ESPE Yearbook of Paediatric Endocrinology

Cell 2018;175:605–614.
DOI: 10.1016/j.cell.2018.07.044.
http://www.ncbi.nlm.nih.gov/pubmed/30340032

Summary: Epidemiological, clinical intervention trials and experimental evidence indicate the negative impact of excessive carbohydrate uptake. This review details the history of carbohydrate consumption and mechanisms of carbotoxicity, as well as the beneficial effects of reducing carbohydrates in the diet.

Comment: After we adopted the idea of lipotoxicity and glucotoxicity, a new term is coined, “carbotoxicity”. It refers to toxicity secondary to the excessive intake of different types of carbohydrates: glucose, fructose and mannose.

The history of dietary carbohydrates includes three major, transformative steps. The first was the transition from hunter-gatherers to agriculture, which shifted carbohydrate intake from fruits, seeds, nuts and roots, to a range of cereals (in Europe), rice (in Asia), corn (in Mesoamerica) and potatoes (in South America). After this transition, carbohydrate intake was estimated as contributing 15–30% of total energy intake. The second major change in carbohydrate intake occurred in the 19th and 20th centuries, and is marked by the mass production and consumption of refined sugars, which changed the eating habits of Europeans as they started consuming jams, candy and processed foods. The third and most significant surge in carbohydrate intake was after World War II, and is linked to the rising ingestion of ultra-processed food items, sodas and high-fructose corn syrup; consequently, carbohydrate intake reached 45%–65% of total energy intake.

In contrast to beliefs that have been held for decades, the authors state that digestible carbohydrates are more toxic than lipids, since high carbohydrate intake is associated with increased risk of total mortality. The molecular, cellular and neuroendocrine mechanisms of carbotoxicity are described, specifically the impact of advanced glycation end-products, high dose fructose and uric acid.

Several types of diet that curb carbohydrate intake, and thus combat carbotoxicity, are reviewed. These include the low-carb diet and the ketogenic diet, in which carbohydrates comprise <20% and 5% of calorie intake, respectively. In addition, the impact of several pharmacological strategies for reducing carbotoxicity are suggested, such as acarbose, SGLT2 inhibitors and metformin. This review is of particular interest in light of the following article (see 12.9).