Boosting Serotonin with Food and Supplements: What you Need to Know
- How the body makes serotonin
- High-protein meals may lower serotonin
- The role of insulin in serotonin production
- Serotonin boosting supplements
- Serotonin supplements and their side effects
- Serotonin boosting supplements with potential efficacy
- Closing thoughts on serotonin supplements
How the body makes serotoninThe body uses the amino acid L-tryptophan as the precursor to serotonin. The interesting thing about L-tryptophan is that it does a poor job of competing with other amino acids for uptake into the brain, where it is then ultimately used to make serotonin.
High-protein meals may lower serotoninWe would assume that high protein meals, that contain greater amounts of tryptophan, would cause the greatest spike in serotonin levels, but studies show just the opposite is true. Eating a portion of turkey causes levels of tryptophan in the blood to rise, but tryptophan circulating in the blood isn’t usable by the brain to make serotonin. Why? Early analysis in rat models revealed that it’s not the plasma tryptophan that is the issue for serotonin production, the issue is the ratio of tryptophan to other “competitive” amino acids fighting for space in the brain. Studies in rats showed that eating a meal of carbohydrates and fat, but no protein, increased serotonin, whereas a protein rich meal decreased serotonin. Interestingly, when the experiment was performed in humans, the meal of fat and carbs did not increase serum tryptophan, but it did increase serotonin in the brain.
The role of insulin in serotonin productionWhy do high carb meals boost serotonin? The mechanism seems to be insulin. Carbohydrate rich meals were shown to increase tryptophan levels in the brain (not in the blood), because levels of most other competing amino acids are lowered when our blood sugar spikes. Like most amino acids, tryptophan levels in the blood go down with insulin spikes, but they compensate by binding to other molecules, which makes them usable by the brain to make serotonin. In essence, tryptophan does a poor job of competing against other amino acids for uptake in the brain, and it needs a “clear playing field” to get to the brain to make serotonin. Insulin is what clears the playing field.
Insulin causes nonesterified fatty acid molecules to dissociate from albumin and to enter adipocytes. This dissociation increases the protein’s capacity to bind circulating tryptophan; hence, whatever reduction insulin causes in free plasma tryptophan levels is compensated for by a rise in the tryptophan bound to albumin, yielding no net change in total plasma tryptophan levels in humans.So, the lesson here is amino acids compete for binding sites in the brain. Tryptophan does a bad job of competing against other amino acids, and therefore uses insulin to get in the brain where it needs to be to make our feel good friend serotonin. When plasma levels of other amino acids fall, the ability of tryptophan to get into the brain increases.
Serotonin boosting supplementsAs it pertains to food, we’ve learned that foods that are highest in tryptophan are not necessarily the ones that will increase uptake of serotonin to the brain and ultimately serotonin levels. Perhaps somewhat counterintuitively, carbohydrate rich meals actually help the body make serotonin. So, what about dietary supplements? There seems to be a never ending list of “nootropic” supplements that make grand claims about boosting mood and cognitive ability. None of these supplements are FDA approved, but they can have an impact on neurotransmitter levels in the brain. Which of these supplements increase serotonin? Let’s dig in and find out.
Serotonin supplements and their side effects
|5-HTP||Potential for too much||Can have very unpleasant side effects depending on dosage, may affect other neurotransmitters|
|SAM-e||Too much||May interact with other drugs or supplements aiming to also boost serotonin|
|Saint John's Wort||Too much||Side effects, plus potential to dangerously increase serotonin if taken with other serotonin boosters|
|Low-dose Vitamin B6||Adequate||Low levels of B6 associated with depression, but high levels associated with nerve damage|
|Vitamin D||Adequate||Vitamin D deficiency is linked to low levels of serotonin and depression|
|Omega-3 fatty acids||Adequate||DHA may promote serotonin receptor activity, while EPA promotes serotonin release; not all see a positive effect|
|Theanine||Adequate||Linked to serotonin and dopamine levels, but unsure how L-theanine induces effect|
Serotonin boosting supplements we don’t likeWe begin the conversation with 5-HTP, as that is the supplement most would mention when talk of boosting serotonin comes up. 5-HTP (potential for too much serotonin)Just as there are multiple steps in converting folate into methylfolate, the form of folate the body can readily use, tryptophan undergoes a conversion process on its way to becoming serotonin. As part of that process, L-tryptophan becomes 5-HTP. 5-HTP is especially popular as a serotonin boosting supplement, as there are safety concerns surrounding taking L-tryptophan as a supplement directly, and many studies looking at L-tryptophan supplementation show only middling results, presumably because amino acid balancing was not taken into account. 1 And, in light of Wurtman’s work, I find the concept of a tryptophan supplement odd to begin with as it’s not the serum tryptophan, but the neutralization of more cognitively bioavailable amino acids that seems to dictate serotonin levels.
5-HTP Side EffectsThe scientific consensus has stark warnings on the use of both L-tryptophan and 5-HTP, see this strongly worded article for an example. 2 The authors summarize the issue perfectly in their conclusion so I’ll just quote verbatim (emphasis mine):
So, bottom line is that an amino acid precursor, like 5-HTP, may increase serotonin, but it does so at the expense of your other neurotransmitters. It’s an interesting paper, and I found this image particularly useful in understanding the neurotransmitter-amino acid balance, and some of the severe issues that can arise from 5-HTP supplementation, namely depletion of dopamine: Image from 5-HTP efficacy and contraindications, Hinz M et al, 2012. Interestingly, the authors talk about an approach to achieve a balanced administration of 5-HTP using a technique called monoamine transporter optimization (MTO), which measures and balances serotonin and dopamine, giving optimized individual dosing targets. I’ll admit this is a new technique to me and so I’m not sure how widely available it is as a test. Thing to remember here is that neurotransmitters, and the amino acids that make them, all act in concert. Flooding the system with one won’t give you the feeling you’re looking for, at least not for long.
5-HTP in the treatment of depression has languished for years. Intuitively, the potential is extraordinary, but from a practical level efficacy is no better than placebo. In review of the science, effective integration of 5-HTP into a patient management plan is much more complicated than simply giving some 5-HTP in order to have more serotonin throughout the system.
Administering serotonin or dopamine amino acid precursors should never involve administration of only one amino acid. Improperly balanced amino acid precursors are associated with decreased efficacy, increased side effects, and depletion of the nondominant system.
What is considered a low dose of vitamin B6 is it better to take it at night or in the day? Can I take 5-htp with L- theanine at night to help me sleep better or should I take Gaba with my L-theanine for better sleep?
As a non-academic vegetarian looking to safely and naturally balance my serotonin levels, I found your article very interesting, and accessible. As for the bottom line on safe serotonin supplements, my perhaps mis-informed question, is this: Of your 4 recommended supplements at the end of the article, is one to choose only one, or all or a combination?
I found this article very helpful and considering I just started p5p for insomnia and high estrogen. It’s interesting that you didn’t mention estrogen considering estrogen diverts tryptophan away from serotonin metabolism and toward the kynurenine pathway. But, I can’t claim finding this research on my own as I had a Dr tell me this.
Flooding the body with any nutrient or neurotransmitter will cause down regulation of the receptors as a protection mechanism. A negative feedback loop can also cause less natural production of the neurotransmitter or hormone