Choline: The Scottie Pippen of Micronutrients

https://www.researchgate.net/figure/Choline-metabolic-pathway-Choline-is-an-essential-biological-molecule-for-all-cells-and_fig2_335957266

When I say the word micronutrient, what comes to mind? Maybe Calcium, Magnesium, Potassium, Vitamins A-D? But what about Choline? Unless you read nutrition research or scrutinize nutrition labels, you may have never heard of Choline. I liken this masterful micronutrient to Scottie Pippen of the great 90s Chicago Bulls dynasty. You ask anyone about those Bulls teams and they will give you one name and one name only: Michael Jordan. Yes, Jordan was unbelievable, but so was Pippen. Choline is a workhorse that deserves credit, but instead hides behind the mighty shadows cast by the big name micronutrients.

It has seemed that after ESPN’s new Bulls documentary that Pippen has been given more recognition, but unfortunately, I don’t see a choline documentary coming anytime soon. So I guess this article will have to suffice.

Choline has numerous functions within the body, but for simplicity I will broadly cover three of them. Once choline enters the intracellular environment, it is typically “worked on” by three different enzymes.

  1. Conversion to betaine. The enzyme choline oxidase irreversibly oxidizes (adds bonds to oxygen) choline while also producing one equivalence of hydrogen peroxide. This creates the well-known pre-workout ingredient, betaine. Why is this important? Well, other than being an ingredient hap hazardously thrown into a pre-workout cocktail, betaine has shown some incredible promise as of late.

A new study (in mice) demonstrates that betaine supplementation (3x the normal dose) actually reduces schizophrenic symptoms (1).

One of the main genes involved in schizophrenia is Kif3b, a member of the kinesin family. Kinesin, a motor protein, is needed to carry cellular machinery away from the neuronal cell body. Kif3b typically links up with another kinesin superfamily and together function by moving cellular machinery throughout the cell.

Through recent work, researchers in Tokyo demonstrated that Kif3b mutants (to mimic schizophrenia) exhibit this weird branching pattern during growth, which they call lamellipodial dynamics (it almost looks like the neuron is dancing). The inside of a normal, healthy neuron fills with tubulin, which typically interacts with actin, to continue a normal branching pattern. However, due to the weird branching of the mutant Kif3b, the lamellipodial dynamics are reduced, and actin is not able to interact with tubulin as efficiently as possible.

This incomplete interaction between actin and tubulin leaves actin susceptible to carbonyl stress damage (specifically in the CRMP2 portion of the actin structure). This causes the proteins to clump together. This then reduces the efficiency and efficacy of Kif3b leading to the typical schizophrenia symptoms (or at least contributing to them). Yet, betaine supplementation prevents carbonyl stress on CRMP2 and thus impedes the clumping of proteins, thereby allowing Kif3b proteins to build proper structures and function thoroughly.

Obviously testing needs to be done in humans, but betaine is a safe compound and is especially worth looking into when we consider the crazy adverse side effects of most typical schizophrenic treatments.

2. Conversion to acetylcholine. Surely, if you have taken an intro bio or psych class, you have heard of the neurotransmitter acetylcholine. In brief, thanks to other metabolic processes (the Krebs cycle and fatty acid oxidation, specifically) our body has these potent 2 carbon molecules called Acetyl-CoA at its disposal. The enzyme, choline-acetyltransferase is able to grab the acetyl group off of Acetyl-CoA and transfer it to choline to create acetylcholine. This imperative neurotransmitter has a multitude of functions, but of note it is essential for muscular contractions.

https://en.wikipedia.org/wiki/Acetylcholine#Functions

Let’s say you want to perform a biceps curl. You think “contract my biceps” and motor neurons located in your spinal cord and/or brainstem (label A in the picture) will propagate an action potential through its axonal projections to motor nerves. This action potential will move through the motor nerves to reach an axon terminal (label B in the picture) in which the change in electrochemical gradient causes an influx of calcium ions, thus triggering the release of acetylcholine. Acetylcholine then travels across the synapse (label C) in what we call the neuromuscular junction. The acetylcholine molecules then bind to nicotinic ion-channel receptors (label 4 in the picture) on the muscle cell membrane, causing the ion channels to open. Sodium ions then flow into the muscle cell (label 5 in the picture), initiating a sequence of steps that finally produce muscle contraction (label 6 in the picture).

3. Conversion to sphingomyelin. Through the Kennedy Pathway and many enzymatic reactions, choline is converted to sphingomyelin. Sphingomyelin is crucial for the integrity of our cellular membranes, signal transduction, and triggering apoptosis (cellular death) of damaged cells (amongst other functions).

Wow choline does a lot…and I did not even touch on its role in dopamine metabolism…our endogenous pleasure drug, or its role in memory.

Adult men and women need 550 mg and 425 mg of choline per day, respectively, but 90% of the U.S. population does not meet this recommended intake (2,3).

So, now you are probably thinking, “Man, choline seems pretty important, I definitely want to get my hands on some…how do I do that?”

Great question. Some great food sources are:

A) Whole eggs (1 whole egg =147mg choline; 4)

B)Salmon (3 ounces=187 mg choline; 5)

C) Beef liver (3 ounces cooked = 240 mg; 6).

Or…you could purchase the Pinnacle Supplementation Multivitamins. The men’s pack is of course locked and loaded with 550mg choline per serving, and the women’s has 425 mg. To my knowledge, Pinnacle is one of the only (if not the only) supplement company to provide a multivitamin with the proper dosing of choline to make a meaningful difference (based on recommended daily intake). And trust me, it is literally my job to be on top of this stuff.

So, now that I have brought choline into the limelight, let’s help it stay there by downing some eggs, buying some Pinnacle products, and telling a random stranger on the street how cool choline is.

Post-Baccalaureate research assistant in the Molecular and Clinical Nutrition Lab at the National Institutes of Health