Autophagy and Collagen

I’m not a proselytizer. I hold positions based upon the available information, at least in my limited understanding of it, but I don’t need others to believe it to satisfy some insecurity. I will write about things like statins (which along with GLP-1s are miracle drugs that have unfathomable amounts of evidence on their side) because I think this might be useful for those truly curious, but if someone doesn’t agree, that’s okay.

As information evolves and changes I constantly reassess and change positions if appropriate. For instance a recent RCT on sucralose made we switch to different non-nutritive sweeteners.

In any case, here are two things I subscribe to that are admittedly on the fringe and perhaps not soundly proven, and for whom many of the people who I admire and respect actually discount.

These are my confession to quack beliefs.

Autophagy and Fasting

I went for a morning bike ride last Sunday. At that point I was 12 hours into a “fast”¹.

I woke up feeling great, and seeing the weather was ideal I hopped on the bike and went for a ride before the house woke. I consumed zero power bars or energy drinks before heading out or during the ride, though I did drink a black coffee with an aspartame² and two drops of stevia sweetener.

30km later – the first half heading downhill, ending at the lake where I admired the view for a moment and then started the trip back uphill – I returned home. Still feeling fantastic. I could have done 30km more.

I then continued to “fast” for four+ more hours. No exhaustion or tiredness hit, and it was a great morning. Finally I enjoyed a moderate lunch. And through the classic “absence makes the heart grow fonder” thing, I enjoyed lunch more than I would have if it was just another meal.

The point of this is that there is a common belief that our bodies have some tiny tank of energy we need to constantly be topping up, culminating in the absurd “breakfast is the most important meal of the day!”³ foolishness⁴. We actually have enormous energy reserves in the form of muscle and liver glucose storage, but our body can then lean on other sources of energy when that is exhausted.

Which is where autophagy comes up.

Your body has two primary “modes”: mTOR and AMPK. mTOR is the “building” phase, while AMPK is the “harvesting” stage. Both are constantly active to some degree, though they are somewhat in opposition such that when mTOR dominates, AMPK is minimal, and vice versa⁵.

mTOR is triggered by proteins, primarily leucine. mTOR also requires robust glucose reserves. When you’re constantly stuffing your face, mTOR runs endlessly.

AMPK is triggered by glucose exhaustion, and turns on catabolic pathways to generate ATP to fuel cells.

AMPK also triggers autophagy, which is Greek for “self-devouring”. Autophagy is a process where your body destroys malformed cells and misfolded proteins, recycles old mitochondria, and so on. It is the recycling and cleanup process – burning the junk for energy – and is considered important for cellular health and longevity.

Autophagy is a natural, necessary process the body performs.

Yet in our “constantly feeding / snacking / consuming sucrose” norms it’s at minimal levels. With your body in an endless cycle of digestion and glucose excess, we minimize this hugely beneficial process, to our detriment.

Daily fasting – having a window where you let your digestive system take a break – has a secondary benefit that with a smaller window to eat, it is much easier to keep calories under control. If you manage to not consume calories for 16 straight hours of the day (remember that probably most of those hours will be while sleeping, and this is not at all hard to do) – 16/8 fasting – it’s much harder to overeat during the remaining 8 hours, and a number of studies have soundly confirmed this.

There’s a myth that people will just gorge during the feeding window, but that isn’t a reality for most⁶. Nor does your body suddenly go into starvation mode where it magically harvests calories from the air and spontaneously builds fat.

16/8 (ideally 18/6) fasting is beneficial for insulin moderation and as a rudimentary caloric intake gate, and to some small degree — especially when coupled with exercise – can increase autophagy.

Not everyone agrees. I’m a big fan of Dr. Norton, but the paper he cites wasn’t even on the topic he focuses on – it was actually comparing fasting versus non-fasting where the combined caloric intake was purposefully homogenized across groups to see its impact on weight, and unsurprisingly the weight loss was similar – and the tests it does, namely subcutaneous tissue, wouldn’t possibly show autophagy signals for just limited fasts. In no way does that study discount small fast autophagy, nor did it intend to.

It’s worth noting that someone really committed to autophagy should periodically have 48-72 hour fasts – yes, this is entirely healthy for most people⁷ – for deeper tissue autophagy. For instance quarterly.

As one final note, as a believer in alliesthesia and its ability to enhance our enjoyment of living, periods of going without food enhances the experience of the food you do eat. Too much of a good thing is very real, dulling the sense and ruining the enjoyment of the little things in life, and it’s good to periodically abstain.

Collagen

I regularly consume collagen supplements, usually in a tea to exit a fast.

I started on a whim after I developed pain in my Achilles tendon, which is a known possible side effect of statins as it can impair collagen repair. After supplementing with 5-10g of collagen daily, my tendon quickly returned to normal and have been great since. Which is a 100% worthless anecdote, and more likely it was just coincidence, and it’s possible my injury really was acute and would have repaired at the same rate regardless.

In any case, this was how I started taking collagen, from which I really looked into the evidence on either side.

Loads of medical influencers online dismiss collagen. Dr. Norton, since I previously mentioned him, is skeptical of collagen. He brings it up a lot, and it’s worth noting that he used to be very anti-collagen, but has moved to more of a skeptical middle grounds. Dr. Alex also dismisses collagen.

A frequent criticism of collagen – one that both of the aforementioned have made repeatedly – is that it’s a “poor quality” protein. Collagen is a “low quality” protein if your goal is leucine and anabolic effects, for which collagen is useless. For that you should be leaning on whey or other high-leucine sources in addition to collagen, serving different goals.

Collagen, in contrast, is glycine rich, and is an extremely high “quality” source of glycine, which has potent health benefits. Whey has glycine in small amounts as well, but if we’re ranking the quality of proteins by glycine – which is just as valid of a criteria for a different goal – then collagen is the super high quality protein source.

The Dr. Alex one – again, I enjoy and respect most of his takes – is particularly weak, leaning on various dismissals like that maybe they’re contaminated with heavy metals (which is the sort of “but what if?” rhetoric you find among anti-vax nonsense), he grossly exaggerates the price, and dismisses positive research because of who sponsored it⁸. I normally like his stuff, but that one was just bad all around, and if felt like he just repeated whatever anti-collagen claims he could find.

Dr. Alex repeats some other false claims that recur in collagen dismissals. For instance, he refers to some abstract amino pool from which our body builds things, and that collagen merely adds to those same amino acid stockpiles as the rest of our diet, and thus is fungible. This simply isn’t true.

Collagen ingestion yields unique di- and tripeptides that enter the bloodstream intact. For instance prolyl-hydroxyproline (Pro-Hyp) and other peptides. These are proven, significant stimulants of fibroblast activity that initiates tissue repair, conveniently also providing the building blocks for such repair to happen. These are not just free amino acids.

And all of this costs little. I got some giant bag of Organika stuff at Costco, and it has lasted for months. I have no doubt there are expensive variants, as with most consumer products you can pay many multiples for the same outcomes, but in no universe does collagen represent any particularly onerous cost in the supplement stack.

Is it going to make you young or give you the skin of a teen? No, of course it isn’t. Time is brutal and keeps on ticking. But it’s one of those cheap and so trivial things that I’m onboard.

Footnotes

1. Calling not eating constantly fasting is ridiculous, but that’s where we’re at. ↩

2. I used to lean on sucralose as my primary non-nutritive sweetener, but after some reasonably convincing RCTs showing some concerns (still a massive improvement over sucrose, but losing some of the advantage) I moved mostly to stevia drops (not the erythritol mixes), with occasional aspartame. Aspartame metabolizes to two amino acids and a tiny amount of methanol, which our bodies are constantly creating. ↩

3. Literally marketing, trying to push breakfast products. ↩

4. Breakfast clubs in schools are fantastic initiatives, especially for children who are food insecure. But for most adults breakfast truly is an optional meal. ↩

5. It should be noted that there is a third, no-man’s state where neither is particularly active. If you’re eating carbs and little to no protein, your glucose reserves are full so no AMPK, and there is no protein to fire mTOR, so both are idled. No building or harvesting, just lots of triglycerides filling your blood, getting stored away as fats. ↩

6. A number of observational studies have been done that show that even when people think they’re gorging during their eating window, their caloric intake has dropped measurably on the whole. ↩

7. Obviously if someone is underweight or unhealthy, then don’t. This sort of “there are exceptions” nonsense should not be necessary and is plainly obvious, but there will always by someone who demands it be clearly laid out. ↩

8. There is a common problem in scientific research that the only people willing to pay for large scale studies on topics are the same people who have a vested interest in a particular outcome. Like “big pharma” pays for most pharma research, collagen makers sponsor collagen research, etc. This is an inevitable reality of a system where these things cost money, and only a small number are incentivized to do the research. ↩