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Fructose: The influences on our brain and body

EnFuse Institute For Learning

Category: Health & Wellness


Fructose, commonly known as fruit sugar, is so named because of its concentrated presence in fruits.1 It is also found in honey as well as in some vegetables. Fructose is a simple sugar that combines with glucose to form sucrose, also known as cane sugar or table sugar. Fructose is an important sugar in terms of its utility as an energy source and is similar in structure to glucose. One key difference however, is that fructose per gram is twice as sweet as glucose and for this reason fructose is commonly used as a sweetening agent in processed foods.2 Fructose in the form of high-fructose corn syrup (HFCS) was introduced commercially in the 1970s and while the consumption of HFCS since then has decreased, the consumption of fructose from sucrose has increased.2
In light of growing global obesity levels and associated health concerns, fructose, HFCS and sucrose have been extensively studied as potential contributing factors to this epidemic. Since the commercialization of fructose, its increased consumption has coincided with increased levels of obesity3 and while there is still not consensus on the nature of the association, the deleterious health effects of a long-term high fructose diet are well understood.

Advanced Glycation End Products (AGEs)

Glycation is a process in which sugars or sugar polymers attach to proteins or lipids in a nonenzymatic reaction known as the Millard reaction, named for the early twentieth century chemist who discovered it.4 This means that sugar inside or outside the cell can spontaneously react with lipids and proteins changing them into new compounds. The higher the blood sugar level and the longer the sugar remains in the blood, the greater the extent of the glycation.4 Once a Millard reaction has occurred, these new compounds can undergo further reactions and rearrangements to form advanced glycation end products (AGEs). These drastically change the properties of the affected proteins and therefore wreak havoc on cells. The fact that fructose is 8-10 times more reactive than glucose in Millard reactions means that a high blood fructose concentration results in more harmful effects in a shorter period of time.5 Over longer periods, AGEs promote the release of pro-inflammatory molecules such as cytokines that contribute to degenerative diseases.6

Fructose and the Body

The digestion, absorption and metabolism of fructose compared to glucose differ in key ways that contribute to increased energy consumption related to obesity and associated health issues including cardiovascular disease. The glycation of proteins such as collagen and elastin affect the integrity of vascular and connective tissues. The combined effects of cytokines can lead to damage of arterial blood vessels causing atherosclerosis – a serious vascular disease.5

One frightening emerging trend is that consumption of HFCS sweetened drinks or drinks high in free fructose is now associated with arthritis in young adults aged 20-30 years.7 This is primarily due to the fact that the AGEs that form in the gastrointestinal tract of individuals consuming large amounts of these drinks are subsequently absorbed and travel to other regions of the body where they undergo further reactions and promote more inflammation. Collagen is an abundant protein throughout the body and is the major component of connective tissue in bones and joints. Previously, inflammatory diseases such as arthritis were only seen in older individuals resulting from the normal wear and tear that occurs in joints over time. Now, due to the inflammation-promoting effects of AGEs, this type of disease has emerged in a younger demographic.

The consumption of excess fructose not only promotes inflammation throughout the body but it can damage specific organs as well. Fructose metabolism occurs in the liver. Not surprisingly, this organ more than any other is most affected by excess consumption of fructose. The properties of fructose metabolism cause the process to be very lipogenic – fat producing. This causes two major problems: excess cholesterol and triglycerides in the blood (dyslipidemia) and non-alcoholic fatty liver disease. The former contributes to metabolic syndrome and the latter causes elevated liver enzymes that can cause complete shutdown of the organ.8

In fact, the lipogenic effects of a high fructose diet on the liver are greater than that of a high fat diet. Additionally, fructose metabolism further contributes to fatty liver disease by promoting insulin resistance since fructose, unlike glucose, does not require insulin to be metabolized.8
The pancreas is yet another organ that is affected by a high fructose diet. The AGEs produced from excess fructose in the blood can irreversibly damage pancreatic ß-cells leading to a reduction in insulin secretion.6 The death of these cells damages the pancreas and invariably lead to diabetes mellitus.

Fructose and the Brain

In humans, feeding behavior is a complex mechanism that relies on the interplay of hormonal and neural signals from the gastrointestinal tract and adipose tissue along with external stimuli from the environment (sight, smell, taste etc.) all integrated by the brain and used to regulate appetite and metabolic processes.9 The hormones leptin, insulin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY) and cholecystokinin (CCK) play a role in promoting feelings of satiety while the hormone ghrelin produced by cells in the stomach and small intestine triggers feelings of hunger. Leptin is produced by adipose tissue in proportion to their mass and is regulated by insulin.9


A high fructose diet promotes weight gain because, unlike glucose, it does not suppress the release of ghrelin and only promotes the release of small amounts of insulin, GLP-1 and leptin into the blood.9 Fructose ingestion also does not blunt the brain’s response to visual food cues and in fact activates regions of the brain associated with attention and reward and so prolongs food seeking behavior.10 Furthermore, the region of the brain that integrates signals related to feeding behavior, the hypothalamus, rapidly depletes its energy stores when it metabolizes fructose rather than glucose which subsequently promotes overeating.10

A high fructose diet can have even more deleterious effects in an individual that is insulin resistant or insulin insensitive. This is because in someone who is insulin resistant there is a diminished suppression of ghrelin by both glucose and fructose compared to someone who is not insulin resistant who would have diminished response to only fructose.11

Healthy Alternatives to Industrialized Fructose

Several strategies exist for combatting and avoiding the effects of a high fructose diet and they by and large involve regulating intake and making common sense substitutions. Fructose, like any other simple sugar is not unhealthy but can be harmful when not consumed in moderation. The consumption of normal levels of fructose where no more than 18% of calories come from concentrated fructose sources such as HFCS or sucrose and no more than 9% of calories come from regular fructose sources has been shown to not promote aspects of metabolic syndrome or increase risk of cardiovascular disease.12

Sugary beverages are one of the most common sources of HFCS and sucrose. Replacing a single serving of sugar sweetened beverage with water has been shown to reduce weight gain by 0.49 kg over a 4-year period13 and significantly lowers the risk of diabetes. While 100% fruit juice is often considered an alternative to sugar sweetened beverages especially for their vitamin content, they still represent a significant source of natural sugars. It is recommended that only 4-6 oz of 100% fruit juice be consumed per day.13

Similarly, simply switching from processed food to organic or whole food alone does not promote healthy living. The amount of food consumed also needs to be commensurate with energy needs.14 A balanced diet and adequate exercise are both needed to promote overall health. To that effect, suppliers of these high energy processed foods, namely fast food restaurants, would greatly impact the obesity epidemic if they reduced the amount of sugar and fat added to their food and drinks.14 This combined with lifestyle changes would certainly produce a healthier populace.


1. Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002. Section 11.1, Monosaccharides Are Aldehydes or Ketones with Multiple Hydroxyl Groups. Available from: https://www.ncbi.nlm.nih.gov/books/NBK22547/

2. Rippe JM, Angelopoulos TJ. Sucrose, High-Fructose Corn Syrup, and Fructose, Their Metabolism and Potential Health Effects: What Do We Really Know? Advances in Nutrition. 2013;4(2):236-245. doi:10.3945/an.112.002824.

3. Rippe JM. The Health Implications of Sucrose, High-Fructose Corn Syrup, and Fructose: What Do We Really Know? Journal of Diabetes Science and Technology. 2010;4(4):1008-1011.

4. Rabbani N, Ashour A, Thornalley PJ. Mass spectrometric determination of early and advanced glycation in biology. Glycoconjugate Journal. 2016;33:553-568. doi:10.1007/s10719-016-9709-8.

5. Gugliucci A. Formation of Fructose-Mediated Advanced Glycation End Products and Their Roles in Metabolic and Inflammatory Diseases. Advances in Nutrition. 2017;8(1):54-62. doi:10.3945/an.116.013912.

6. You J, Wang Z, Xu S, et al. Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic ß-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation. Journal of Diabetes Research. 2016;2016:9073037. doi:10.1155/2016/9073037.

7. DeChristopher LR, Uribarri J, Tucker KL. Intake of high-fructose corn syrup sweetened soft drinks, fruit drinks and apple juice is associated with prevalent arthritis in US adults, aged 20–30 years. Nutrition & Diabetes. 2016;6(3):e199-. doi:10.1038/nutd.2016.7.

8. Softic S, Cohen DE, Kahn CR. Role of Dietary Fructose and Hepatic de novo Lipogenesis in Fatty Liver Disease. Digestive diseases and sciences. 2016;61(5):1282-1293. doi:10.1007/s10620-016-4054-0.

9. Page KA, Chan O, Arora J, et al. Effects of Fructose vs Glucose on Regional Cerebral Blood Flow in Brain Regions Involved With Appetite and Reward Pathways. JAMA?: the journal of the American Medical Association. 2013;309(1):63-70. doi:10.1001/jama.2012.116975.

10. Luo S, Monterosso JR, Sarpelleh K, Page KA. Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards. Proceedings of the National Academy of Sciences of the United States of America. 2015;112(20):6509-6514. doi:10.1073/pnas.1503358112.
11. Van Name M, Giannini C, Santoro N, et al. Blunted Suppression of Acyl-Ghrelin in Response to Fructose Ingestion in Obese Adolescents: the Role of Insulin Resistance. Obesity (Silver Spring, Md). 2015;23(3):653-661. doi:10.1002/oby.21019.

12. Angelopoulos TJ, Lowndes J, Sinnett S, Rippe JM. Fructose Containing Sugars at Normal Levels of Consumption Do Not Effect Adversely Components of the Metabolic Syndrome and Risk Factors for Cardiovascular Disease. Nutrients. 2016;8(4):179. doi:10.3390/nu8040179.

13. Malik VS, Hu FB. Fructose and Cardiometabolic Health: What the Evidence from Sugar-Sweetened Beverages Tells Us. Journal of the American College of Cardiology. 2015;66(14):1615-1624. doi:10.1016/j.jacc.2015.08.025.

14. Van Buul VJ, Tappy L, Brouns FJPH. Misconceptions about fructose-containing sugars and their role in the obesity epidemic. Nutrition Research Reviews. 2014;27(1):119-130. doi:10.1017/S0954422414000067.


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