Based upon the title of this post and my disappearance from my writing and social life for the past couple of months, you may have your suspicions of a possible immersion in Scientology or striking up an acquaintance with Tom Cruise. Rest assured – this is not the case. While Tom Cruise once notoriously claimed that Brooke Shields’ postpartum depression could be cured by vitamins, I am here solely to enlighten and inform you of an extremely interesting take on an alternative treatment for depression I learned about in my Vitamins & Minerals course this semester….and to break down how it works.
Depression is a topic and condition that is close to my heart. Both close friends and family have struggled with mental illness at various times. Having always felt helpless in pulling them out of a spiral, it provided me with some solace in understanding how I might eventually be able to provide them relief through a scientifically-targeted and natural approach. Specifically, through nicotinamide, or niacin supplementation.
Depression, like many things in life and particularly health, is multifaceted.
There is not just one thing that causes it nor one thing that fixes it. In many cases, too, it’s a game of chicken-or-the-egg: Could depression and stress have triggered one’s physical symptoms, or would someone’s physical pains, diagnoses, and limitations have caused them to become anxious and depressed? The answer is, well, both. Further, they perpetuate each other. What a mess!
I’m sure most of you are familiar with or have heard of the neurotransmitter serotonin; its implication in depression and mood disorders is ubiquitous. In fact, anti-depressants classified as SSRIs (selective serotonin reuptake inhibitors) are designed to allow for a higher level of the neurotransmitter to continually circulate, which chemically enhances one’s mood as a result.
So, in getting at the root of this serotonin issue, let’s take a look at its biochemical pathway, shall we?
Serotonin is derived from the amino acid tryptophan, which is found in many foods – most popularly in what we eat on Thanksgiving. Tryptophan has two main fates in our body: it is a constituent of many proteins needed for various enzymes, and it is a substrate for two very important biosynthetic pathways. One of these pathways generates serotonin and the other is called the kynurenine pathway. The kynurenine pathway’s end result is the production of niacin, or vitamin B3, and nicotinamide adenine dinucleotides, which are integral in energy production. In a healthy individual, the funneling of tryptophan into these two pathways and also into protein production is nicely balanced. When one is inflamed, however, protein production and the serotonin pathway are greatly slowed down, and the majority of tryptophan is shunted to and degraded in the kynurenine pathway.
The reason for this is an adaptive, protective measure in response to an invading threat, which of course is always our body’s first intent when initiating any sort of inflammation. When pathogens (bacteria, viruses, etc.) enter the body, they feed on protein to grow and proliferate. In order to starve these bugs so the threat subsides, this inflammatory response hides tryptophan and places it in the kynurenine pathway. Smart, right? Yes.
However, when inflammation is prolonged, which is the case in all chronic illness, a sustained predominance of the kynurenine pathway leads to some negative repercussions. One of which is insufficiency of serotonin, which contributes to depression. And, since serotonin is a precursor for the production of melatonin, sleep disturbances soon ensue from lack thereof.
The Kynurenine Pathway
While this state of imbalance results in an insufficiency of serotonin, at the same time it produces an excess of certain kynurenine metabolites. If you look at the pathway above, you will see something called quinolate towards the end, which is a potent neurotoxin. Quinolate’s accumulation is often the reason we experience pain during viral infections, such as the flu. It’s also a reason why (cue the Cymbalta commercial) depression hurts. Quinolate also interacts with receptors in the brain that respond to pain, and, with too much of it circulating around, its excitatory stimulus can cause degeneration of neurons in the brain leading to loss of function. Such toxicity has been shown to be the case in stroke, Alzheimer’s, and dementia.
Ok, so where does niacin come in, you’re wondering?
Well, if you look at the pathway once more, you will see that the last stop on the kynurenine train is nicotinic acid (niacin, in other words). The whole enzymatic pathway functions as a negative feedback loop. For instance, say you had a hunger signal coming from your brain and your stomach is growling…this makes you want to eat and go searching for food, right? Once you’re full and satiated, this sends a negative feedback signal to your brain that says, “okay, you’re full, you no longer need to eat.” If you’re feeling full most of the time, you won’t be compelled to reach for the refrigerator. Similarly, if you supplement with nicotinamide (a form of niacin that doesn’t make your skin flush), this sends a negative feedback signal to the enzyme in charge of initiating the tryptophan steal into this pathway in the first place (IDO/TDO), and says, “well we have the end product we need in abundance, we really don’t need to move all the tryptophan into here anymore.” So, the enzyme turns off, tryptophan is no longer being sucked in there, and it becomes more available for its other pathway, and converts to serotonin. With more serotonin being synthesized, one’s depression essentially improves. I told you it was interesting.
Further, quinolinate production would consequently be reduced, giving your brain a break from all the toxic stimuli. In fact, a study on patients with HIV infection treated with nicotinamide increased plasma tryptophan concentration by 40%, without major side effects that are commonly seen with the administration of anti-depressants. It accomplished this by suppressing the enzyme activity that initiates the kynurenine pathway.
Obviously, this is by no means a cure-all for depression.
As I mentioned before, the reason why this metabolic detour occurs in the first place is because one is inflamed. Then it can initiate depression, which makes you more inflamed and even more depressed. Supplementation of niacin works by rewiring this vicious cycle while you address the main sources of inflammation to stop the detour from happening at the start.
There are many etiological factors of inflammation, which I plan to address in a future post on the allostatic load model. One of these is, of course, our many negative thoughts and feelings we have as a result of deep-rooted emotional patterns and daily struggles we experience in life. Psychotherapy is an essential tool in helping to reduce some of these loads. Where I or some other functional medicine practitioners would come in is to address the inflammation from all other angles in order to keep one afloat while they delve into their personal and emotional intricacies. We all have these.
On a personal note, I, too, experience bouts of depression related to managing, enduring, and trying to navigate and solve what is truly going on with my health for all of these years. It is a feeling of complete lack of control over my life and future at times where I am constantly treading water in my efforts to maintain being “Erin.” The lines get blurred as to whether my emotions are a result of all of these very stressful factors, or, if it is part of the picture itself. It also becomes an overwhelming undertaking to feel as though I would have to iron out all of my deep-rooted life events in order to become healthier. As I am learning each day, especially from the many downstream effects that inflammation has (specifically on this pathway), it starts to make more sense in knowing there’s a lot more to it than most people think. It’s also comforting to understand that.
So, if you or someone close to you suffers with depression or mental illness, it’s important to evaluate the entire health picture.
There could be underlying inflammation that could trigger, contribute to, or perpetuate one’s depression. Or, depression could lead to further health issues on its own. I guess I haven’t addressed the chicken-or-the-egg question yet!
Seeing a functional doctor or nutritionist, along with a great psychologist could definitely make things, well, a little brighter.
Have a great weekend and smile 🙂
- Schrocksnadel, K.; Wirleitner, B.; Winkler, C.; Fuchs, D. Monitoring tryptophan metabolism in chronic immune activation. Clinica Chimica Acta 2006, 364, 82-90.
- Lord, R. S.; Bralley, A. J. Laboratory Evaluations for Integrative and Functional Medicine, Revised 2nd Edition; Genova Diagnostics: Duluth, GA, 2012.