The 'membrane pacemaker theory of aging' suggests that within a single species, a higher metabolic rate is actually associated with a longer lifespan, challenging the idea that a slower metabolism is always better.

A lot of foundational biochemistry, including common metabolic pathways, is derived from animal models and may not accurately reflect human physiology in a clinical setting.

Burning fat is less efficient than burning glucose because it produces a higher ratio of FADH2 to NADH, leading to reverse electron transport and increased reactive oxygen species.

Long-term adherence to low-carb diets can be inherently stressful on the body, potentially leading to issues like anxiety, poor sleep, hormonal imbalances, and eventual weight regain.

In conditions like heart failure and type 2 diabetes, the heart's reliance on fat for energy actually increases, which is associated with impaired mitochondrial function rather than improved health.

A 2023 study on keto-adapted women showed that introducing a high-carb diet for 21 days caused their inflammatory markers and other health biomarkers to worsen significantly.

A new research perspective proposes viewing ketosis as the normal human metabolic state and studying the addition of carbohydrates as a 'perturbation' to that baseline.