What is AMPK and how do you activate it (through fasting or exercise)?
Both fasting and intense exercise reliably activate AMPK, with high exercise intensity producing the strongest effect. If you want to activate AMPK, intense exercise is your most concrete lever.
AMPK is an enzyme that acts as the cell's energy meter. When a cell has less ATP (the cell's fuel), the ratio of the breakdown products AMP and ADP relative to ATP rises. That signal switches AMPK on. It is one of the central switches for energy regulation in the body.
Once AMPK is active, it does two things simultaneously. It prompts the cell to burn fats and glucose to generate new energy. At the same time, it inhibits processes that consume energy, such as the production of new proteins or fats. In this way the cell tries to restore its balance. In addition, AMPK steers the health of the mitochondria (the cell's energy factories) and stimulates autophagy: the clearing out and recycling of damaged cellular components.
Exercise is one of the most powerful ways to activate AMPK. Muscle work consumes large amounts of ATP, which rapidly disrupts the energy balance in muscle cells. High-intensity exercise leads to noticeably stronger AMPK activation than low-intensity exercise. In well-trained athletes, high-intensity cycling was also found to substantially trigger autophagy in muscles, whereas low intensity barely did so.
Fasting works through the same principle: when the cell receives less fuel, energy reserves fall and AMPK switches on. This also triggers autophagy. The available studies do not specify an optimal fasting duration; the focus is on the mechanism, not on a concrete schedule. Interestingly, combining fasting and high-intensity exercise did not amplify the autophagy response in that athlete study beyond what exercise alone achieved.
AMPK is being intensively investigated as a target for drugs against type 2 diabetes, obesity, inflammation and cancer. Pharmacological compounds that activate AMPK directly or indirectly already exist. Directly acting agents bind to a specific site on the AMPK protein; indirect agents mimic the energy deficit that fasting or exercise also causes. This is, however, still largely a research domain: for most applications the therapeutic promise exists, but a proven treatment in humans does not.
This answer draws on multiple review articles on AMPK biology and activation, supplemented by a smaller study in trained athletes on exercise and autophagy. The basic functioning of AMPK as an energy meter and the effects of exercise and fasting are well documented and consistent. Evidence for therapeutic applications in humans is far less concrete: the review articles speak of "potential" and "pursued targets," not of completed clinical proof.
Is brown fat really different from regular fat, and can I activate it?
Brown fat is genuinely different from regular fat and you can activate it, with cold exposure having the strongest evidence. Supplements and medications do not yet exist, but spending time in a cooler environment regularly is a concrete, achievable step.
What does your thyroid do to your metabolism and energy?
Your thyroid is one of the most powerful regulators of your resting metabolism, and both too little and too much hormone has measurable consequences for weight, heart and metabolism. If you suspect your thyroid is not functioning properly, a blood test at your GP is the logical first step.
Does coffee activate mTOR?
Caffeine inhibits mTOR in cell and animal research, but coffee as a complete drink actually activated mTOR in the muscle tissue of mice. What exactly happens in humans has not yet been studied, so no practical conclusions should be drawn from this yet.
What is NAD+ and what does it do in your body?
NAD+ is an indispensable molecule for energy, DNA repair and cell health, but the question of whether you should actively raise those levels for better health has not yet been answered for humans.
Does fasting or intermittent fasting help prevent cancer?
There is no evidence that fasting prevents cancer in humans; the animal results are promising but contradictory. If you want to address excess weight as a way of reducing risk, intermittent fasting can be a tool for that, but do not expect a direct cancer-preventive effect.
Does fasting reset your immune system?
Fasting lowers inflammatory markers and improves metabolic risk factors, but a true 'reset' of the immune system has not yet been firmly demonstrated. The strongest gains are in weight and blood pressure; for specific immune diseases it is still too early for conclusions.