As the control center for everything happening in our bodies, eating for brain health should be a top priority all year long. In wintertime especially, we need our brains functioning at maximum efficacy to protect mental health. Serotonin is one particular neurotransmitter (signaling chemical) we depend on heavily for our health. While serotonin’s key functions range from digestion to sleep, it is most famous for its effect on mood. Serotonin is known as the “happy” chemical, as dysregulation in its abundance or activity is related to symptoms of depression, aggression, anxiety, impulsivity, and other mood disorders [1].

Because serotonin production and signaling depend on the availability and action of many other nutrients, it is possible for a person’s diet to disrupt healthy serotonin function. Read on to see if there are any nutrients you might be missing, or could use a little more of to keep serotonin signaling running smoothly in your body.

High Protein Foods, Tryptophan, and 5-HTP

Tryptophan is an essential amino acid, which means humans need it from our diet because our bodies don’t synthesize it. Serotonin is synthesized from tryptophan in both the gut and the brain. To make serotonin, the enzyme tryptophan hydroxylase converts tryptophan to 5-hydroxytryptophan (5-HTP), which is then decarboxylated to produce serotonin. Although tryptophan hydroxylase is the rate-limiting enzyme in the synthesis of serotonin, it is not saturated in normal circumstances, which means serotonin production is highly sensitive to changes in dietary tryptophan levels [2].

High-protein foods are a great source of tryptophan; specifically, poultry, eggs, fish, and dairy products. If you do not eat many (or any) animal products, tryptophan can also be found in tofu, peanuts, and other plant-based protein sources. If you are concerned that your diet may be lacking in tryptophan, L-tryptophan can be supplemented. A superior choice for mood, however, is likely to be 5-HTP supplements. 5-HTP is the direct precursor to serotonin and can cross the blood-brain barrier, unlike L-tryptophan [2]. Studies have shown that 5-HTP exhibits more pronounced antidepressant activities than L-tryptophan supplementation [3]. 

If you choose to supplement with either of these nutrients, try taking them before bed. Both L-tryptophan and 5-HTP are not only precursors for serotonin, but also melatonin production. Melatonin is a chemical that helps us fall and stay asleep at night. 

Vitamin D

Vitamin D is a key regulator of tryptophan hydroxylase, the enzyme required to transform tryptophan into serotonin [1]. Vitamin D can only be made in our bodies when we are getting daily, direct exposure to the sun (without sunscreen). As the days get shorter, it’s harder to carve out time in busy schedules to get out in the sun. If it’s too cold to leave any skin exposed, your body can’t make vitamin D. Therefore, some people are more likely to feel depressed in the winter due to vitamin D deficiency. 

Although some foods (such as milk and orange juice) are fortified with vitamin D, it’s typically not enough to make up for a lack of sun. There are very few natural food sources of vitamin D. Due to this factor, it has been estimated that around 70% of Americans are vitamin D insufficient (up to 91% of pregnant women and 67% of children) [1]. Vitamin insufficiencies and deficiencies in most people can be mediated with a daily supplement, but multivitamins containing vitamin D are still not enough to meet the needs of some individuals. For example, one study reported that 50% of women taking prenatal vitamins (and their neonatal offspring) were still vitamin D insufficient [1]. If you are concerned with your vitamin D levels, your doctor can do a simple blood test to determine a safe dose for supplementation without toxicity.

L-Methylfolate

L-Methylfolate has received a lot of positive attention in the last few years, and has been prescribed to many as the only active ingredient in the medical food, “Deplin”. L-Methylfolate is the activated form of the B-vitamin, folate, and it participates in methylation throughout the body. One of the many, many purposes methylation serves in the body is the synthesis and metabolism of neurotransmitters such as serotonin. 

While folate can be found naturally in many foods, it is not very bioavailable. This means that the proportion of active folate that makes it all the way to your circulation is very small compared to the amounts that were measurable in your food before you ate it. Due to this factor, and widespread folate insufficiencies, many commonly consumed foods (rice, pasta, cereal, etc.) are fortified with folic acid (a synthetic form of folate). Folic acid is a more bioavailable form of folate for some people. However, up to half of the world’s population (and likely about 70% of those suffering from depressive disorders) do not process folic acid efficiently due to genetic polymorphisms [4]. If this is the case for you, you may experience symptoms of folate deficiency even when consuming high levels of dietary folate. 

Supplementary L-methylfolate can be the solution to this biochemical problem. L-methylfolate is the activated form of folate and is highly bioavailable. It requires no further processing in the body, so it can be used as soon as it is absorbed, by everyone, regardless of genetics. With MethylPro, you can supplement high-quality, pure L-methylfolate in varying doses (comparable to those in Deplin) without a prescription.

SAMe

S-adenosyl-L-methionine, or SAMe, like L-methylfolate, is a methyl donor and cofactor in the neurotransmitter synthesis pathway. Although SAMe is produced naturally by every cell of the body and brain, deficiency has been reported in patients with inherited defects in folate and methionine metabolism (such as MTHFR mutations) as well as in common diseases such as depressive disorders, Alzheimer’s Dementia, Parkinson’s Disease, and HIV [5].

Animal studies show that supplementary SAMe can increase serotonin levels, but not in the same way as SSRI medications. While SSRIs make the activity of each neurotransmitter last longer by blocking its reuptake, SAMe appears to actually help to build more neurotransmitters [6]. Because of this mechanism, if you are already taking SSRI medication, do not start taking SAMe without discussing it with your psychiatrist or doctor. On the other hand, if you fall in the 50% of people who are “treatment-resistant” or don’t feel a response to antidepressant medication, there may be even more reason to give SAMe a try [6]. 

Probiotics

Did you know that 90-95% of the serotonin in your body is made and used by the gut? It gives new meaning to the old saying “gut feeling” doesn’t it? And of course, a huge part of a healthy, functioning gut is the health of the microbial community living within it. 

There have been numerous studies demonstrating a relationship between prebiotics, probiotics, and mental health. For example, the abundance of Bifidobacterium and Lactobacillus microbes are typically lower in patients with depressive disorders [7]. But, just as there are many beneficial strains of probiotics, there are also many different mechanisms of action explaining how and why this relationship exists. For a few specific strains, there seems to be a direct association with neurotransmitter production, including serotonin. Some strains, such as Lactobacillus brevis and Lactobacillus plantarum (both of which can be found in Metabolic Maintenance’s BioMaintenance® Shelf-Stable Probiotic) actually produce GABA and serotonin which is released into the host [7]. Indigenous spore-forming bacteria have also been found to promote endogenous serotonin production in their host’s gut cells [8]. These “indigenous” strains are not probiotic species that can be supplemented, but they can be nurtured and cultivated through diet and prebiotic supplementation. Prebiotics are essentially food for probiotics. Fiber and oligosaccharides encourage the growth and multiplication of beneficial microbes living in the gut while discouraging the survival of pathogenic bacteria.

References

  1. Patrick, Rhonda P., and Bruce N. Ames. “Vitamin D and the omega‐3 fatty acids control serotonin synthesis and action, part 2: Relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior.” The FASEB Journal 29.6 (2015): 2207-2222.
  2. Nichols, Charles D., and Elaine Sanders-Bush. “Serotonin.” (2003): 245-248.
  3. Lake, James. “L-Tryptophan and 5-Hydroxytryptophan in Mental Health Care”. Psychology Today. Sept. 29, 2017. https://www.psychologytoday.com/us/blog/integrative-mental-health-care/201709/l-tryptophan-and-5-hydroxytryptophan-in-mental-health#:~:text=The%20amino%20acids%205%2Dhydroxytryptophan,a%20more%20pronounced%20antidepressant%20effect.
  4. Shelton RC, Sloan Manning J, Barrentine LW, Tipa EV. Assessing Effects of l-Methylfolate in Depression Management: Results of a Real-World Patient Experience Trial. Prim Care Companion CNS Disord. 2013;15(4):PCC.13m01520. doi:10.4088/PCC.13m01520
  5. Sharma, Anup, et al. “S-Adenosylmethionine (SAMe) for neuropsychiatric disorders: a clinician-oriented review of research.” The Journal of clinical psychiatry 78.6 (2017): e656.
  6. Estroff Marano, Hara. “The SAM-e Story”. Psychology Today. Last reviewed on June 9, 2016. https://www.psychologytoday.com/us/articles/200203/the-sam-e-story
  7. Cheng, Li-Hao, et al. “Psychobiotics in mental health, neurodegenerative and neurodevelopmental disorders.” journal of food and drug analysis 27.3 (2019): 632-648.
  8. Yano, Jessica M., et al. “Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis.” Cell 161.2 (2015): 264-276.