New Theory in dementia research: could fructose trigger Alzheimer’s?

Fruit sugar – from the name alone, you might think it’s healthy. The fact that fruit sugar, also known as “fructose” in technical jargon, hardly raises blood sugar levels due to its low glycemic index and is largely metabolized independently of insulin, also led to the assumption in the past that it would have a favourable effect on health. For this reason, it used to be recommended to patients with diabetes mellitus as a safe sugar alternative.   

In the meantime, new studies have deepened our understanding of fructose, and we know that its effects on human metabolism are not as beneficial as we thought. Nevertheless, to this day it still has the best image imaginable: it is promoted in public as “harmless sugar” or even “healthy sugar” and is used excessively as an industrial sweetener, e.g. in the form of enzymatically processed corn syrup, due to lower production costs and higher sweetening power compared to household sugar (sucrose). We may also consume quite high amounts of fructose via supposedly healthy sources (e.g. fruit juice, acacia syrup).

But can we do this without hesitation? The answer is clearly NO! 

What makes fructose so dangerous? 

Experts have known for quite some time that fructose can have an unfavourable effect on health. The reason for this is that – in contrast to glucose metabolism – the entire burden of metabolizing fructose lies with the liver. Fructose is very quickly converted into fat and stored under strong energy consumption. It is therefore not surprising that numerous study results in recent years have shown that the preferential use of this type of sugar can increase obesity, fatty liver, poor LDL cholesterol levels, elevated uric acid levels with resulting gout disease and high blood pressure develop. It is also known that regular consumption of large amounts of fructose over a prolonged period can lead to insulin resistance by decreasing the sensitivity of cells to insulin. Overall, excessive use of fructose is a key factor in the increasing prevalence of metabolic diseases, such as non-alcoholic fatty liver, and another element in promoting underlying chronic inflammation in the body (1). 

But it gets worse: more and more studies report a close link between fructose and Alzheimer’s disease, and it is now known with great certainty that too much fructose is extremely harmful to our brains. In addition to numerous studies in animal models, this is confirmed by a number of human studies suggesting a link between fructose consumption and cognitive dysfunction: for example, the Framingham Heart Study showed that consumption of soft drinks and fruit juices containing high levels of fructose correlated quite clearly with a dose-dependent volume reduction in total brain, especially the hippocampal volume, correlating with a deterioration in episodic memory (2). The brains of young children are particularly vulnerable to the deleterious effects of fructose (3). 

Fructose metabolism was a survival program in prehistoric times 

In a recent study published in March 2023 (4), scientists at the University of Colorado found a surprising link between prehistoric foraging and Alzheimer’s disease: fructose. 

This is because, unlike today, resources essential for survival, such as sufficient food, water and oxygen, were not assured in those days. As soon as these became scarce, the human organism helped itself with a kind of survival program, the production of fructose. This sugar can specifically influence brain areas, so that humans were able to focus and thus effectively catch prey. This required rapid reaction, a high degree of impulsivity and exploratory behavior with a willingness to take risks, while traits such as thinking too long, disturbing thoughts, memories, emotions and a sense of time were more of a hindrance. 

Fructose achieves precisely these effects in the brain by decreasing blood flow in the cerebral cortex and other important areas (such as the hippocampus, cingulate cortex, and thalamus) while increasing blood flow in the visual cortex area associated with food reward (5). 

Is Alzheimer’s disease an adaptation to an evolutionary survival pathway? 

Thus, the authors of this study (4) suggest that the fructose-dependent reduction of metabolism in these brain regions was initially reversible and thought to be beneficial from an evolutionary point of view. In other words, fructose metabolism was a vital process in the primitive period, which was characterized by resource scarcity, to use the small energy pool sensibly and to survive. 

Today, on the other hand, we live in a time when there is a great abundance of resources, at least in the Western world. Fructose is consumed excessively, especially through industrially sweetened foods, beverages and lifestyle products. However, the fructose metabolism does not recognize any difference: the “survival mechanism” remains switched on when fructose consumption is high, and even worse: this in turn leads to excessive consumption of foods high in fat, sugar and salt, which triggers additional fructose production in the body. A vicious circle begins. 

It has already been demonstrated by imaging diagnostics that in Alzheimer’s disease, a decline in glucose metabolism and intracellular ATP levels sets in early in certain brain areas, such as the hippocampus, entorhinal cortex, posterior cingulate cortex, and middle temporal gyrus, with other areas being spared in contrast (6). This corresponds quite closely to the regions that are also affected by fructose. 

The scientists from Colorado therefore suspect that the fructose metabolism that is constantly switched on by today’s lifestyle, resulting in energetic cellular undersupply, mitochondrial dysfunction and the associated oxidative stress, can therefore lead to neuronal inflammation (neuroinflammation) and cerebral insulin resistance. This would be extremely fatal for Alzheimer’s sensitive brain areas, such as the hippocampus, and could lead to progressive neuronal (nerve cell) death and brain atrophy (shrinkage of brain mass) with all the hallmarks of Alzheimer’s disease. 

The authors conclude that Alzheimer’s disease may be a deleterious adaptation to this evolutionary fructose-mediated survival pathway. 

Although this is only a hypothesis, scientists agree on the detrimental effect fructose has on cognitive function, especially when consumed in the form of liquid sugar and/or simply too much of it. 

The good news, however, is that with this knowledge, you could avoid fructose overload in your diet. Here are our recommendations: 

• Avoid industrially produced foods, as they are usually “over-sweetened”, i.e. contain far too much sugar, and the highly fructose-containing liquid sugar is usually used for this purpose. 

• Read carefully in the ingredients list, because fructose likes to hide under other names such as “fructose” “fructose syrup”, “fructose-glucose syrup”, “glucose-fructose syrup”, “fruit sweetener”, “corn syrup” or “isoglucose”. 

• Also at home, avoid the use of household sugar, which is also 50% fructose. 

• If possible, do not drink undiluted fruit juices or concentrated fruit spritzers, as these contain high amounts of fructose that are quickly absorbed. 

• In contrast, you can consume fruit, at least in normal quantities / in moderation, without hesitation, preferably in organic quality and with peel. The naturally occurring fructose contained in fruit is largely uncritical, provided that there are no pre-existing health problems. 

• Also avoid the alternative sweetener from agave syrup, which is often propagated as part of a healthy diet: it contains significantly higher amounts of fructose than household sugar. 

• Try not to exceed a fructose amount of 25 g per day. 

• In addition, to avoid starting the body’s own fructose production as much as possible, avoid drinking alcohol, eating empty carbohydrates (such as white bread), and eating heavily salted foods. 

Feel free to visit us at Knowledge stops Dementia – here you will find even more in-depth information on the topic of sugar and many other interesting options for effective Alzheimer’s prevention.  

Start today – your (brain) health will thank you! 

References: 

1. Basaranoglu, Metin; Basaranoglu, Gokcen; Sabuncu, Tevfik; Sentürk, Hakan (2013): Fructose as a key player in the development of fatty liver disease. In: World J. Gastroenterol. 19 (8), S. 1166–1172. DOI: 10.3748/wjg.v19.i8.1166.  
2. Pase, M. P., Himali, J. J., Jacques, P. F., DeCarli, C., Satizabal, C. L., Aparicio, H., et al. (2017). Sugary beverage intake and preclinical Alzheimer’s disease in the community. Alzheimers Dement. 13, 955–964. doi: 10.1016/j.jalz.2017.01.024  
3. Cohen, J. F. W., Rifas-Shiman, S. L., Young, J., and Oken, E. (2018). Associations of prenatal and child sugar intake with child cognition. Am. J. Prev. Med. 54, 727–735. doi: 10.1016/j.amepre.2018.02.020  
4. Richard J. Johnson, Dean R. Tolan, Dale Bredesen, Maria Nagel, Laura G. Sánchez-Lozada, Mehdi Fini, Scott Burtis, Miguel A. Lanaspa, David Perlmutter, Could Alzheimer’s disease be a maladaptation of an evolutionary survival pathway mediated by intracerebral fructose and uric acid metabolism?, The American Journal of Clinical Nutrition, 2023, ISSN 0002-9165, https://doi.org/10.1016/j.ajcnut.2023.01.002. 
5. Page KA, Chan O, Arora J, Belfort-Deaguiar R, Dzuira J, Roehmholdt B, Cline GW, Naik S, Sinha R, Constable RT, et al. Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways. JAMA 2013;309(1):63-70.doi:10.1001/jama.2012.116975.  
6. Brun A, Gustafson L. Distribution of cerebral degeneration in Alzheimer’s disease. A clinico- Journal Pre-proof pathological study. Arch Psychiatr Nervenkr (1970) 1976;223(1):15-33. doi: 10.1007/BF00367450  

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