JG. Green, NA. Johnson, T. Sachinwalla, CW. Cunningham, MW. Thompson and SR. Stannard (2010). Low-carbohydrate diet does not affect intramyocellular lipid concentration or insulin sensitivity in lean, physically fit men when protein intake is elevated. Metabolism: clinical and experimental, 59(11), 1633-41. https://doi.org/10.1016/j.metabol.2010.03.013

PubMed 20423743

[Abstract]
It has been speculated that dietary carbohydrate restriction is solely responsibly for mobilization of endogenous lipid stores, elevation of plasma free fatty acid (FFA) concentration, and an associated reduction in insulin sensitivity seen in starvation and low-carbohydrate diets. In 6 healthy men, dietary carbohydrate was eliminated but gluconeogenic substrate supply was maintained by 3 days of very low-carbohydrate/high-protein (HPLC) diet. Results were compared with 3-day starvation and 3-day mixed-carbohydrate diet. Intramyocellular lipid (IMCL) concentration was measured by ¹H magnetic resonance spectroscopy, and insulin sensitivity was determined by intravenous glucose tolerance test. Fasting plasma glucose was significantly reduced ([starvation] 3.5 ± 0.3 vs [HPLC] 4.2 ± 0.4 and [mixed] 4.5 ± 0.3 mmol L⁻¹, P < .01), and IMCL to water ratio (25.6 ± 5.9 vs 13.6 ± 6.1 and 13.6 ± 3.3 × 10⁻³, P < .01) and fasting FFA (1179 ± 294 vs 387 ± 232 and 378 ± 120 μmol L⁻¹, P < .05) were significantly elevated after starvation but were unchanged after HPLC. Minimal model insulin sensitivity was reduced after starvation (5.7 ± 1.5 vs 14.5 ± 4.8 and 16.5 ± 6.8 L min⁻¹ mU⁻¹, P < .05). Plasma glucose, plasma FFAs, IMCLs, and insulin sensitivity are maintained when an HPLC diet is consumed, despite other forms of carbohydrate deprivation producing marked changes in these measures. We conclude that dietary carbohydrate restriction does not cause circulating FFA to become elevated. However, it remains possible that circulating carbohydrate status has an important influence on plasma FFA and therefore insulin sensitivity in healthy people.