than 5% of all caloric intake about twenty percent of all glucose-derived energy [16]. While [18]. This puts a tough limit on the amount of added sugar there is extensive research on the direct effect of glucose on the consumed since a large amount of foods and drinks contain brain, little is known about the effects of fructose. excessive amounts of HFCS and other artificial sweeteners. Thus far, there have been studies conducted on rodents One study catalogued the HFCS content in popular sodas and that indicate there are detrimental side effects of high-sugar di- juices consumed by the public. The scientists found that the ets, specifically those composed of high-fructose [12,15]. Since most popular sodas such as Coke, Pepsi, Sprite, and Moun- the gut-brain-axis allows digested nutrient monomers to inter- tain Dew have a 60:40 fructose to glucose ratio. Moreover, act with the brain and nervous system, high sugar diets have they discovered that not only do fruit juices contain similar the potential to play a direct role in the onset of neurodegener- ratios, but some contain even higher fructose levels than the ative, psychological, and metabolic diseases. In 2018, a study total fructose content in sodas [19]. Currently, the American conducted on rats linked the consumption of HFCS to neuro- Heart Association recommends consuming less than 100 cal- nal hyperexcitability, a behavior normally associated with bipo- ories of sugar per day for women and less than 150 calories lar disorder [15]. Furthermore, a study conducted on patients per day for men [20]. Since one gram of sugar is equivalent with Type 2 Diabetes (T2D), a form of the metabolic disorder to four calories, this means about 25 grams and 37.5 grams known as diabetes that is associated with insulin resistance, respectively. To put this in context, a 12-ounce bottle of Coke concluded impairment of insulin signaling increases the per- exceeds an individual’s entire daily recommended sugar in- son’s risk of developing dementia [4]. However, although there take by about 14 grams for women and 1.5 grams for men. In is substantial evidence of a correlation between increased conclusion, these drinks alone, which are widely consumed sugar consumption and a higher risk of disease development, by kids and adults alike, make a substantial contribution to Americans continue to consume it in excess on a daily basis. the daily added sugar intake. The answer to America’s insatiable sugar cravings may A common misconception about increased sugar con- lie in the science behind addiction, which is broadly charac- sumption is that it only leads to obesity. However, because terized by dependence on a substance or habit. While sugar is of the gut-brain-axis, the effects of sugar on overall health unlike typical addictive substances such as nicotine or heroin, extend further than that. Although Alzheimer’s and diabe- studies show that rats demonstrate addiction-like behaviors on tes may be consequences of long-term excessive sugar con- sugar diets [16]. One study in particular found that when ro- sumption, the short-term consequences begin with cognitive dents predisposed to sugar addiction went on a sugar diet, they impairment accompanied by a stifled learning capability [21]. began exhibiting signs of addiction to the substance at around Although a majority of studies have been limited to rodent three to four weeks [17]. In these studies, sugar consumption observations and tests, the findings should raise awareness of leads to opioid and dopamine (DA) release in the brain. These the potential consequences of a high-sugar diet if consump- findings produce the idea of a shared neurobiology between tion is not limited. actual drugs and sugar [16]. However, because these studies People need to be more aware of what they put into have been limited to rodent subjects, researchers are limited their bodies. Sugar, both the natural and additive types, is to inferences in order to examine how sugar addiction displays found in everything regardless of whether it can be tasted itself in humans. Therefore, the idea of whether or not sugar or not. Moreover, the United States is the world’s leading is an addictive substance, rather than one that produces only per-capita consumer of HFCS [13,22]. This is further accom- similar habits when consumed, is a controversial topic. More panied by rising rates of obesity. Therefore, research needs to be conducted on the correlation between intake by opting for ‘unsweetened’ or ‘low sugar’ alternatives sugar content and addictive potential as well as the effect of would be an effective preventative step towards reducing prolonged sugar consumption in animals. risks for diabetes, Alzheimer’s, obesity, and other disor- ders. While the phenotypic effects of these diseases usually present themselves after prolonged accumulation of various Discussion/Conclusion substances including sugar, this information about the in- terrelatedness between food, the brain, and the body allows Considering the prevalence of HFCS in the American diet, individuals to make better decisions when it comes to their consumers need to be aware of the neurological and psy- sugar consumption.

Manoa Horizons 4 Online.indb 88 9/9/2019 11:23:26 PM Liao A Sweet State of Mind 89

American Gastroenterological Association, 11(9), 1075–1083. Works cited https://doi.org/10.1016/j.cgh.2013.07.001 [12] Fedorak, R., Ginter, R., Keshteli, A.H., Agrawal, A., Hotte, [1] Oppelt, S.A., Wanming, Z., & Tolan, D.R. (2017, February N., & Madsen, K.(n.d.). 263 Fecal Microbial Transplan- 15). Specific Regions of the Brain are Capable of Fructose tation Can Modulate Increased Colitis Susceptibility Metabolism. Retrieved October 1, 2018, from https:// Induced by High Sugar Diets- ClinicalKey. Retrieved www​-clinicalkey-com.eres.library.manoa.hawaii.edu​ October 3, 2018, from https://www-clinicalkeycom.eres​ /#!​/­content​/playContent/1-s2.0-S0006899316308435​ .­library​.manoa.hawaii.edu/#!/content/playContent​/1-s2​ ?returnurl­ =null&referrer=null​ .0​-S0016508515302080?returnurl=null&referrer=null [2] Thursby, E., & Juge, N. (2017). Introduction to the human [13] Spruss, A., & Bergheim, I. (2009). Dietary fructose and in- gut microbiota. Biochemical Journal, 474(11), 1823–1836. testinal barrier: potential risk factor in the pathogenesis of https://doi.org/10.1042/BCJ20160510 nonalcoholic fatty liver disease. The Journal of Nutritional [3] Cresci, G.A., & Bawden, E. (2015). Gut Microbiome. Nutri- , 20(9), 657–662. https://doi.org/10.1016/j​ tion in Clinical Practice, 30(6), 734–746. https://doi.org​/10​ .jnutbio​.2009.05.006 .1177​/0884533615609899 [14] Mergenthaler, P., Lindauer, U., Dienel, G.A., & Meisel, A. [4] Moreira, P.I. (2013). High-sugar diets, type 2 diabetes and (2013). Sugar for the brain: the role of glucose in physi- Alzheimer’s disease: Current Opinion in Clinical Nutrition ological and pathological brain function. Trends in Neu- and Metabolic Care, 16(4), 440–445. https://doi.org​/10​ rosciences, 36(10), 587–597. https://doi.org/10.1016/j.tins​ .1097​/MCO.0b013e328361c7d1 .2013​.07.001 [5] Nutrition, C. for F.S. and A. (n.d.). Food Additives & Ingre- [15] Alten, B., Yesiltepe, M., Bayraktar, E., Tas, S.T., Goc- dients—High Fructose Corn Syrup Questions and An- men, A.Y., Kursungoz, C., Sara, Y. (2018). High fruc- swers [WebContent]. Retrieved September 27, 2018, from tose corn syrup consumption in adolescent rats causes https://www.fda.gov/food/ingredientspackaginglabeling​ ­bipolar-like behavio-ral phenotype with hyperexcitability /­foodadditivesingredients/ucm324856.htm in hippo-campal­ CA3-CA1 synapses. British Journal of [6] DiNicolantonio, J.J., O’Keefe, J.H., & Lucan, S.C. (2015). Add- Pharmacology. https://doi.org/10.1111/bph.14500 ed Fructose: A Principal Driver of Type 2 Diabetes Mellitus [16] Westwater, M.L., Fletcher, P.C., & Ziauddeen, H. (2016). and Its Consequences. Mayo Clinic Proceedings, 90(3), 372– Sugar addiction: the state of the science. European Journal 381. https://doi.org/10.1016/j.mayocp​.2014​.12.019 of Nutrition, 55(2), 55–69. https://doi.org/10.1007/s00394​ [7] Freeman, C.R., Zehra, A., Ramirez, V., Wiers, C.E., Volkow, -016​-1229-6 N.D., & Wang, G.-J. (2018). Impact of sugar on the body, [17] Hoebel, B.G., Avena, N.M., Bocarsly, M.E., & Rada, P. brain, and behavior. Frontiers in Bioscience (Landmark Edi- (2009). A Behavioral and Circuit Model Based on Sug- tion), 23, 2255–2266. ar Addiction in Rats. Journal of Addiction Medicine, 3(1), [8] Clapp, M., Aurora, N., Herrera, L., Bhatia, M., Wilen, E., 33–41. https://doi.org/10.1097/ADM.0b013e31819aa621 & Wakefield, S. (2017). Gut microbiota’s effect on men- [18] World Health Organization: Sugar intake for adults and tal health: The gut-brain axis. Clinics and Practice, 7(4). children. (2015). Retrieved October 7, 2018, from http:// https://doi.org/10.4081/cp.2017.987 www​.who.int/nutrition/publications/guidelines/sugars​ [9] Natividad, J.M., Huang, X., Slack, E., Jury, J., Sanz, Y., Da- _intake/en/ vid, C., . . . Verdú, E.F. (2009). Host Responses to Intesti- [19] Walker, R.W., Dumke, K.A., & Goran, M.I. (2014). Fruc- nal Microbial Antigens in Gluten-Sensitive Mice. PLOS tose content in popular beverages made with and with- ONE, 4(7), e6472. https://doi.org/10.1371/journal.pone​ out high-fructose corn syrup. Nutrition, 30(7), 928–935. .0006472 https://doi.org/10.1016/j.nut.2014.04.003 [10] Doig, C.J., Sutherland, L.R., Dean Sandham, J., Fick, G.H., [20] “Added Sugars.” www.heart.org. Accessed April 29, 2019. Verhoef, M., & Meddings, J.B. (1998). Increased Intesti- https://www.heart.org/en/healthy-living/healthy-eating​ nal Permeability Is Associated with the Development of /­eat-smart/sugar/added-sugars Multiple Organ Dysfunction Syndrome in Critically Ill [21] Kendig, M.D. (2014). Cognitive and behavioral effects of ICU Patients. American Journal of Respiratory and Criti- sugar consumption in rodents. A review. Appetite, 80, 41– cal Care Medicine, 158(2), 444–451. https://doi.org/10.1164​ 54. https://doi.org/10.1016/j.appet.2014.04.028 /­ajrccm​.158.2.9710092 [22] Goran, M.I., Ulijaszek, S.J., & Ventura, E.E. (2013). High [11] Odenwald, M.A., & Turner, J.R. (2013). Intestinal permea- fructose corn syrup and diabetes prevalence: A global per- bility defects: is it time to treat? Clinical Gastroenterology spective. Global Public Health, 8(1), 55–64. https://doi.org​ and Hepatology: The Official Clinical Practice Journal of the /10​.1080/17441692.2012.736257

Manoa Horizons 4 Online.indb 89 9/9/2019 11:23:26 PM