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BRAIN GAINS Part One: Serotonin

Brandie Mabee
BScPhm, RPh

Neurotransmitters are the biochemical messengers responsible for our many mental functions, such as focus, memory, mood, motivation, relaxation, socializing, and cognition. I became intrigued by the quest to “hack” said messengers almost as soon as I began learning about them in pharmacy school. As my foray into the sport of bodybuilding progressed, I recognized the crucial role my mental function was playing in the gym and the kitchen. Our bodies have limitless potential; it’s most often our weak mental game that holds our physiques back. I’m not sure why nootropics aren’t as prominent as protein powder and BCAAs in the supplement market, but that’s starting to change, so it’s high time that I share my knowledge with the MUSCLE INSIDER audience and get you educated on the basics before nootropics become the new craze.

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Nootropics, also known as “smart drugs,” are a class of supplements that enhance cognitive functions by boosting our neurotransmitter levels. The same way nitrous oxide precursors such as citrulline can assist in NO production to stimulate vasodilation and improve blood flow to our muscles, nootropics are often precursors to neurochemicals with equally desirable effects in the cognitive arena.

Serotonin is the brain chemical most responsible for our mood. A person with optimal serotonin levels is happy, calm, and able to fall asleep without any issues. Serotonin is mainly found in the brain and in the gastrointestinal (GI) tract. In fact, up to 90 percent of your serotonin is found in your GI tract. Serotonin has important implications in gastrointestinal function and autoimmune diseases, but for the purpose of this article we will focus solely on its cognitive role.

Low serotonin levels are associated with depression, anxiety, fear, insomnia, fatigue, and my personal favourite, apathy. It’s kinda hard to push yourself in the gym, classroom, and workplace when you literally just don’t care. Another interesting area of research is the connection between low serotonin and eating disorders. In fact, Prozac (an antidepressant with a primary mechanism of action of increasing serotonin’s effects) is Health Canada-approved for treatment of bulimia and binge-eating disorder.

The most natural ways of boosting serotonin are light therapy and carbohydrate intake. Research suggests that serotonin turnover declines in the winter, when daylight is shortest. This explains the infamous seasonal depression that hits some of us around the holidays. With respect to diet, carbohydrates result in a relative increase in brain levels of an amino acid called tryptophan, a serotonin precursor. This helps explain why fitness competitors who get down to very low carbohydrate intake experience low mood, sleep disturbance, and anxiety as they get closer to contest day. Because serotonin can make you sleepy, this also helps to explain the “food coma” that takes place shortly after a big carb binge.

Are there any magic pills to pump up your “happy chemical”? Maybe. Unfortunately, we can’t measure brain serotonin levels before and after supplementation, so the truth is, we don’t know if anything truly boosts brain serotonin. If there’s one thing evidence-based medicine has established, it’s that just because something intuitively makes sense, that doesn’t mean it’s what actually happens inside our bodies. What we can do is look at the subjectively reported effects of these compounds on health conditions that are correlated with low serotonin levels, such as depression and anxiety. 

  • St. John’s Wort
    • St. John’s wort (or SJW) is one of the most well-studied natural products ever. The bulk of the research is for the treatment of depression, but it has also been studied for anxiety, OCD, social phobia, menopausal symptoms, PMS, and seasonal affective disorder.
    • I recommend it to patients who aren’t willing to take pharmaceutical selective serotonin reuptake inhibitors (SSRIs), because it has reasonable evidence of benefit, and a similar mechanism of action to the SSRIs. Much like the pharmaceuticals, it takes about four to six weeks to improve symptoms.
    • My concern with SJW supplements (and all non-pharmaceutical products) is that their quality and potency isn’t as stringently controlled as the products that require a prescription. I’ve read assay reports (de los Reyes GC, Koda RT 2002 is one example) that have observed variability in key active compounds ranging from 50 percent to 135 percent of the stated amount on the label. I encourage the reader to seek out brands with transparent manufacturing protocols and third-party quality testing.
    • The most robust evidence-based dosage of SJW is 300 milligrams standardized to 0.3 percent hypericin, taken three times daily for at least six weeks. SJW ramps up liver enzymes responsible for drug metabolism, so check with your health care professional for interactions if you take other medications.
  • 5-HTP
    • 5-HTP is a precursor to serotonin. Its research resume isn’t nearly as impressive as SJW, but it has some preliminary evidence of benefit in depression and has fared relatively well in head-to-head studies against pharmaceutical serotonin boosters. For depression, the doses range between 150 and 800 milligrams per day. 5-HTP is also a popular sleep supplement, with some evidence suggesting it reduces time required to fall asleep; for this reason, I recommend starting on the low end of the dose range and taking it in the evening.
  • L-tryptophan
    • Another serotonin precursor, L-tryptophan is a popular product amongst insomniacs. Overall, it isn’t well-studied in disorders of serotonin deficiency, so it would be one of my last choices if you’re looking to boost your serotonin. This is a good example of a therapy that intuitively “makes sense,” but doesn’t have the concrete evidence behind it.
    • In depression, 300 milligrams daily has been used; for insomnia, 1000 milligrams 30 minutes before bedtime. The most common side effects are GI-related (stomach pain, nausea, diarrhea, etc.) so I recommend taking it when there’s food in your stomach.
  • SAM-e
    • SAM-e has been formally studied for depression and other serotonin-related mood disorders as far back as the 1970s. Unlike 5-HTP and L-tryptophan, it’s not a serotonin precursor; its antidepressant action is probably due to its ability to increase serotonin turnover. The average regimen is 800 milligrams twice daily for up to eight weeks. Like L-tryptophan, the bulk of its side effects are GI-related, so it should be taken after eating.

A few final points: seek care from regulated health care professionals who are familiar with you and your medical history, and include them in your decisions to try nonprescription products. Educate yourself by using credible, unbiased resources, and always ask yourself this: “What does the person who is informing me have to gain or lose if I follow their advice?” When trying natural health supplements, seek quality products with reasonable evidence to support benefits, and use them at the dosages and durations that have been studied. As a general rule of thumb, try only one new supplement at a time. This way you know which one is responsible for its desirable (or harmful) effects. Finally, just because it doesn’t require a prescription, that doesn’t mean that it’s safe! At a high enough dose, everything is a poison. Let the (brain) gains begin!


Natural Standard: Food, Herbs & Supplements. Somerville, MA: Natural Standard Corporation; [n.d.].,-herbs-supplements.aspx. Accessed January 19, 2017.
de los Reyes GC & Koda RT. Determining hyperforin and hypericin content in eight brands of St. John’s wort. Am J Health Syst Pharm. 2002 Mar 15;59(6):545-7. PMID: 11908248
Cooper R. & Kronenberg F. (Eds.). Botanical Medicine: From Bench to Bedside. Pennsylvania, USA: Mary Ann Liebert, Inc.;2009.