How Not to Follow Bad Health Advice and The Depressing Issue with the Collagen Supplementation Fad

There's always a whole lot of noise out there when it comes to health trends in the blogosphere. But it's often easy to detect a new signal because I'll get asked about the same thing by three different people within a short period of time.

"What's your take on colonics for detox?" asks a patient, my accountant and an Uber driver.

Or zinc to prevent infection. Or peptides for autoimmunity.

The problem with these types of questions is that they're focused on a specific tool rather than going through a structured process. Spoiler alert: there's no specific tool that will help you resolve complex health issues or keep you healthy as you go through life in any sort of reliable way.

We need to approach health differently. Systematically, using a process.

If you were renovating a dilapidated house, you wouldn't start by buying a specific set of shingles or a new light fixture based on a Facebook ad. Imagine buying new windows because of all the amazing features that were touted without determining if they were the right size for your house? Or if you even needed new windows in the first place?

First, you would assess the damage, determine the scope of the job and go through a process, in a logical order. Selecting specific tools would be less important than the sequencing, thoroughness, and appropriateness of the process for undertaking the work.

But when it comes to health, the internet primarily deals in selling people tools and convincing them that these tools stand between you and your health goals.

Lately, what I get asked most often is about whether everyone and their great aunt needs to supplement with collagen. The message seems to be that it's good for skin, hair, the gut, and the bones. It'll help you re-build yourself! What's not to like?! Surely, it's a case of the more the better!

What we've learned about collagen from the twisted world of anti-depressant research

The serotonin hypothesis of depression was officially debunked earlier this year with a systematic mega-review that showed no association between serotonin levels or serotonin genes and depression.^[1] It did however show that anti-depressant use is associated with lower serotonin, something I've seen consistently on my patients' labs. In a nefariously ironic twist, serotonin depletion due to SSRI use is the primary reason that these and other anti-depressants are so difficult to come off of, because they cause serotonin deficiency.

However, because the serotonin hypothesis of depression was the primary rationale for selling billions of dollars of drugs that can correct this Pharma-invented problem (i.e., low serotonin as the main cause of depression), lots of research has been done on the effect of depleting serotonin in people, primarily by depleting tryptophan from which serotonin is made, to see if this makes them depressed. And then using this engineered depletion as a rationale, not to restore their tryptophan levels or raise awareness of how crucial this amino acid is to mood and brain health as logic and humanity would indicate, but to recommend anti-depressants.

I find this to be truly twisted.

So, what's this have to do with collagen supplementation?

Well, when it comes to acutely depleting someone's tryptophan to make them depressed, the tried and true method used in research is to give them a protein supplement that contains all of the essential amino acids except tryptophan. By doing this, you're essentially lowering the relative amount of tryptophan in the body compared to the other amino acids. And because of the way absorption and transporters work in the body, which often involves competition, less relative tryptophan translates to less total tryptophan being absorbed through the gut and transported across the blood brain barrier to be available for making serotonin in the brain.

The problem was that this lab derived concoction, while very effective for lowering tryptophan, tended to cause tummy upset and other side-effects.

But collagen and gelatin are actually natural versions of this. Collagen contains all of the essential amino building blocks of proteins except tryptophan, which is only present in negligible amounts. This is important. Tryptophan is present in all proteins in our body except collagen and is the rate-limiting amino acid for protein production. What this means is that it's actually the amino acid that we have in the smallest quantity so when it's low, we can't make all of the different proteins and enzymes we need and we start having to make trade-offs.

Here's how one study describes using collagen to deplete tryptophan in order to cause serotonin deficiency in the brain:

Acute Tryptophan Depletion (ATD) is a widely applied dietary method used to lower plasma Trp and thereby the amount of Trp available for central 5-HT synthesis (Carpenter et al., 1998; Mendelsohn et al., 2009). The most commonly administered application of ATD is by intake of a mixture containing all 15 essential amino acids (AAs) except for Trp, which has been shown to elicit gastro-intestinal side effects. An alternative and potentially more tolerable approach involves ingestion of a gelatin-based collagen peptide (CP) mixture that is naturally lacking Trp (CP Trp), which is contrasted by using a CP mixture supplemented with Trp (CP+ Trp).”^[2]

So because collagen contains all essential amino acids except tryptophan, collagen supplementation is a well-studied and effective way of lowering tryptophan levels in people. Back in 2004, a study demonstrated that using a "novel" mixture, they were able to effectively induce acute tryptophan deficiency. The novel collagen protein mixture? It was simply powdered gelatin mixed with water.^[3]

Literally dozens of studies have used this design, giving a collagen drink, in an attempt to cause depressive symptoms by lowering serotonin in the brain.^[1]

So maybe this isn't the most intelligent health & beauty hack ever conceived.

How could you figure this out without being aware of these studies?

It's impossible to keep up with the rate of published research, even if you have lots of letters after your name and lots of time on your hands, let alone if you're simply a regular person doing the best you can to get and stay well.

So how could you figure out that daily scoops of collagen may come with risks of tryptophan depletion if you're unaware of these studies? Well, the most important thing is to look at the context of any health practice or supplement and the context I find without fail to provide the most helpful lens as a starting point for these types of questions is that of evolutionary biology.

So then you can ask: when would pre-agricultural people have been consuming lots of collagen in isolation from it's source? The answer is, I don't think they ever did. They did eat animals head to tail and they did make things like bone broth that is high in gelatin and collagen. In many places throughout the world in with diverse habitats and dietary patterns, pre-agricultural people generally consumed more collagen than modern people who tend to favor eating muscle meats over collagen rich joints and skin or may be avoiding animal products all together.

But they did not separate this collagen out, as far as I'm aware, and consume it on its own.

So that, coupled with the robust research on how collagen supplementation has been used to sell anti-depressants, leads me to believe that it's unlikely helpful for "everyone" to be doing this or that "it's good" in some sort of blanket sense, or that without further information about your specific problem, that this is something you should be doing.

So my advice, generally speaking, would be to maximize collagen rich dietary sources, which naturally contain some tryptophan in, as well as lots of other stuff that neither of us has even heard of. That's the beauty of the evolutionary context, you don't have to no everything.

References

1. Moncrieff, Joanna, Ruth E. Cooper, Tom Stockmann, Simone Amendola, Michael P. Hengartner, and Mark A. Horowitz. “The Serotonin Theory of Depression: A Systematic Umbrella Review of the Evidence.” Molecular Psychiatry, July 20, 2022. https://doi.org/10.1038/s41380-022-01661-0.
2. Stenbæk, D. S., H. S. Einarsdottir, T. Goregliad-Fjaellingsdal, G. M. Knudsen, V. G. Frokjaer, and S. G. Hasselbalch. “Evaluation of Acute Tryptophan Depletion and Sham Depletion with a Gelatin-Based Collagen Peptide Protein Mixture.” European Neuropsychopharmacology 26, no. 1 (January 1, 2016): 147–49. https://doi.org/10.1016/j.euroneuro.2015.11.010.
3. Evers, E. A. T., D. E. Tillie, F. M. van der Veen, C. K. Lieben, J. Jolles, N. E. P. Deutz, and J. A. J. Schmitt. “Effects of a Novel Method of Acute Tryptophan Depletion on Plasma Tryptophan and Cognitive Performance in Healthy Volunteers.” Psychopharmacology 177, no. 1 (December 1, 2004): 217–23. https://doi.org/10.1007/s00213-004-1933-4.