Sugar and Metabolic Insult 

Previously in part 1 of our series, Gillian discussed how sugar and HFCS won’t to kill you, in a specific context. But in what context is sugar and HFCS actually toxic? In this part of the series, we will take a deep dive into the metabolic impact of the sugar and HFCS. 

Define Toxic. 

Before we get into the nitty-gritty, let’s go ahead and define the context of toxic. First things first, let’s clarify our semantics. Many people make definitive statements without full understanding.

According to Harrison’s Principles of Internal Medicine:

Toxicity: The degree to which a substance and harm humans or animals

 Acute Toxicity: involves harmful effects in an organism through a single or short-term exposure. 

Subchronic Toxicity: The ability of a toxic substance or mixture of substances to cause effects for more than 1 year but less than an entire lifetime of the organism. 

Chronic Toxicity: The ability of a substance or mixture of substances to cause harmful effects over an extended period, usually upon repeated or continuous exposure, sometimes lasting the entire life of the organism.

As you can see, the word toxic can be subdivided into the 3 aforementioned categories based on how long/often a substance is exposed and how long it takes to cause insult. Therefore, it is important that we make this clear: Acute toxicity is NOT the same as chronic toxicity.  

 It is also important to consider that there is a statistical distribution of toxicity of substances to subject. Let’s take alcohol for example. Some people may have 2 drinks before they begin to feel drunk, and others may not be phased by 5. In short, there is a spectrum of susceptibility to any toxin. 

What we want to shed light on here is how we get to chronic toxicity, right? When we have too much sugar too often, what happens? 

Well going back to our alcohol example, it is important to remember that what we do eat, and drink is cumulative. Even taking in alcohol in smaller doses repeatedly speeds up the aging process, disrupts neural pathways, leads to cardiomyopathy (stretching and dropping of the heart muscle), arrhythmias, high blood pressure, fatty liver disease, pancreatitis, cancer, aaaand you get my point… Which is this: just because a dose doesn’t result in acute toxicity immediately doesn’t mean that it can’t or won’t result in chronic toxicity. 

High Fructose Corn Syrup

It has been both researched and argued that sugar is a unique macromolecule, distinct from other carbohydrates. Studies have shown that sugar is not “just” an empty calorie. Many arguments have been made that the toxicity of sugar is related to itshepatic (liver) metabolism. Specifically, in excess (another context word), fructose increases VLDL production (very low-density lipoprotein), which carry triglycerides (a type of fat) to your tissues. Which in turn increases apoB (an important component of many lipoproteins that are involved in atherosclerosis and cardiovascular disease) or LDL-P due to carrying more triglycerides. Mechanistic studies suggest that cardiovascular disease and metabolic syndrome result from the rapid hepatic metabolism of fructose catalyzed by a specific enzyme that generates a precursor for de novo lipogenesis (making of new fat) and leads to increased uric acid levels (which can lead to gout). Research also shows that at reasonable doses, insulin resistance is worsened which amplifies the harm that other foods may have on your body. 

Like many topics in the fitness industry, there are debates on ideas in the world of scientific research. But even those who don’t subscribe to the camp of sugar being metabolically significant, some argue that fructose consumptions may impact subsequent food consumption in a way that plain glucose doesn’t. We can probably stand by this from an anecdotal standpoint as well. When we eat sugar, we may not feel satiated or may crave even more food, which serves as a decent Segway into my next point: that there is emerging research to show that sugar is addictive. Even in ways comparable to heroin or cocaine as suggested by MRI. So even if you don’t buy that sugar is harmful, it may make you eat more which we saw from Gillian’s article can be the harm in itself. 

If your and APOE4 allele carrier like me (a gene that increases your risk for Alzheimer’s and dementia), then controlling sugar consumption is imperative in this respect. This will have to be an article for another day, but long story short: someone who is predisposed to Alzheimer’s, dementia, or any other early onset of cognitive decline has to spare the glucose metabolism of their brain in order to try and conserve optimal cognition. Eating too much sugar may speed up the onset of cognitive decline if you are not careful (let us know if you’d like an article that dives deep into the neurological effect of food!)

Thank you for reading!

Laid out for you are a few different points as to how sugar can be harmful, but what we haven’t really gotten into is dose, and at the end of the day it’s the dose that kills you not the drug. Therefore asking “is sugar toxic” becomes a dumb question. It’s the same thing as me asking “is water toxic?” or “is oxygen toxic?”. YES, water and oxygen can be lethal at extremely high doses. I mean, still appreciate that they are essential to life, but know that too much of anything is bad for you.

Circling back to Laurin’s intro, context is key. Luckily, there are amazing researchers that have considered host factors, genetic predispositions, etc. and that sometime in the near future we can have a definitive answer on what does hurts who. Tune in TOMORROW for Part 3, where we discuss the “happy medium” and practical applications for you! 


Stanhope, K. L., Schwarz, J. M., & Havel, P. J. (2013). Adverse metabolic effects of dietary fructose: results from recent epidemiological, clinical, and mechanistic studies. Current Opinion in Lipidology, 24(3), 198.

 Zimmerman, H. J. (1999). Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. Lippincott Williams & Wilkins.

 Stanhope, K. L. (2012). Role of fructose-containing sugars in the epidemics of obesity and metabolic syndrome. Annual review of medicine, 63, 329-343.

 Stanhope, K. L., Bremer, A. A., Medici, V., Nakajima, K., Ito, Y., Nakano, T., … & Keim, N. L. (2011). Consumption of fructose and high fructose corn syrup increase postprandial triglycerides, LDL-cholesterol, and apolipoprotein-B in young men and women. The Journal of Clinical Endocrinology & Metabolism, 96(10), E1596-E1605.

Attia, Peter. “Is Sugar Toxic?” The Nerd Safari, 2013 blog, Link to post (

 HFCS Image: By Jü – Own work, CC0,