I have a sweet tooth: will it bite and kill me?
Unfortunately yes, and more on why virtue is difficult and often suboptimal
Under the Mailard reaction, glycation occurs: proteins become irreversibly bonded with sugar. In our bodies, advanced glycation end products (AGEs) are a function of this process being triggered at room temperature, with sugar forming covalent bonds with proteins, lipids, and nucleic acids, and are thought to be one of the main drivers of ageing. Indeed, the glycation of haemoglobin is a core symptom of type II diabetes [1]. Their receptors (RAGEs) also contribute to ageing via triggering inflammation and oxidative stress; amongst other mechanisms, they bind to ligands, which is not only pro-inflammatory but also contributes to mitochondrial dysfunction and senescence. Their accumulation in our bones and muscles is a large part of why the elderly are so frail. Their levels are correlated with increased risk of chronic age-related diseases, including cardiovascular and neurodegenerative diseases.
Of course, you may be wondering whether this is merely correlation, and if AGE accumulation is instead a symptom of ageing? Here is a useful DAG produced by ChatGPT, yet theory does suggest a causal link. They are known to damage our metabolism as well as being a symptom of compromised metabolism, for instance via impairing our insulin response, so a causal factor implicated in type II diabetes too.
AGEs can form endogenously (via the inherent decline in metabolism with age), and exogenous sources can increase their accumulation. Those sources include diet, smoking [2], and air pollution. Here I will focus primarily on diet.
In general, animal-based products have the highest levels of dietary AGEs whilst whole-food plant based diets yield the lowest levels [3]. Excess carbohydrate intake and sedentary lifestyles are also bad in this respect, for obvious reasons. Shorter cooking times, lower temperatures, and acidic liquids reduce AGEs from our diet. However, one limitation is that these databases tend to use a single dietary AGE, carboxymethyl-lysine (CML), as a proxy for total dietary AGE concentration, and the different methods of measuring this don't always agree, albeit they do correlate. Moreover, one proxy oversimplifies the rather broad mechanisms via which dAGEs can form - dependent on the reactivity of carbonyl with the free amino acids, as well as the environmental pH and temperatures in cooking or preparation. Likewise, nonenzymatic glycation can occur via sugar derivatives too, such as acetaldehyde [4]. There is also heterogeneity in the metabolic effects of dAGEs, with animal-based dAGEs being substantially worse than plant-derived.
Now I think the problem has become apparent - nearly all of the most pleasurable foods and drinks in life increase exogenous AGE levels. Indeed, if I was to suggest a grand unified theory of ageing, it would be that immediate pleasure is the primary reason today why we age. I have a sweet tooth, yet I also like meat, and socialising (which always involves either sugary soft, non-alcoholic, or alcoholic drinks). On the margin, I will shift more towards a whole-food plant based diet, although this is largely my diet anyhow. I don't smoke tobacco, and exercise is a ubiquitous feature of my life, so I'm advantaged in this respect. Of course, you can make a substantial difference via using slower cooking methods at lower temperatures, adding vinegars, or actually squeezing your lemon when served with it at a restaurant. Although alcohol yields substantial externalities and health costs (which I will delineate in further posts), I won't go teetotal (for reasons I'll explain in a future post), although I do recommend sticking to UK government guidelines.
Nonetheless, you can substantially undercut your dAGE intake via eating plenty of fruits. I think, for every portion of meat, or sugary carbohydrate, or drink I have, I will match it one for one with an equivalent intake of fruit. Besides paying closer attention to cooking practices, this is the only way one can mitigate the inherent immediate pleasure vs longevity tradeoff here.
HbA1c measures a rolling average of this glycation over the last 100 days or so.
Another reason why marijuana is bad for your physical health.
Fructose actually substantially reduces HbA1c levels immediately and in the hours after consumption, so fruit is beneficial in this respect. These results are indeed supported by the gold standard in empirical science. This, as well as the inherently high levels of saturated fat intake, is one reason why keto diets are a scam. Keto diets also increase levels of methylglyoxal, another sugar derivative known to glycate.
Non-alcoholic beers or wines are also incredibly high in sugar levels (as I discovered via ordering the non-alcoholic cider at a pub), as are soft drinks, so teetotalism won't necessarily save you here. In general, I feel that teetotalers fail to account for opportunity cost, and demonstrate that the alternatives are necessarily healthier. Admittedly diet coke is an exception, with aspartame not demonstrating a clear risk to health or longevity (as detailed in previous posts), yet I dislike the bitterness of such (without the compensatory roasty or smoky taste of black coffee), and I want more variety in my drinks than diet sodas.