In previous blogs I’ve gone over using creatine and thiamine for gut health.  As I’ve seen the discussion evolve on the private facebook group, it’s clear that I need to discuss how they play a role in gut health.  If you’re interested in the group, you can request to join here.

There are a few mechanisms at play here.  First, creatine lowers methylation demands because creatine synthesis uses 40% of the methyl groups you make.  Second, creatine plays a pretty big role in giving you energy.

Thiamine also plays a big role in giving you energy.  To efficiently use glucose for energy, you need adequate thiamine.  This is a big deal because neurons get the vast majority of their energy from glucose.  This is evident because thiamine deficiency presents as neurological problems.

The enteric nervous system

Creatine and thiamine come to a crossroads in every cell in the body.  This crossroads gains importance when we look at neurons of the enteric nervous system.

The enteric nervous system is pretty interesting.  It more or less runs your digestive system.  It’s connected to your central nervous system via the vagus nerve but doesn’t need to be.

The vagus nerve allows your enteric nervous system and central nervous systems to communicate.  But, severing the vagus nerve doesn’t stopenteric nervous system function.  It plugs right along because the enteric nervous system isn’t dependent on the central nervous system like other systems.

The enteric nervous system runs everything in the gut.  Motility, enzyme output, everything.  It uses many neurotransmitters to communicate, but acetylcholine plays a dominant role there.  Especially when it comes to motility.

Every muscle in your body uses acetylcholine to contract, even smooth muscle in the gut.  This means that muscles in the gut are controlled by nerves that use acetylcholine, also called cholinergic nerves. Therefore, adequate acetylcholine synthesis is important for proper gut function.  Note: Acetylcholine also plays a starring role in the cholinergic anti-inflammatory reflex in the gut but we’ll save that for another time.

The synthesis of acetylcholine is dependent on the merging of 2 molecules: Acetyl CoA and choline.  Acetyl CoA is the point where creatine and thiamine come to a crossroads in gut health.  Maintaining adequate cellular levels of creatine and thiamine are required for optimal gut health.  So let’s find out how and why.

ATP-Cellular energy currency

Every cell in your body generates energy to power cellular functions.  Adenosine triphosphate(ATP) is the energy currency your cells use to get things done.

Taken from: https://meteormemory.files.wordpress.com/2015/12/atp-molecule.png?w=425&h=291

As you can see, ATP is just adenosine(adenine + ribose) attached to 3 phosphate groups.  When the bond between phosphates gets broken, it releases energy.  This leaves adenosine diphospahte(ADP) and a free phosphate.

The next bond can also be broken leaving you with adenosine monophosphate(AMP) and another free phosphate.  Or, the free phosphate can be re-attached to the ADP molecule to make ATP again.

Most of the energy in the ATP molecule is released when the bond between the 2nd and 3rd phosphate gets broken.  As such, we need a way to get that energy back, to recycle it.  This is where re-attaching a phosphate to ADP becomes important.

As you’re aware, food provides us with energy in the form of glucose and fatty acids.  What you may not know is that we don’t use the energy from food directly.  We use it to re-synthesize ATP from ADPby lending a phosphate.  But we don’t only use the calories in food to do this, we also use creatine.

Creatine-The phosphagen energy system

We store a lot of ATP in our cells, but nowhere near enough.  Since ATP levels are quite low in relation to our total daily energy needs, we must re-synthesize it continually.  The most readily available source for re-synthesizing ATP is creatine phosphate.

The process of making creatine is simple.  First, you combine arginine and glycine to form guanidoacetate.  Guanidoacetate is then methylated to form creatine.  A phosphate group is then tacked on to form creatine phosphate.

Taken from: https://www.mdpi.com/jcm/jcm-08-00488/article_deploy/html/images/jcm-08-00488-g001.png

Creatine phosphate can now donate a phosphate to ADP to form ATP.  So, creatine phosphate donates a phosphate to recharge ATP to be used for energy demanding processes.

Keep in mind, as the diagram shows, adding a phosphate to creatine requires ATP.  It’s not about how much energy you get from creatine, it’s about how quickly you can recharge ATP with it.

The primary benefit of using creatine as a way to recharge ATP is that it’s done quickly. There are 3 reasons for this.  One, creatine recharges ATP in the cytosol, it doesn’t need to be transported in to the mitochondria like glucose and fat and transported back out.  Second, it doesn’t use oxygen so it’s not dependent on oxygen being present in the cell.  Third, there’s a lot of creatine in cells.

Taken from: http://images.slideplayer.com/25/8092039/slides/slide_1.jpg

In this diagram of a cell, you can see the cytosol.  It’s the blue fluid that all the organelles float around in.  Since organelles use the bulk of ATP, a lot of ATP must be available in the cytosol.

Having ATP recharged by creatine in the cytosol is quick and efficient.  But, the total ATP yield from creatine is low in relation to what’s made in the mitochondria from glucose.

The drawback of creatine is that it can’t maintain ATP levels for long.  It can recharge ATP quickly but it can’t recharge a lot of it.  In terms of physical effort, if you were to explode in to a maximum effort sprint, creatine could recharge ATP in your muscles for about 10 seconds.

This may not seem like a long time.  But when you factor in that a typical neuron fires about 200 times per second you get an idea of how important creatine is for recharging ATP in a neuron.  But, it’s limited and once creatine phosphate donates its phosphate to ATP you need more ATP to add a phosphate back to creatine.  This is where glucose comes in.

Glycolysis-The next step in recharging ATP

The gears of a bicicyle are a good analogy to understand how cellular energy systems compliment each other.  If we look at using ATP directly for energy, that’s gear 1.  Gear 2 would be using creatine phosphate to recharge ATP.  Gear 3, the next step on our journey, involves glucose.

Using creatine phosphate as a means to recharge ATP is a 1 for 1 process.  This means that for every molecule of creatine you use to donate a phosphate, you only recharge 1 ATP.  You also use an ATP to add a phosphate to creatine so it’s a push.  Creatine is just storing a phosphate to provide to ADP quickly.  This is why it’s limited in its capacity to recharge ATP.  It’s fast, it works, but there’s not enough of it.  Enter glucose.

Glucose gives you a lot more bang for your buck.  A single glucose molecule can recharge 30 ATP molecules.  The first step in this process occurs in the cytosol without oxygen, just like creatine.  This process is called glycolysis.

Taken from: http://www.citruscollege.edu/lc/archive/biology/PublishingImages/c07_03.jpg

Glycolysis begins when glucose enters the cytosol of the cell.  Each glucose molecule is broken down in to 2 pyruvate molecules to yield ATP.

The first step in the process uses 2 ATP while 4 ATP get generated leaving a net of +2 ATP.  Note: Another molecule called NADH is also formed during glycolysis, but to keep this simple I’ll just stick to the glucose/pyruvate parts.  Eventually, NADH recharges ATP in the electron transport chain but you don’t really need to know that part to understand where I’m going.

What happens next is dependent on whether there is oxygen or not.  Without oxygen, pyruvate gets converted in to lactate.  Lactate either gets converted back to pyruvate when oxygen becomes available or transported out of the cell and sent to the liver where it’s converted back to glucose.

If there’s enough oxygen, a completely different process unfolds.  Pyruvate gets shuttled in to the mitochondria, the organelle where most ATP is recharged.  The first step in this process is the conversion of pyruvate to acetyl CoA by the pyruvate dehydrogenase complex(PDC).

The first enzyme in this complex is pyruvate dehydrogenase(PDH).  It’s the rate-limiting step in the pathway and requires thiamine as a cofactor.

Taken from: http://www.derangedphysiology.com/php/Acid-Base-Disturbance/images/diagram%20of%20lactic%20acidosis…

To convert pyruvate in to acetyl CoA, thiamine is a necessary cofactor as is lipoic acid.  Without these steps, you can’t make acetyl CoA so you can’t make acetylcholine.

Another problem is that you need to convert pyruvate in to acetyl CoA to get the rest of the energy out of glucose.  Without converting pyruvate to acetyl CoA, you lose out on the remaining 28 ATP you would have generated in the Krebs/citric acid cycle.  It’s also important to know that an acetyl CoA molecule can’t be used to synthesize acetylcholine AND recharge ATP.  It’s one or the other.

In the interest of brevity, we can stop here to understand why creatine and thiamine are important.  In most other cells, fatty acids are used for energy so they provide a 4th gear.  They can also from acetyl CoA without PDH and thiamine.  The problem is, fatty acids aren’t metabolized to a significant extent in neurons.

Smooth shifting between the creatine and glucose energy systems

Now we get to my analogy of gears on a bicycle.  Assuming you’ve ridden a bike before, shifting gears sequentially allows your ride to go smooth. You’re able to accelerate efficiently or maintain your speed with little effort.

If you were to switch from 1st to 3rd gear instead of 1st to 2nd, you’d struggle to provide enough energy to make that transition.  The result is a sharp decrease in speed as you try to generate enough torque to get the wheels moving.

In the same way, inadequate creatine levels prevent a smooth transition in recharging ATP.  This will cause a lag in energy production which will impair nerve firing.  As someone who responds well to creatine from a strength perspective, I can tell you this is pretty significant.  I can expect a 10-20% strength increase in as little as 2 weeks using creatine.  That’s huge in an old dog like myself.

Another issue with inadequate creatine is that ATP will need to come from glucose.  While some of this can come from glycolysis in the cytosol, this isn’t enough.

The alternative is to use acetyl CoA which happens to a significant degree anyway.  But in this instance, it’s either going to be stolen from acetylcholine synthesis or you just aren’t going to get the nerve to fire properly.  Neither situation is good.

Creatine and thiamine from a gut perspective

Now that we’ve gone through all that, let’s just imagine what this could do to gut motility.  We need both acetylcholine and energy for a cholinergic nerve to fire and for smooth muscle to contract.  Let’s assume you have adequate creatine but inadequate thiamine.

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Taken from: http://pubs.niaaa.nih.gov/publications/arh27-2/IMAGES/Page138.gif

This is a double-edged sword.  You get 2 ATPs before you get to pyruvate dehydrogenase, but lose 28 ATP and can’t make acetylcholine.  We know for a fact that neurons can’t rely on creatine and glycolysis in the cytosol because neurons die without oxygen.  They rely on the conversion of pyruvate to acetyl CoA by PDH and thiamine for survival.

As you can tell by the diagram, acetyl CoA is also required for myelin synthesis.  Myelin is the sheath that surrounds nerves.  It acts as a signal amplifier so poor thiamine status can affect nerve transmission that way as well.

Less energy+poor nerve transmission+sluggish smooth muscle contraction=slow gut motility

Now let’s assume that we have inadequate creatine and adequate thiamine.  From a total ATP perspective this may not seem like a big deal.  But remember, nerves fire 200 times a second and creatine is the quickest way to recharge ATP.

This may lead to a lag in nerve firing which will lower the strength of a muscular contraction.  The number of times a nerve fires dictates how strong a muscular contraction is and whether it’s smooth or spastic.  Strong and smooth are ideal.

The other big issue is that acetyl CoA that could have gone towards acetylcholine synthesis now has to go towards generating ATP.  Neurons use up a ton of energy because they need to move a lot of different ions around to fire which requires a lot of ATP.  Even just a small disturbance in energy can throw off nerve transmission.

Less energy+poor nerve transmission+sluggish smooth muscle contraction=slow gut motility

For proper gut motility, you need nerves to fire properly.  Cholinergic nerves are in control of regulating muscular contraction so they are front and center in gut motility.  These nerves need acetylcholine AND a lot of energy to fire.

They also need a seamless flow of energy from fast and slower energy sources.  Creatine and thiamine are 2 nutrients that play big roles in motility.  Making sure your cells are adequately equipped with both can be a huge help in improving sluggish motility.

Conclusion

Both creatine and thiamine are important for efficient firing of nerves and muscular contraction.  Inadequate levels of either or both will impair gut motility.

There are many reasons you may be deficient in creatine or thiamine.  Foods don’t contain a lot of creatine and the only foods that do are of animal origin.  You make creatine but the process requires a lot of methyl groups.

People with SNPs in the choline, folate, and methlyation pathways may not have optimal creatine levels.  There are also SNPs in the creatine synthesis pathway that can reduce creatine levels in cells.

With thiamine, a person’s thiamine needs are dictated by the amount of carbohydrate they consume.  People who consume a high carbohydrate diet need more thiamine even if they meet the RDA because total glucose oxidation is dependent on thiamine.

Exercise also affects thiamine requirements.  The more intense exercise you perform the more you rely on glucose for energy.  People who exercise require more thiamine than a sedentary individual.  And trust me, you absolutely should be exercising.

The final and most probable sign that you don’t get adequate thiamine is removing processed food from your diet.  Removing processed food is an effective strategy for weight loss and improving digestive problems.

But, processed foods are fortified with thiamine making them the most significant source of thiamine in the Western diet.  Removing them without making a concerted effort to eat other foods high in thiamine can cause deficiency.

It’s not hard to see how this process plays out in relation to fatigue.  Creatine gets synthesized in the liver and distributed to tissues.  A defect in creatine synthesis won’t just affect the gut, it will affect total body energy.  In the same way, low thiamine status will have a systemic effect on energy levels.

Digestive problems and fatigue seem to go hand in hand.  The assumption is that someone who’s not digesting their food is probably in an energy deficit.  The implication is that the lack of digestion is causing a lack of cellular energy, but what if it’s actually the other way around?  A little food for thought.

Like this blog?  Have you given creatine or thiamine a try and have something to say about it?  Do you have questions that weren’t answered in the blog?  Drop a comment or question in the comment section below.  Also, don’t forget to join the private facebook group here so you get access to private blogs and discussions as well notifications when new blogs are posted.