When early humans ate meat sporadically and had little access to carbohydrates, the liver became less responsive to insulin to ensure the brain got enough glucose. Today, with constant carbohydrate...
Mechanism
Synthesis from 1 study
When people ate mostly meat and rarely got carbs, their livers learned to make glucose from protein and turn fat into brain fuel, so the brain always had energy. But now that we eat carbs all the time, the liver keeps making glucose and fat even when it’s not needed, which leads to high blood sugar...
Most probable mechanism
When there's little sugar in the diet, the liver stops responding to insulin so it can make its own glucose from protein, while also turning fat into alternative brain fuel. This keeps the brain supplied with energy even when food doesn't provide carbs. But when carbs are always available, the liver keeps making glucose and fat anyway, which overloads the system and leads to high blood sugar and fat buildup.
Low dietary carbohydrate intake reduces circulating insulin levels
Reduced insulin signaling de-represses gluconeogenic enzymes in the liver and suppresses lipogenic enzymes
Amino acids from dietary protein are converted into glucose via gluconeogenesis and released into circulation to maintain cerebral glucose supply
Free fatty acids are mobilized from adipose tissue and transported to the liver for beta-oxidation
Excess acetyl-CoA from fatty acid oxidation exceeds TCA cycle capacity and is diverted into ketogenesis
Ketone bodies are synthesized in hepatocytes and released into circulation to serve as alternative fuel for the brain and other tissues
Elevated ketone bodies inhibit histone deacetylases, increasing expression of stress-resistance genes that enhance cellular resilience
Gut microbiota shift from fiber-fermenting to protein-fermenting species, producing metabolites that enter systemic circulation
Dietary carnitine and choline from meat are metabolized by gut bacteria into trimethylamine, which is oxidized in the liver to trimethylamine-N-oxide
High gastric acidity and proteolytic enzyme activity enable efficient protein digestion and pathogen defense
Solid meat particles are retained in the stomach to allow prolonged mechanical and chemical digestion, delaying nutrient delivery
Reduced salivary amylase activity limits pre-gastric starch breakdown, reflecting evolutionary adaptation to low-starch diets
Evidence from Studies
Supporting (1)
Community contributions welcome
Human Digestive Physiology and Evolutionary Diet: A Metabolomic Perspective on Carnivorous and Scavenger Adaptations
Contradicting (0)
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