“Starvation Signals: How AMPK Helped Me Survive Vietnam”
A molecular reflection on trauma, energy, and endurance.
Everything in my life feels like it’s moving in reverse. I was born into generational wealth in Vietnam, but when I was 8½ years old, the fall of Saigon erased all of it. Most people spend their lives accumulating wealth and maintaining their health in the second half of their lives. For me, the journey started with profound loss and scarcity, and a cellular survival response that may have saved my life because my AMPK pathway was activated at an early age.
AMPK: The Starvation Switch
AMPK is a cellular energy sensor, like a biochemical thermostat. It activates when energy levels are low, such as during fasting, illness, or trauma. In most people, AMPK declines with age. But for me, it was activated early, triggered by extreme stress, trauma, and starvation.
And that early activation mattered.
AMPK regulates energy by: Turning on energy-generating processes (like fat burning and autophagy), turning off energy-consuming growth pathways (like mTOR). This is how cells prioritize survival over growth.
Typically, AMPK activity decreases in the second half of life. It plays a crucial role in many age-related diseases. Why is AMPK activity dampened when we age?
Mitochondrial dysfunction is a primary reason. As we age, we have fewer mitochondria, resulting in reduced ATP turnover, which in turn leads to weaker activation of AMPK.
Chronic low-grade inflammation is another factor in weakening our AMPK pathway. Inflammaging activates NF-κB, which is like a fire alarm system inside your cells. When your body detects stress, infection, toxins, or damage, it sets off this alarm.
Living in 2025, where toxins are present in our water, in the air, and in our food supply chain, as well as 5G radiation, you might want to think that there is a conspiracy theory that some group of people is creating this environment to kill us. Nah, that would be too much of a stretch to think like that. This environment weakens our AMPK pathway.
AMPK, the metabolic master switch, doesn’t thrive in luxury. It’s awakened by hardship, fasting, movement, and discipline. With aging, there is an imbalance between AMPK and mTOR.
For my path, with my AMPK pathway being turned on at an earlier age, it helps with my health. Early-life AMPK activation lays down a metabolic foundation that protects mitochondria, enhances immune function, suppresses tumor growth, and extends healthspan.
AMPK was activated in me not by choice, but by circumstance, trauma, running from the Malaysian military, starvation, and relentless adaptation. This biochemical adversity became a hidden strength.
The LKB1 Link: Building Order in Chaos
LKB1 is a tumor suppressor that also activates AMPK, not shown in the first diagram. It helps maintain cell polarity, ensuring that each cell knows its position and function, much like the bricks in a wall. If LKB1 is lost, the bricks rotate or fall out of line, causing the wall to collapse. This is how cancer spreads.
In me, LKB1 did its job early. It helped preserve structure under extreme stress, maintained cell order, and initiated metabolic checkpoints.
AMPK Turns on Autophagy
ULK1, a protein downstream of AMPK, initiates autophagy, the cleanup crew that recycles damaged mitochondria and proteins. During trauma and fasting, this pathway helps cells survive by removing garbage and reusing nutrients.
AMPK also shuts off ACC (Acetyl-CoA Carboxylase), the first enzyme in fat synthesis, and HMG-CoA reductase (responsible for cholesterol production). When energy is scarce, the body doesn’t waste resources storing fat; it burns it instead by activating ATGL. One of the products of Fatty acid metabolism is Ketones. That’s survival biochemistry.
AMPK also inhibits Glycogen Synthase (GS) by phosphorylating it. During energy stress (when AMPK is activated), the body doesn’t want to store glucose as glycogen; it wants to burn it to make ATP. Thus, AMPK shuts down glycogen storage to prioritize efficient energy utilization over energy storage.
In diabetes or insulin resistance, the body doesn’t respond well to insulin, so the enzyme glycogen synthase (GS) doesn’t work correctly. This means that instead of storing extra glucose as glycogen (your body's energy reserve), the glucose remains in the blood, leading to high blood sugar levels. Activated AMPK shuts this down.
In cancer, tumor cells rely on a process known as the Warburg effect, where they metabolize glucose for energy without utilizing oxygen, even when oxygen is available. This is less efficient than using the mitochondria (which burn glucose with oxygen), but it allows the cancer cells to grow and divide much faster. When AMPK is activated, it shuts down sugar-burning for growth and prompts the cell to generate energy cleanly and efficiently through the mitochondria.
Because of this shift, the cancer cells don’t bother storing glucose as glycogen, which is what glycogen synthase (GS) does. Storing energy isn’t a priority.
What Cancer Does Differently
Cancer cells flip the script: they turn off AMPK, removing the brake on cellular growth. It avoids energy stress and continues to produce DNA, lipids, and proteins to support its rapid growth and cellular division. It suppresses autophagy, allowing damaged parts to persist. Without AMPK, cancer cells activate glycolysis (the Warburg effect), allowing them to grow rapidly using glucose while avoiding the use of mitochondria.
This reprogramming gives cancer cells an advantage, but at the cost of order and integrity.
Little AMPK…hold my beer.
If you look at the upper right section of the above diagram, you can see that there are several AMPK ACTIVATORS (Top Right):
Metformin
Phenformin
AICAR (experimental drug)
Quercetin
Berberine
EGCG
Other Pathways Activated By AMPK:
If you think of AMPK as a train station, look straight down and see the track where it turns on PGC1. This enhances mitochondrial biogenesis and oxidative metabolism, and activates NAD+, which synergizes with SIRT1 (deacetylation) and FOXO.
PGC-1α is like your body’s personal trainer for energy production. It signals cells to build more mitochondria and ramp up fat and sugar burning for fuel. This process is essential for boosting endurance and metabolic efficiency. PGC-1α works even more effectively when paired with SIRT1, which is activated by NAD⁺ and triggered during fasting, resulting in enhanced mitochondrial function and cellular resilience.
FOXO transcription factors act as cellular survival coaches. They activate genes that increase resistance to oxidative stress, promote DNA repair, and support longevity. When AMPK is activated, such as during fasting, exercise, or energy stress, it stimulates both PGC-1α and FOXO pathways. Together, they create a synergistic response that boosts metabolic health, slows the aging process, and enhances the body’s ability to withstand disease and cellular damage.
In cancer, tumors often shut down AMPK to bypass the body’s energy checkpoints, allowing uncontrolled growth through persistent mTOR activation and sustained lipogenesis, which facilitates the building of new cell membranes. This is especially common in cancers with LKB1 mutations, such as lung and cervical tumors, which disable the normal activation of AMPK.
However, this vulnerability creates an opportunity: reactivating AMPK using agents such as metformin, Berberine, Dichloroacetate (DCA), and fasting protocols can help restore cellular energy sensing, suppress tumor progression, and re-engage natural growth suppression mechanisms.
From a longevity and metabolic terrain perspective, AMPK activation mimics the benefits of caloric restriction. It promotes fat burning, boosts autophagy, enhances mitochondrial function, and counters the aging-related overactivation of mTOR that drives cellular stress and degeneration. These benefits lie at the heart of therapies such as ketogenic diets, intermittent fasting, and plant-based polyphenol supplementation.
Final Reflection
So, whether you’re outsmarting cancer, outliving inflammation, or just outpacing Father Time, remember this: AMPK is your cellular survival switch; your body’s built-in biohacker. Feed it with fasting, fire it up with mitochondria-loving molecules, and let it do what it was designed to do: keep you lean, clean, and disease-resistant. In a world hooked on excess, AMPK is your minimalist mentor whispering: “Do more with less, and live better longer.”
Anthony Phan MD
Thank you Dr. Phan.
So I would assume that those with the loss of LBK1 that it would be important to avoid extreme stress if possible?
Also, what do you think of NAD+ oral supplements?
Great article. I cannot have metformin or berberine, but I do have quercetin. Right now I am in good health but I will keep that in mind !