Why You're Frozen in Survival Mode: Understanding CDR

September 02, 2026

In this episode of the Health Optimization Medicine Podcast, Dr. Allen Bookatz, Dr. Scott Sherr, Jodi Duval, and Dr. Ted Achacoso explore:

Why can persistent fatigue and brain fog represent an ongoing cellular defense response rather than simply a lack of energy?
How does the Cell Danger Response change mitochondrial energy production and signaling, and why can cells remain in a defensive state even after the original threat has passed?
Why can pushing harder with caffeine, intense exercise, NAD boosters, or other interventions backfire when the body is still responding to danger signals?
How can exposomic unburdening, metabolomic testing, and targeted molecular support help create the conditions for cells to move from defense toward recovery?
What role do circadian timing, autonomic regulation, sleep, and appropriately graded activity play in signaling safety and allowing the Cell Danger Response cycle to resolve?

What We Discuss:

00:00 – When the Cellular Alarm Won't Turn Off
03:00 – The Three Phases of the Cell Danger Response
03:39 – How Environmental Stress Signals Affect Cellular Energy
04:21 – When ATP Becomes a Danger Signal
05:16 – Why More Exercise and NAD+ May Backfire
06:45 – The Three-Phase Recovery Approach
09:30 – Do This on Monday Protocol: Keep an Energy Log
10:26 – The Case Against the Cell Danger Response Model
12:21 – Three Takeaways for Cellular Recovery
13:13 – From Fighting Disease to Creating Health
13:41 – Clinical Metabolomics, Exposomics & Cellular Bioenergetics

Full Transcript:

Dr. Allen Bookatz (00:00:00):
What if your fatigue and brain fog are not proof that your body's broken, but evidence that your cells are still protecting you from a threat that no longer is there? During infection, toxin exposure, or tissue injury, shutting down normal energy priorities can be the correct survival move. The problem begins when the crisis ends but the cellular alarm keeps ringing. Today, we're gonna talk about why the body gets stuck, why pushing harder can backfire, and how to make "you are safe now" mean something at the level of the cell. This is the Health Optimization Medicine podcast. I'm Dr. Allen Bookatz, chief of emergency medicine and a health optimization medicine doctor. With me, we have Dr. Scott Sherr, who's our COO of HOMeHOPe and health optimization practitioner, Jodi Duval, naturopathic doctor and health optimization medicine practitioner, and Dr. Ted Achacoso, founder of Health Optimization Medicine and Practice, who's agreed to translate complex mitochondrial biochemistry into complete sentences for the rest of us.

Dr. Ted Achacoso (00:01:05):
Well, Allen, I agreed to complete sentences, but I made no promises about short ones.

Dr. Scott Sherr (00:01:11):
Dissertation's probably coming soon.

Jodi Duval (00:01:13):
We brought a stopwatch, so.

Dr. Scott Sherr (00:01:16):
And a metabolic map, too. In the next 25 minutes, what freezes a Cell Danger Response, what the evidence can and cannot tell us yet, and a practical three-phase way to think about recovery.

Dr. Allen Bookatz (00:01:26):
Okay, good. Let's unfreeze something.

Dr. Scott Sherr (00:01:28):
Here's the $64,000 question. A patient has seen 10 specialists, collected a small pharmacy of anti-inflammatories, and developed a caffeine habit that could power a regional airport. Yet the post-viral or post-mold-related fatigue barely moves. Why, Jodi?

Jodi Duval (00:01:44):
Well, because more energy may be the wrong instruction. If the biological network still reads danger, then low energy output can be an adaptive decision for protection, so not simply a missing ingredient.

Dr. Allen Bookatz (00:01:59):
That's super insightful, Jodi, 'cause that distinction really matters. We see this in the ER all the time. The acute version's pretty obvious here, right? We have sepsis. We have shock. We have trauma. We have different toxic exposures, and we see this play out in real time where the body diverts resources towards survival. I think the chronic CDR picture is much quieter, so the crisis has already passed, but the parking brake is still very much on.

Dr. Scott Sherr (00:02:25):
And these massive amounts of stimulants, this caffeine habit, et cetera, this is all the gas pedal, right?

Dr. Allen Bookatz (00:02:30):
Exactly. It's like almost you're pushing both pedals at once and making a lot of noise, heat, and you're making your transmission very unhappy.

Dr. Ted Achacoso (00:02:40):
Well, at the cellular level, mitochondria are not merely batteries. They are threat sensors and signaling hubs. Under danger, oxidative phosphorylation and ATP handling change. ATP released outside the cell participates in purinergic danger signaling. This response recruits inflammation and alters cellular behavior.

Jodi Duval (00:03:00):
And then healing has an order, so CDR1, defense, CDR2, proliferation and repair, and CDR3, differentiation and reintegration. So you do not negotiate with biology by skipping directly to peak performance.

Dr. Scott Sherr (00:03:17):
So, Dr. Ted, root cause is necessary but still incomplete, yeah?

Dr. Ted Achacoso (00:03:21):
Correct. Pathogenesis asks for root causes of disease. Salutogenesis asks for root causes of health. Remove what sustains danger and restore what permits the network to become healthy again.

Dr. Scott Sherr (00:03:32):
Okay. You ready, Jodi? Let's go one level deeper here. A gut-derived or environmental stressor arrives. What happens? Go.

Jodi Duval (00:03:39):
Well, the signals associated with the mycotoxins that we're seeing and sensing, microbial products and lipopolysaccharides or tissue damage can activate these innate immune and purinergic pathways. So the mitochondrial membrane potential redox balance and then the fuel use shift, the usage of all of these move in different directions. ATP released through channels, including connexins, can become extracellular ATP, and that's in the local alarm system or signal.

Dr. Allen Bookatz (00:04:10):
So are you saying that ATP has two lives then, right? One that lives inside the cell and, sounding like it, it's currency, and then outside the cell it acts as a siren?

Dr. Ted Achacoso (00:04:21):
Yes, precisely. Location changes meaning. Intracellular ATP says work can proceed. Extracellular ATP can say something was injured here. Through P2X and P2Y receptors, that message propagates across a tissue network.

Dr. Scott Sherr (00:04:36):
Which explains the mismatch, right? Normal routine labs, but extremely abnormal lived experience.

Dr. Ted Achacoso (00:04:43):
Yes, routine laboratory tests are excellent for established pathology, but they do not comprehensively describe cellular function. No diagnosable disease on this panel is not identical to optimal health. Preventive medicine remains organized around preventing disease. Health optimization measures and tunes the conditions of health.

Dr. Allen Bookatz (00:05:01):
That's also why "it's all in your head," which so many of our patients and clients hear, is probably such a poor conclusion. Sometimes the problem is not imaginary in this case, and the measurement window that we're looking at is just too coarse.

Jodi Duval (00:05:16):
That's right, Allen, and then the intervention also can be too coarse. So we look at generic high-intensity exercise. It sounds healthy until a patient or client has post-exertional malaise. And a prescription becomes precise only when it is matched to their current biological capacity.

Dr. Scott Sherr (00:05:36):
Capacity is so important here, right? The longevity version of the same mistake actually is throwing NAD boosters, rapamycin, and another fashionable molecule at a network that is still defending itself.

Dr. Ted Achacoso (00:05:48):
Yes, like getting an NAD infusion after a night at a Las Vegas casino, right? So lifespan without healthspan is merely a longer calendar. The goal is to extend biological peak quality of life. If danger signaling remains active, adding another lever may not restore coherence and can add another variable to an already noisy system.

Dr. Allen Bookatz (00:06:09):
Medicine's favorite hobby, turning one unexplained variable into 12.

Jodi Duval (00:06:14):
And then 12 separate bottles.

Dr. Scott Sherr (00:06:17):
And separate prescriptions. The Health Optimization Medicine Conference is happening. Two days of events, October 2nd and 3rd, Chicago, Illinois, at the Drake Hotel. CMEs available to practitioners who need them. Just 150 people with amazing speakers on the cutting edge of health and wellness. This is a community. It's not your average conference. If you're interested, go to homehope.org and save 25% on your ticket by using conference25 at checkout. I hope to see you there.

Dr. Allen Bookatz (00:06:45):
Let's earn the practical part here. So how do we walk a patient from a persistent defense towards this bioenergetic flexibility we're talking about?

Dr. Scott Sherr (00:06:54):
So the HOMeHOPe one-cent solution actually has three phases in this case, not three magic tricks, three clinical jobs. Jodi, you wanna lead us off here?

Jodi Duval (00:07:02):
All right. So first we've got the exposomic unburdening. So ask what is still telling the system that danger is present. So you're looking at water-damaged buildings, relevant microbial exposures, dietary antigens, gut barrier dysfunction, and endotoxin translocation. That may all matter in the right patient or client. So you cannot convincingly signal safety while the smoke is still coming through the door.

Dr. Allen Bookatz (00:07:29):
This rings true to home. So if I'm cooking and the fire alarm goes off, I just take the alarm battery out, and problem solved. So you're saying don't begin by removing the alarm battery here. Maybe look for the fire, the thing that started it in the first place?

Dr. Scott Sherr (00:07:46):
You'd think. Novel. Dr. Ted, next one.

Dr. Ted Achacoso (00:07:51):
Second, assess intracellular and metabolic function, then provide targeted molecular support. Organic acids, acylcarnitines, redox markers, amino acids, and micronutrient patterns can reveal constraints in the Krebs cycle, fatty acid transport, methylation, and antioxidant systems.

Dr. Scott Sherr (00:08:09):
And this is where measured, not fashionable, actually matters, Dr. Ted, yes?

Dr. Ted Achacoso (00:08:14):
Exactly. I have patients asking me, "Should I take NAD?" No, actually you have to measure all of this, like active B vitamins, magnesium, CoQ10, glutathione support, membrane lipids. These are not a universal shopping list. The intervention follows the measured network. Orthomolecular means the right molecule in the right form for the right biological context.

Dr. Allen Bookatz (00:08:39):
Oh, wait, so no supplement confetti?

Dr. Ted Achacoso (00:08:41):
Hey, confetti's difficult to dose.

Dr. Allen Bookatz (00:08:45):
Fair point.

Dr. Scott Sherr (00:08:46):
All right, let's talk about phase three here. So phase three is important, too. Reinforce safety through circadian timing, autonomic regulation, graded activity, sleep, and of course membrane support, which we've talked about before. Morning outdoor sunlight actually helps anchor circadian timing. Carefully selected autonomic interventions, including breathwork practices or, where appropriate, even transcutaneous vagus nerve stimulation, I know Allen likes the one on his neck, may support parasympathetic flexibility. Movement must be respected, by way of what is their current capacity.

Jodi Duval (00:09:19):
And the sequence is also the message. So removing the continuing insult, restore molecular terrain, and then you expand capacity without triggering another crash.

Dr. Allen Bookatz (00:09:30):
Okay. So let's talk about our Do This on Monday action plan. So for one week, let's stop treating fatigue as a character defect, okay? Let's keep a simple exposure energy log, so sleep timing, morning light, meals, environments, exertion, symptoms, and recovery time. Look for the repeatable trigger crash pattern, then replace one indiscriminate push, like extra caffeine or some punishing workout, with one safety-supporting action.

Dr. Scott Sherr (00:10:03):
Would this be something like morning light, Dr. Allen?

Dr. Allen Bookatz (00:10:06):
Yes, absolutely. Sunrise would be my, we'll call, aspirational answer here, but if we can get within 30 minutes of waking, then I think that should be good enough.

Jodi Duval (00:10:17):
So when will we we will accept biological consistency over theatrical heroics?

Dr. Scott Sherr (00:10:26):
And some of us like theatrical. But okay, this is the part where we talk about steel man, right? So it's time to argue against ourselves, ladies and gentlemen. What is the strongest conventional critique of the Cell Danger Response framework, Allen?

Dr. Allen Bookatz (00:10:41):
Okay. First off, it's a pretty broad mechanistic model, and when we look at broad models, they become unfalsifiable even if a chronic symptom is interpreted through them. So think of it like the biology of purinergic signaling. It's real, but a large prospective trial that links specific CDR stage measurements to standardized measurements in patient outcomes is really limited.

Jodi Duval (00:11:06):
And a critique would also say that metabolic patterns can be influenced by diet and timing, medications, collection methods, and analytic platforms. So complex individualized protocols are harder to standardize than a single drug directed at a defined target. So it is tricky.

Dr. Scott Sherr (00:11:24):
Are these fair criticisms, Dr. Ted? What do you think?

Dr. Ted Achacoso (00:11:27):
Well, we should welcome them. A framework is useful only if it improves what we measure, what we predict, and what we do. Where evidence is strong, say so. Where it is mechanistic, observational, or is still emerging, say that, too.

Dr. Allen Bookatz (00:11:41):
Let's print that on every conference badge that we go to.

Dr. Ted Achacoso (00:11:46):
HOMeHOPe uses evidence-informed clinical care or evidence-informed medicine for a network of cells within one person that doesn't replace acute care, antimicrobial treatment, surgery, or disease-specific therapy. It asks one additional question. After the immediate threat is controlled, have we restored the cellular conditions that will meet recovery?

Jodi Duval (00:12:08):
Ted said the model is not permission to explain everything, which is good. It's a disciplined way to test whether persistent danger signaling, metabolic constraint, and incomplete recovery are part of this patient's story.

Dr. Allen Bookatz (00:12:21):
Okay. Well, let's do our take-home three here. So three takeaways short enough to remember without a full metabolomics panel. Jodi, lead us off.

Jodi Duval (00:12:30):
All right. So number one, fatigue can be an active defense program. Repeat after me: not weak willpower, so ask what signal the mitochondria may still be obeying.

Dr. Scott Sherr (00:12:42):
Yes. And two, you cannot reliably stimulate your way out of persistent danger signaling. More gas does not release the parking brake.

Dr. Ted Achacoso (00:12:51):
And three, salutogenesis means removing continuing triggers, measuring the cellular network, restoring missing conditions, and allowing the CDR cycle to finish.

Dr. Allen Bookatz (00:13:02):
So the war is over. The biology just needs its credible orders to stand down.

Jodi Duval (00:13:07):
The signals are in, Allen. Someone tell them. Tell them.

Dr. Allen Bookatz (00:13:12):
The war's finally over, man.

Jodi Duval (00:13:13):
Thanks. All right. So deeper shifts really are from fighting disease alone to creating the conditions of health. And so unburden the exposome, restore metabolic and membrane function, rebuild circadian and autonomic coherence. And when the biological network receives this credible signal of safety, the war is over, energy is no longer forced, it becomes available.

Dr. Allen Bookatz (00:13:40):
Well said, Jodi. So thank you everyone for listening to the Health Optimization Medicine podcast. If you're a physician, healthcare practitioner, or health advocate ready to move beyond disease management and learn clinical metabolomics, exposomics, and cellular bioenergetics, join the HOMeHOPe Clinical Certification Program at homehope.org. That's homehope.org. See you next week.

Dr. Scott Sherr (00:14:05):
Bye.

Jodi Duval (00:14:05):
Take care, everybody.