I see everyone raving about gelatin and collagen – and rightly so – they have amazing health benefits. However, no-one is addressing the fact that gelatin is actually used in tryptophan-depletion studies to lower serotonin (gelatin is derived from collagen: when collagen breaks down, it becomes gelatin). When I first discovered this fact it really concerned me that this very important aspect is ignored so I added it to my long list of topics to investigate.
I posted the above on Facebook last month as part of a fact-finding exercise and appreciate all the feedback and questions. Today I share some of the feedback and research and I’d love to hear from you what your experiences have been.
The health benefits of collagen
In case you’re new to collagen, Dr. Josh Axe provides an excellent overview of the health benefits of collagen
- Improves Health of Skin and Hair
- Reduces Joint Pains and Degeneration
- Helps Heal Leaky Gut
- Boosts Metabolism, Muscle Mass and Energy Output
- Strengthens Nails, Hair and Teeth
- Improves Liver Health
- Protects Cardiovascular Health
Gelatin is used in tryptophan depletion studies
Tryptophan-depletion studies have been done for years, as a way to study the relationship between low serotonin and depression. Often a tryptophan-deficient amino acid mixture is used for this purpose. More recently, collagen and gelatin are being used.
Collagen and gelatin are an excellent source of these amino acids: proline, glycine, glutamine and arginine, but they do not contain the amino acid tryptophan.
This paper, Pharmacokinetics of acute tryptophan depletion using a gelatin-based protein in male and female Wistar rats summarizes what we find in a number of studies that use gelatin for the purpose of lowering serotonin levels, in order to study the relationship between serotonin and behavior:
The essential amino acid tryptophan is the precursor of the neurotransmitter serotonin. By depleting the body of tryptophan, brain tryptophan and serotonin levels are temporarily reduced. In this paper, several experiments are described in which dose and treatment effects of acute tryptophan depletion (ATD) using a gelatin-based protein-carbohydrate mixture were studied in male and female Wistar rats.
My experience with collagen – flat and worried until I added tryptophan
When I recently injured my back and sprained my ankle, I decided to add collagen to speed up the healing and very quickly had to take a deeper dive into the topic because I noticed it affected my mood right away! I was using just one big scoop of collagen in a protein shake (pea protein) and yet I felt flat and slightly anxious within a day. It was the worried low-serotonin kind of anxiety in the early hours – something I haven’t felt in quite some time.
I wondered if it was due to the injury and inflammation my body was dealing with or if it was related to the effects of tryptophan depletion. I stopped the collagen and then added it back and had the same experience. I did this a few times and experienced similar feelings each time.
When I used tryptophan mid-afternoon and at bedtime I felt fine and was able to continue taking the collagen with no problems. I am prone to low serotonin – it was one of the root causes of my big anxiety issues in my late 30s – so I may be more affected than the average person.
Wondering if collagen causing mood issues and an increase in anxiety?
Here is feedback from someone who is wondering if collagen is causing her mood to dive:
I have wondered if it affects my mood so I haven’t been using it lately. Interested to see what other people say. I was using about a table spoon in a drink that I would sip on throughout the morning. My moods just take dives now and then. I have isolated gluten as a HUGE factor. I am forever wondering what else causes the dives and I began to wonder if collagen was causing problems so I haven’t used it in several months.
Stephanie feels moody when using collagen:
I have found that the days I take collagen that I’m moody. I’ve kept trying, but am always surprised by the reaction. I even mentioned it to my naturopath recently. Curious to see if there’s a connection.
Here is feedback from someone also reporting mood dives and feeling on edge (although as I pointed out to her the feeling on edge is very likely due to or partly due to the coffee):
I take collagen (grass-fed and grass-finished) in my coffee every morning. I’ve also had some mood dives consistently the last few months and feel more on edge. I’ve honestly never made the connection and actually thought it was hormones. Something to think about!
Melissa shared it affected her sleep:
As soon as I started taking gelatin daily I have had difficult falling asleep.
Katinka began having strange night time anxiety:
I did [Vital Proteins grass fed beef gelatin] for 2 weeks in bone broth. My nails grew like crazy, but at the same time I begun having strange night time anxiety: worry, obsessive, but not any of the other symptoms like depression and cravings. It is interesting to me because this was the only time I had anxiety at night since going gluten free.
Collagen caused a racing heart for Beverly:
Used to take Vital Proteins products. Was woken up several times in the night with racing heartbeat and out of breath. This went away when I stopped the collagen. I have symptoms of low serotonin but have not tried tryptophan
No noticeable problems
Many people shared that they didn’t notice any obvious mood issues so it’s clearly not a problem for everyone:
- Jaime: Interesting, I use it almost daily for protein at breakfast. I will pay attention better. No obvious problems now (used for 9 months).
- Angela: …I don’t think I have any side effects and I do have serotonin issues. I think I will have to do more research
- Courtney: I just started using collagen peptides but not every day. Maybe once or twice a week. I haven’t noticed any difference in mood but I also just started taking it a few weeks ago.
- Debra: I take 1bsp of Great Lakes Collagen Hydrosylate every day and take it to help heal my leaky gut….haven’t noticed any particular side-effects. I alternate it with the normal gelatin. I suffer from complex PTSD, anxiety and depression…I haven’t noticed any difference in that either
Jessica Drummond, nutritionist and physical therapist, and an expert on female pelvic pain and women’s health shared:
I use collagen regularly and I also eat quite a lot of meat and fish. For me both help me to feel very grounded and less anxious. I think of collagen as balancing for all of the muscle meat that we eat. I eat anywhere from 10-20 grams 4-5 days per week.
Feels anxious using gelatin, stop using it and anxiety is gone/less
Laura’s anxiety got worse within a few months of adding daily gelatin:
Wow, I never heard that gelatin can lower serotonin. I started using [Puritan’s Pride brand], 650mg, daily about 6 months ago to strengthen my nails. It’s worked very well for that. About a couple months ago my anxiety started to get worse again. My anxiety shows up as fear and worry mostly and not being able to quiet my mind. I had gotten it under control for almost 2 years now. I wonder if there is a connection. I’m going to stop taking the gelatin and see if my anxiety improves. I have not tried tryptophan, but I have found GABA helped quiet my mind and let me sleep better.
She decided to stop taking it to see if her anxiety symptoms would reduce and when I checked back with her she shared this:
I was surprised to find after about 2 weeks of stopping the gelatin, I began to feel more calm again and it’s been a lasting change. I still take zinc, vitamin b6 and lysine in the morning and GABA in the evening. This combination works well for me. I’m so grateful for all the information you share! Thank you!
Toni experienced something similar:
I’ve been using Organic collagen for about 8 months now… love the hair and skin results. My tummy felt better at first but not currently. My anxiety and panic attacks are off the charts: panic attacks, heart racing, sweating, brain fog. I want to escape -like fight or flight. Definately obsessing and fears. Memory difficulty. I have an upcoming GI appointment to check for Candida /SIBO… but I had no idea this could add to my anxiety. I’ll be looking forward to more information, Seriously.
And a few weeks after stopping the collagen she shared this:
I stopped using the collagen. Since then, my anxiety and panic are decreased by less than half. Mild in comparison. I’m definately taking a long break.
Keep in mind I’m not suggesting we should not be using collagen – just that if it seems to lower serotonin and increase anxiety/depression doing a trial with tryptophan may be the solution (more on that and some other possible causes of anxiety below).
When used with tryptophan – no mood issues
Karen uses collagen and tryptophan at night:
I use collagen every day. But hey, I also take L-tryptophan every night for anxiety. It runs in the family and a small amount of Tyrptophan at night helps resolve mine. No clue there was a connection
Maxine uses it every morning and takes 1 tryptophan before bed and reports no mood issues
I take it [Great Lakes gelatin and Vital Choice collagen] every morning in my tea and at night in my bone broth for my skin and joints and I take one tryptophan before bed. The tryptophan with GABA before bed is for better sleep. No mood issues.
Used ‘therapeutically’ to lower serotonin
Misty reports using it ‘therapeutically’ to lower her high serotonin levels. This application is new to me and I find it quite fascinating:
I use it to reduce tryptophan because I have a tendency toward high serotonin. I have suffered my entire life with ADD, tics as a child, grinding teeth, general anxiety, lack of motivation and later, IBS. In my quest to maximize my health, I finally came to these web pages for help. In my 53 years I’ve never been as calm as I am now. If I’m not careful, I can get a bout of IBS (not food related and trust me, from GAPS to AIP, nothing really affects me). I reduce tryptophan and I’m balanced. It seems contrary but it works for me and so many others
She links to these articles Tryptophan, Sleep, and Depression and The Sadder Side of Serotonin which both refer to the work of Ray Peat who I recently discovered is very much against the use of tryptophan.
I agree with the premise of too much serotonin causing issues (often the same symptoms we see with serotonin that is too low) but not the general message that tryptophan supplements and foods high in tryptophan are harmful and should be avoided by everyone. Based on the clinical results myself and other practitioners see boosting low serotonin with tryptophan and/or 5-HTP -and the wonderful results they experience – in my opinion, this is really all about biochemical individuality.
I decided to share this story here, even with the controversial tryptophan articles, because it illustrates that it is highly likely that the collagen is lowering her serotonin levels and making her feel better. I’ll tackle the above negative articles about serotonin and tryptophan in a separate blog post.
Why are some people adversely impacted by acute tryptophan depletion/ATD while others are not?
UPDATE: Dec 22, 2017. This section adds additional evidence or possibly some theories for why some people are adversely impacted when consuming collagen, while others are not impacted mood-wise – all related to the lowering of serotonin levels. These are called ATD or acute tryptophan depletion studies.
This paper: The effect of raising and lowering tryptophan levels on human mood and social behavior explains that effects of ATD can vary based on susceptibility of the study participants to clinical depression:
Acute tryptophan depletion (ATD) studies indicate that low serotonin can lower mood and also increase aggression, although results vary somewhat between studies with similar participants. Lowering of mood after ATD is related to the susceptibility of the study participants to clinical depression, and some participants show no effect on mood.
In healthy individuals, there is little or no lowering of mood, although results can be quite variable between studies, with some lowering of mood seen more often in women than in men.
The author reports the following variable responses:
In healthy participants with a family history of depression, there is a lowering of mood although mood remains within the normal range of mood.
In newly recovered depressed patients on antidepressants that act on the serotonergic system, 50 per cent or more of the patients show a temporary reappearance of the depressed mood they experienced before recovery.
In recovered depressed patients off antidepressants, only a small percentage of the patients show a marked lowering of mood.
In recovered depressed on noradrenergic antidepressants, there is no lowering of mood.
The results of the ATD studies suggest that lowering serotonin synthesis can lower mood in some circumstances, and that the magnitude of the effect tends to be greater in people with a greater susceptibility for depression.
Other studies report on these groups of people that were adversely affected with a lowered mood after ATD:
OCD / obsessive compulsive disorder: Patients with OCD experienced a decrease in control and an increase in interfering thoughts after acute tryptophan depletion. There was no effect on anxiety in this group.
Genetic polymorphisms: A number of papers show some genetic polymorphisms make some individuals vulnerable to increased depression after acute tryptophan depletion, such as MAOA and 5-HTTLPR (the serotonin transporter gene). In one 5-HTTLPR polymorphism study differences were seen between men and women: healthy men became more impulsive, whereas healthy women showed a mood reduction after ATD. Keep in mind that having a polymorphism doesn’t mean there will always be an issue, instead, it means there may be a predisposition.
Comorbidity between depression and tobacco use may reflect self-medication of serotonergically mediated mood dysregulation [and acute tryptophan depletion or ATD] increased self-ratings of depressed mood [in certain smokers].
Although this study was looking at the role of nicotinic receptors in disordered mood and the self-medication of mood by smoking, we may be able to extrapolate this for our purposes because it was this one subset of smokers who were more depressed after tryptophan depletion. Could it be that smokers or even former smokers are more likely see increased depression after consuming collagen because it contains no tryptophan? Or is it that smokers tend to be drawn to smoking because they are prone to low serotonin?
Women polydrug ecstasy users appear to be more susceptible than men to the effects of lowered serotonin levels [when they] received a tryptophan-deficient amino acid mixture and a control amino acid mixture containing tryptophan, at least 1 week apart.
The women who were impacted – with a lowering of their mood – used a tryptophan-deficient amino acid mixture and not collagen. The authors suggest this could be due to the drug-use causing progressive damage of serotonin neurons. Could this also happen with collagen consumption in current and possibly prior drug users? What about users of other street drugs or even medications that may also damage serotonin neurons?
Interestingly, in a study looking at five chronic fatigue/CFS patients, none of them showed any significant differences in fatigue, depression and concentration when subjected to acute tryptophan depletion /ATD. Was this group of patients too small or were none of them susceptible to low serotonin?
This is just a small selection of studies looking at the effects of acute tryptophan depletion or ATD but they give us much to think about when it comes to considering the varied effects we are seeing when individuals consume collagen.
If collagen affects you adversely and makes you feel more depressed, more anxious and experience worse sleep, can you relate to any of the above scenarios?
More questions and looking for your feedback
As you can see we have very different experiences but there are enough unanswered questions we need to be asking:
- Are the negative effects because of low serotonin? If yes, are some of us more susceptible to the serotonin-lowering effects than others and should we stop using collagen despite all the health benefits?
- And should we be assessing for low serotonin levels before using collagen or gelatin, and supplementing with tryptophan when it is low (more on this below)? There is one company that has added tryptophan to their collagen – is this a good idea?
- Or are the negative effects some people experience due to glutamates, arginine, histamine, because of quality issues and glyphosate levels, an increase in oxalates or something else such as not eating enough animal protein?
I’ll address the above questions and share some additional research and feedback from collagen experts in part 2 of this article.
Until then, if you have observed a mood dip or increase in anxiety since using collagen or gelatin, I would suggest you stop using collagen/gelatin and see how you feel, then add it back and see how you feel. If you do see a correlation, do the low serotonin questionnaire and a trial of tryptophan (after checking the precautions) to see if this improves your mood when using collagen/gelatin. I recently blogged about tryptophan here (brand is important).
I would love your feedback. Do you use gelatin or collagen regularly i.e. daily or weekly? And why do you use it? How do you use it and what benefits do you notice?
Have you noticed any worsening of mood or an increase in anxiety or any of the other low serotonin symptoms? Do you take tryptophan to offset the fact that gelatin or collagen doesn’t contain any tryptophan?
Have you done the off/on test with collagen/gelatin and what was the outcome?
I’d love your feedback in the comments. Be sure to share what you’re using (collagen or gelatin and the brand), how much, how often you consume it, what you take it with, how much caffeine you consume, how much protein you consume on a daily basis and what kind of protein, and how you react to home made bone broth. If you’re comfortable with sharing how you score on the low serotonin questionnaire (now or in the past i.e. are you prone to low serotonin) and if you’re using a SSRI (or have in the recent past), this may help us piece the puzzle together.