Many of the chemicals on that list are neurotransmitters that are not at all surprising. There is currently plenty of exciting research going on trying to link the brain and gut together. This blog article will focus on CCK(cholecystokinin) and how it relates to our digestion.

Your heart begins to race. Your pupils dilate, your mouth becomes dry, you panic.  You race off to the bathroom with a sudden urge to evacuate your bowels. After you clean yourself up, you notice your stool was yellow, and you begin to feel calmer.

Digestion and anxiety attacks are strongly related. The two are linked in several different ways, and one of the most common links, is poor fat digestion, vagus overstimulation, and a little-known hormone called CCK.

What is CCK and What Does It Do?

CCK stands for cholecystokinin, and it is synthesized in the mucosal epithelium of the small intestine and secreted into the duodenum.^{1 2}  The release of CCK is stimulated by a peptide released by pancreatic acinar cells and, CCK-releasing protein secreted by enterocytes in the mucosa. Also, vagus nerve stimulation by acetylcholine may trigger its release. Finally, the greatest stimulator of CCK is the presence of fatty/amino acids in chyme when it enters the duodenum for further digestion.^{3 4}

The hormone does a lot in our body including:

• Stimulating the release of bile from the gallbladder and digestive enzymes from the pancreas.⁵
• Increases bile production by the liver.⁶
• Increases sodium bicarbonate production by the pancreas to neutralize stomach acid.⁷
• Slows down gastric emptying and decreases stomach acid secretion.⁸
• Induces satiety.⁹
• Increases opioid tolerance.¹⁰
• Plays a role in increasing sensitivity to pain.¹¹
• Reduces inflammatory markers including TNF and Il-6.¹²
• Increases aldosterone (a hormone that increases retention of sodium and increases blood pressure) and cortisol.^{13 14}
• Helps to regulate MMC function in conjunction with the hypothalamus.¹⁵
• Overproduction can lead to postprandial fatigue and sleepiness (the ITIS!)¹⁶

As the chyme, digestive enzymes, and bile pass further into the small intestine, cholecystokinin release diminishes. Also, more digestive enzymes produced by the pancreas to aid in digestion like trypsin and somatostatin further inactivate CCK.¹⁷

So What Does All This Have To Do With Anxiety?

A single cholecystokinin peptide known as CCK-4 is to blame.¹⁸  In someone that is healthy, most CCK peptides are broken down effectively in the digestive tract and they do not cross the BBB easily. When someone is having fat digestion issues, upper gut infections, SIBO, or leaky gut, CCK peptides are more likely to cross the BBB (specifically CCK-4).^{19 20} What does CCK-4 do when it gets into the brain? It overstimulates the vagus nerve for one and induces panic.²¹ Studies show that CCK-4, injected into the bloodstream, causes panic attacks. It is quickly metabolized in the brain, so the duration of its effects are short unless the act of panicking releases excess catecholamines which cause some people to have panic attacks for an extended amount of time.²²

CCK production, inactivation, and leaky gut issues can also cause rapid dumping syndrome in consuming foods that stimulate its release (mainly fat), which can also overstimulate the vagus nerve and create anxiety.²³ Capsaicin has been shown to at the very least blunt some of the effects CCK-4 has on the vagus nerve by desensitizing it and reducing anxiety.²⁴ Digestive enzyme supplements that include amylase and trypsin might also reduce CCK overproduction in the intestines by activating feedback loops within the body.

So CCK Is Not Really To Blame For Digestive Anxiety, Right?

Correct.

The problem with digestive anxiety is not CCK but instead either an overproduction of CCK from digestive concerns, or leaky gut. Most of the time too much CCK will be produced when you either eat a high-fat meal (if you are not “fat adapted”) or have some issue with your organs that help aid in fat digestion (liver, gallbladder, stomach, and pancreas). Fat malabsorption can also cause diarrhea and in doing so overstimulates the vagus nerve which exacerbates anxiety.  Also, if you are suffering from leaky gut (more than likely from overgrowth) CCK peptides (including CCK-4) might be more likely to cross the BBB and induce anxiety. Try to reduce overgrowth and work to improve the lining of your intestinal barrier and restore your microbiome to good health.

When it comes to anxiety and digestion, do not blame the hormone CCK, which provides a lot of important functions within our body. Instead, work to improve your digestion so that CCK production maintains homeostasis to improve your overall health.

There are several endogenous chemicals affect digestion including:

• Serotonin
• CCK
• GIP
• Gastrin
• Secretin
• Motilin
• Dopamine
• Acetylcholine
• Gaba
• Ghrelin
• Leptin
• Histamine
• Melatonin