Dear Mark: Fasting, Training, and Growth Hormone; Wear and Tear on the Arteries

For today’s edition of Dear Mark, I’m answering a couple of questions from the comment sections of the last couple weeks. First, it’s been established that fasting and exercise both raise growth hormone. What about fasted exercise—does that have an even stronger effect? And what about continuing to fast after your fasted workout? Then, I discuss the inevitability (or not) of wear and tear on the arteries from blood flow-induced shear stress. Is shear stress “bad,” or do certain factors make it worse?

Let’s dig in.

Marge asked:

So fasting raises growth hormone levels? Interesting. So does weight lifting. I’ll bet fasted weight workouts would be pretty powerful.

They do, and they are.

What’s even better is to work out in a fasted state and keep fasting after the workout. This keeps the GH spike going even longer. And in my “just so story” imagination—which is actually quite accurate, judging from real world hunter-gatherers—it mirrors the circumstances of our Paleolithic ancestors. You’d get up early to go hunting without having eaten. You’d expend a lot of energy on the hunt. You’d make the kill, procure the food. And then you’d bring it back to camp to finally eat. Maybe you’d pass the heart and liver around the circle before heading back. And sometimes, you just didn’t make the kill. You didn’t eat at all.

Makes sense, right? Fasting, doing something physical, and continuing to fast shouldn’t be a monumental undertaking. It should be well within the realm of possibility for the average person.

Now, I wouldn’t do this all the time. There is such a thing as too much of a good thing. A hormetic stressor can become a plain old stressor if it’s prolonged for too long. Instead, I would throw post-fasted-workout fasting in on an occasional basis.

Nor would I expect huge “gains” from this. Physiological growth hormone production won’t make you huge or shredded. In fact, workout-related increases in testosterone and growth hormone don’t actually correlate with gains in hypertrophy. Instead, I’d expect more intangible benefits, things you won’t notice right away. It’s important in cognition. It helps maintain bone health, organ reserve, and general cellular regeneration. It’s great for burning fat.

Growth hormone does way more than promote overt muscular growth.

Steve wrote:

In the linked article it says:

“Endothelial cell dysfunction is an initial step in atherosclerotic lesion formation and is more likely to occur at arterial curves and branches that are subjected to low shear stress and disturbed blood flow (atherosclerosis prone areas) (7,8). These mechanical stimuli activate signaling pathways leading to a dysfunctional endothelium lining that is barrier compromised, prothrombotic, and proinflammatory.

So it seems that endothelial disfunction comes first, triggered by blood flow stresses. It’s common wear and tear in exposed areas. The patched knees on jeans. Managing endothelial health and healing may slow or diminish rate of progression or is it mostly too late for that?

I’m not a doctor. This isn’t medical advice. This is just speculation.

I find it rather hard to believe that healthy arteries are inherently fragile and prone to damage and incapable of weathering the “stress” of blood flowing through them, even at the “susceptible” curves. I find it more likely that poor health, poor diets, and poor lifestyles make us more susceptible to otherwise normal stresses.

Do the mechanical stimuli weaken the endothelium in people with healthy levels of nitric oxide production? Or are we talking about people whose poor nitric oxide status is exacerbating the damaging blood flow patterns, leaving their endothelium vulnerable to atherosclerosis?

Think about how much context matters in our response to stimuli. If you’re shy around girls, a school dance will be a traumatic experience. If you’re comfortable around girls, a school dance will be a great experience. If you’re weak, lifting a barbell will be scary, and you may injure yourself. If you’re strong, lifting a barbell will be second nature, and you may get stronger. The baseline context determines the quality of the response.

I’d argue that blood flowing through your arteries should be a commonplace occurrence. It shouldn’t be a traumatic experience. Now, maybe I’m wrong. Maybe it is stressful regardless of the baseline endothelial health and the amount of nitric oxide you produce. Maybe it’s just a matter of time. But:

  • We know that, as you quote, atherosclerosis tends to occur at bends and curves of the arteries—the places most likely to be subject to “disturbed flow” patterns.
  • We know that “laminar flow”—blood flowing smoothly through the artery—is protective of the endothelial wall, promoting anti-inflammatory effects and making the endothelium more resistant to damage.
  • We know that “disturbed flow” has an opposing effect on endothelial health, promoting inflammatory effects and rendering the endothelium more susceptible to damage. This increases atherosclerosis.
  • The question I’m wondering is if “disturbed flow” at the curves and bends of the arteries is inevitable or not. And if disturbed flow is always “bad.”
  • We know that hyperglycemia—high blood sugar—makes disturbed blood flow more damaging to arterial walls. Diabetics have higher rates of atherosclerosis because their elevated blood sugar interacts with disturbed blood flow patterns.
  • We know that nitric oxide increases vasodilation in response to shear stress—widening the arteries to accommodate the increased stress and mitigate the damage done. We know that people with hypertension don’t get the same vasodilatory benefits from nitric oxide.
  • We know that “functional increases” of shear stress attained via exercise increase nitric oxide and oxygen production and induce autophagy (cellular cleanup) in the endothelial walls.

That sounds like there are a lot of factors that increases and mitigate the effects of shear stress on the endothelial wall. It sounds like some factors make shear stress more damaging, and some factors make it less. There may even be factors, like exercise, that make shear stress healthy.

This topic is really pretty interesting to me. It deserves a deeper dive, don’t you think?

What about you, folks? What’s your take on fasted workouts and GH secretion? Ever try one?

And do you think your arteries are doomed to fall apart at the seams?


Nyberg F, Hallberg M. Growth hormone and cognitive function. Nat Rev Endocrinol. 2013;9(6):357-65.

Park SK, La salle DT, Cerbie J, et al. Elevated arterial shear rate increases indexes of endothelial cell autophagy and nitric oxide synthase activation in humans. Am J Physiol Heart Circ Physiol. 2019;316(1):H106-H112.

About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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11 thoughts on “Dear Mark: Fasting, Training, and Growth Hormone; Wear and Tear on the Arteries”

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  1. Genetics plays a huge factor. The men in my family tend to have heart attacks in their 40’s and 50’s despite none of the typical risk factors such as diabetes, smoking, obesity, high cholesterol, poor diet. We’re healthy and we drop dead early – I struggle with how evolutionary adaptation works in this regard.

    1. The issue is that evolution wouldn’t really do anything to weed out your specific flaw.

      Since 40-50 is well past prime baby making years (though men could keep making babies, they often weren’t living that long anyway), it wasn’t a big deal historically if you were dead. Your kids were already born and maybe even some grandkids. So if you died, it didn’t do anything to stop your genes from continuing down the line.

  2. I do 4-5 fasted workouts per week, usually lifting with some high-intensity intervals mixed in. For the first month or so, about a quarter of the workouts were of subpar energy. Since then, I’ve noticed little difference between fasted and fed workouts.

    With respect to your comment on hormetic stressors, if I am eating eggs 75-90 minutes after a fasted workout, am I crossing the line between hormetic and plain stress given the 4-5 instances per week?

    1. I actually do worse with a fed workout. Makes me feel sluggish, even 3 hours after eating.

  3. All my workouts are in the mornings and are fasted, even my sprint sessions. Works really well for me. I usually eat about an hour afterwards. Once in awhile I’ll start a 1-2 day fast with a workout and feel great.

    Question for Mark: How about hypoglycemia as opposed to hyperglycemia, being damaging to arterial walls?

  4. This is an unrelated question I’m hoping you will answer (and I’m sorry if you’ve answered it before). Can one ingest TOO much collagen? I make my own bone broth from pastured animals(I don’t drink it daily-used in soups and cooking so 1-2 cups per week), I take collagen capsules daily (6000mg), and am looking to use a powdered form in my coffee or smoothies. Would that be overdoing it?

  5. I’m quite curious as to how fasting long after a workout will affect muscle protein synthesis personally. Sometimes I do so after an intense run or weights workout.

    1. Within 24 hours? Not much

      Nothing to worry about if you’re not body building for pure mass/muscle.

  6. I think that if you’re going to be sitting for a while then it’s probably healthier to have a cushioned surface. I figure that it reduces your chances of blood vessel damage and thrombosis by taking stress off blood vessels and preventing you from squishing them.
    I’ve noticed since the start of the school year last September that ripped jeans are really popular among the girls in high school. I wonder how much extra those cost?

  7. Thank you, Mark! Great to have confirmation on the GH benefits of fasted workouts! I have generally found it more comfortable to do either cardio or weight workouts on an empty stomach, and it is nice to know that there is more to it than just comfort…

  8. I think that veins moved into an artery location are doomed to fall apart, no matter what you do. Because venous blood pressure is typically much less than artery. Simple mechanics.

    I think that we’re focusing on the epithelial cells and forgetting the connective tissue it lives in/on. All of that, and its flexibility depends on our Vitamin C status. No Vitamin C, or too low, and there’s not enough to rebuild everything that needs rebuilding (out of collagen), especially for athletes.

    I don’t think shear is a big issue until a person is old enough to have worn down their ability to make enzymes to keep up repairs. But a person can be prematurely old by having a low vitamin status, since they play a big part as cofactors in enzyme functions.

    I think a civilized nation doesn’t just make sure its citizens have filled bellies, it makes sure the food available to everyone is the highest in vitamins it can be. By that standard, chemical fertilizers would’ve been abandoned as a bad idea as soon as they were first proposed.