How Fructose Affects the Brain and Why Fruit Shouldn’t Get a Pass When it comes to Sugar

One of the biggest misunderstandings in the field of nutrition is the role of fruit in a healthy diet.  We have been told to eat more fruits and vegetables for so long, that the two are referred to almost synonymously.  There is definitely a problem with this association.  Vegetables are rich in fiber, minerals, and typically very low in sugar.  Fruit, on the other hand, is typically much lower in micronutrients and fiber, yet much higher in sugar.  The most notable sugar in fruit is fructose.

While many people are justifiably concerned with the amount of sugar in soft drinks and the role that high fructose corn syrup is playing in the development of chronic disease, very few consider the role of fruit juice and high fruit consumption to this problem.  Sure, it is always better to eat fruit, even the sweetest types, than to eat refined, processed sweeteners.  There will be at least modest upsides to these better choices.   Bananas offer some vitamin B6 and decent levels of potassium, grapes contain antioxidants in their skins if they are darker varieties, and mangos contain the carotenoid alpha carotene, a precursor to vitamin A- yet each of these are all particularly rich sources of naturally occurring fructose.

Most adults can safely tolerate fructose at levels below 25 grams per day, or approximately 10 grams per meal.  These are numbers that have been generated by looking at various aspects of fructose metabolism and their associated biomarkers.   These biomarkers range from uric acid (generated by fructose) to lipopolysaccharides (molecules produced by gut microbes fed fructose-rich meals). They can be found in the blood, breath, and gut. High levels of fructose can feed the wrong microbes and create gut issues.  These events can be detected by measuring breath hydrogen content in subjects after consuming varying levels of fructose.  Higher levels of hydrogen reflect an increasing trend towards dysbiosis, small intestinal bacterial overgrowth, and malabsorption.  The liver also struggles to metabolize high levels of fructose safely.  These challenges are measured through the triglyceride levels of an individual after ingesting a fructose-rich meal.  Fructose also affects the brain, often in profound ways.

It is well understood how fructose contributes to obesity, insulin resistance, and other components of metabolic syndrome (1).  Equally accepted is the relationship between dietary fructose and NAFLD (non alcoholic fatty liver disease) (2).  Researchers have recently shown that fructose influences gene expression and DNA repair processes (3). The underlying mechanism with this and other processes that connect chronic fructose consumption to disease is simple.  Fructose metabolism requires the addition of phosphorus before it can be utilized for energy.  This is very different than glucose metabolism that requires no alterations before it can be converted to energy.  Phosphorus is usually taken from ATP molecules.  The process causes disruptions in the mitochondria and increased free radical damage, higher levels of oxidative stress, and ultimately a loss of mitochondrial function.  Thus, although fructose is natural and is tolerated in low to modest amounts, it can easily damage various aspects of human physiology and can be seen as a plant-based toxin.

In 2009, an investigation showed how higher levels of dietary fructose that caused memory loss in animals (4).  The researchers involved theorized that this was at least in part due to the formation of advanced glycosylated proteins, often referred to as AGEs.  The crosslinks formed between proteins in our body and circulating fructose, usually rendered the protein useless in the end.  Now, a more recent study suggests that the memory loss may be more reflective of overall brain damage.  This damage is largely inflammatory-based (5).  Rats with traumatic brain injury were subjected to varying levels of dietary fructose and their recovery process was followed for several weeks.  Those rats with even modest dietary fructose levels had impaired recovery and an overall decrease in brain plasticity, something that is essential for regaining cognitive function.  The authors conclude, “These data suggest that fructose consumption reduces neural resilience and may predispose the brain toward cognitive dysfunction and lifelong susceptibility to neurological disorders.”

There is a relatively low ceiling for fructose in our diet or enteral formula, whether from added sugar, fruit juice, or too much fruit.

~ John Bagnulo MPH, PhD.

RESOURCES:

1. DiNicolantonio JJ, Berger A. Added sugars drive nutrient and energy deficit in obesity: a new paradigm. Open Heart. 2016;3(2):e000469. doi:10.1136/openhrt-2016-000469.

2. Mota M, Banini BA, Cazanave SC, Sanyal AJ. Molecular Mechanisms of Lipotoxicity and Glucotoxicity in Nonalcoholic Fatty Liver Disease. Metabolism: clinical and experimental. 2016;65(8):1049-1061. doi:10.1016/j.metabol.2016.02.014.

3. Cioffi F, Senese R, Lasala P, et al. Fructose-Rich Diet Affects Mitochondrial DNA Damage and Repair in Rats. Nutrients. 2017;9(4):323. doi:10.3390/nu9040323.

4. Ross AP, Bartness TJ, Mielke JG, Parent MB. A High Fructose Diet Impairs Spatial Memory in Male Rats. Neurobiology of learning and memory. 2009;92(3):410-416. doi:10.1016/j.nlm.2009.05.007.

5. Agrawal R, Noble E, Vergnes L, Ying Z, Reue K, Gomez-Pinilla F. Dietary fructose aggravates the pathobiology of traumatic brain injury by influencing energy homeostasis and plasticity. Journal of Cerebral Blood Flow & Metabolism. 2016;36(5):941-953. doi:10.1177/0271678X15606719.