Dear Osa friends,

The warmer spring weather is ushering in a wandering summer energy, and I hope you can harness it to try some new avenues in your health journey in the coming weeks and months. Maybe this post will even give you an idea or two!

We’re continuing a discussion of satiety and GLP-1 that we began last fall, when I wrote this post about the relationship between short-chain fatty acids (produced by your very own gut microbiome) and GLP-1 production.  In that post, I also touched just briefly on protein and satiety. Here we’re going to dig deeper into that topic and learn more about our body’s hormone response to food and how we can personalize our nutrition to optimize this.  Let’s get to it!

GLP-1 Secretion: Two Phases!

It’s not often talked about, but your body’s production of the satiety hormone GLP-1 occurs in two phases.  When we spoke about short-chain fatty acids and GLP-1 release in the previous post, this was referring to the second phase of GLP-1 production, which occurs one-to-two hours after eating. The first phase, which occurs within 15-30 minutes of eating, is thought to be influenced primarily by nutrient sensing of proximal intestinal cells.¹  Pretty amazing, right?

This first phase release is important because it is related to the first phase release of insulin, which helps to produce a more steady rise and fall of blood glucose.  When we have a poor first-phase insulin release, we can experience a sharper increase in blood glucose after eating, and this can be followed by a sharper decline in blood glucose afterward. These spikes and dips can make you feel sleepy after eating, and they are also a significant source of unnecessary stress for the body.  The first phase GLP-1 response is also important because we want satiety to occur within a reasonable time frame after eating, and this first phase response gets that ball rolling for us.  

We talked about fermentable fibers and their importance in the second phase of GLP-1 release, but what about the first phase? How can we optimize this first phase GLP-1 release?  Both nutrient intake and digestive awareness are key here, and we’re going to get into that. But first, let’s talk about why nutrients–not calories–matter most to you.

Nutrients > Calories

As a clinician, I care deeply about the long-term metabolic health of my clients.  For my clients, their goals often include feeling good after eating (getting rid of symptoms like reflux, bloating, excessive gassiness, bowel movement irregularity, etcetera), feeling satiated, having consistent energy throughout the day, sleeping better, and losing ten or more pounds of extra weight.  These are all related to metabolic health, and we can move the needle on all of these with personalized nutrition.  But first, we need to understand and really internalize how the body works. This deeper understanding allows us to move beyond the “I just need to eat less and move more” nonsense that still occupies space in our concept of health, despite the fact that our physiology (and perhaps our gut feelings too) tells us there’s much more to the story than calories.

Many factors are involved in the body’s energy sensing system which causes us to dial up or down our food seeking behaviors.  Microbiome health is a big one which we’ve talked about in past posts (and will continue to talk about in the future!).  The nutrient sufficiency of our foods and our own unique nutrient needs are other big factors that can get overlooked when we are overly focused on calorie restriction.  The idea that one can simply eat less and lose weight is overly simplistic, blind to the mismatch between modern life and our evolutionary biology, and frankly disrespectful to all people who struggle to feel well in their own skin.

Here’s the thing: the body needs nutrients to function, whether it is carrying excess fat or not. If the body is not getting enough of any one thing it needs (proteins and micronutrients are big ones to factor in), it is likely to upregulate hunger signaling.

Amino Acids and GLP-1

A number of nutrient factors have been investigated in their relationship to GLP-1 secretion. Today we’re using amino acids to illustrate the importance of nutrients and digestion in satiety signaling.  Protein has been enjoying its time in the macronutrient limelight recently, but less time is spent talking about how much of specific amino acids–the building blocks of proteins–we require.  Yet it is amino acids that our bodies use for building cells and enzymes and bone, and sometimes for energy too.  When we look at what we know about how protein stimulates GLP-1 in the nutrient-dependent “first phase” release, two amino acids have emerged from the research thus far as GLP-1 stimulants: glutamine and arginine.  Interestingly, these two amino acids are both considered to be “conditionally essential.”  What is the significance of this? 

Out of the twenty amino acids, nine are considered “essential,” meaning we need to get them from our diet because the body cannot produce them from other amino acids, and two more (glutamine and arginine) are considered “conditionally essential,” meaning that they become essential when the body is in conditions that outpace its ability to synthesize them.  Conventionally, conditions under which glutamine and arginine are considered essential include burns, other injury, surgery, severe illness or physical trauma.

But with so many people experiencing food cravings and various gastrointestinal symptoms including bloating, food sensitivities, and bowel irregularity, it seems plausible that many are living in conditions that are effectively depleting these amino acids, thereby rendering them “essential”.  

What do we need glutamine and arginine for? Glutamine is particularly important for the integrity of the intestinal cells that comprise the gut barrier, which is crucial to keep our immune system calm and inflammation in check.  Given the number of assaults on our gastrointestinal tract—food additives and irritants, psychological stress, infections, toxins–it is not a stretch to venture that many people could use more glutamine.  And, glutamine is a precursor to arginine–meaning that if glutamine is in good supply, the body will shuttle some of it into a pathway for arginine production. Arginine is a precursor to the powerful vasodilator nitric oxide and is particularly important for blood flow and wound healing.

What does all of this have to do with GLP-1 production anyway?

There is some evidence from clinical trials that glutamine, when given at a hefty dose of 30 grams, acutely stimulates the first-phase GLP-1 secretion, in people with and without diabetes.^2,3  There is also limited evidence that a much lower dose of arginine (~3 grams) results in increased GLP-1 response when given with a meal, compared to the same meal given without the arginine.^4,5 

Am I saying that you should start taking supplemental glutamine and/or arginine? No, I’m not saying that! (Also please refer to my medical disclaimer*: none of this is to be misconstrued as medical advice).  However, I do think that this gives us some food for thought about the connections between our food, our digestive health, and our cravings.  This information about glutamine and arginine is one piece of information in a very large sea, so take it with a large grain of salt.  But also, knowing that individual amino acids, among other nutrients, have an influence on our satiety signaling, we can begin to see how the health of our digestion plays a role in our blood sugar regulation and our cravings.  It is only with healthy digestive capacity that our bodies can break down dietary proteins into usable amino acids. So before reaching for another supplement that you hope will be a quick fix (spoiler alert: quick fixes are rare to nonexistent), I encourage you to

Get curious about the health of your digestive tract by considering a few things:

1. Stomach acid: The breakdown of proteins into their constituent amino acids requires robust stomach acid, which declines with age and with use of acid-blocking medications, which are very commonly prescribed.  Keep in mind that upper gastrointestinal complaints such as reflux can be related to low or high stomach acid.
   
2. Pancreatic function and small intestinal health: Protein digestion that began in the stomach is completed by the teamwork of enzyme secretions from the pancreas and from cells of the small intestine.  If any of these is working suboptimally, our ability to absorb nutrients (including amino acids) from food is significantly impaired.
   
3. Insults to the intestinal barrier: Stress (psychological and physical stress), illness, antibiotics and NSAIDS, environmental toxins, and food additives all have a negative effect on our intestinal lining and may increase our need for glutamine. Glutamine is a particularly important fuel for the cells of the small intestine, where most nutrient absorption occurs.

How can you tell if your digestion is suboptimal?

Stool testing, such as a GI-Effects from Genova Diagnostics, can provide a lot of specific data.  We can also obtain information on your assimilation of nutrients by assessing your dietary intake (hello, Cronometer!) alongside intracellular micronutrient testing, such as from SpectraCell or Vibrant lab providers. Some information can also be gleaned from a careful survey of symptoms. 

Ask yourself: Does my breath smell? Do I experience reflux? Are my stools particularly stinky, or greasy, or floating? Do I have stinky gas? Gastrointestinal upset after eating? Do you experience frequent skin rashes or ezcema? These are all signs your digestive system is sending you that lets you know it needs support. 

Sometimes we can reverse dysfunction with foundational nutrition and lifestyle approaches; other times we need more data to ascertain exactly what is going on.  I trust your gut, and you should too. You know when something is off. There are solutions within reach!

1. Theodorakis, M. J., Carlson, O., Michopoulos, S., Doyle, M. E., Juhaszova, M., Petraki, K., & Egan, J. M. (2006). Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. American journal of physiology. Endocrinology and metabolism, 290(3), E550–E559. https://doi.org/10.1152/ajpendo.00326.2004 https://pubmed.ncbi.nlm.nih.gov/16219666/
2. Samocha-Bonet, D., Wong, O., Synnott, E. L., Piyaratna, N., Douglas, A., Gribble, F. M., Holst, J. J., Chisholm, D. J., & Greenfield, J. R. (2011). Glutamine reduces postprandial glycemia and augments the glucagon-like peptide-1 response in type 2 diabetes patients. The Journal of nutrition, 141(7), 1233–1238. https://doi.org/10.3945/jn.111.139824 https://pubmed.ncbi.nlm.nih.gov/21593352/ 

2. Greenfield, J. R., Farooqi, I. S., Keogh, J. M., Henning, E., Habib, A. M., Blackwood, A., Reimann, F., Holst, J. J., & Gribble, F. M. (2009). Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects. The American journal of clinical nutrition, 89(1), 106–113. https://doi.org/10.3945/ajcn.2008.26362 https://pubmed.ncbi.nlm.nih.gov/19056578/ 
3. Amin, A., Neophytou, C., Thein, S., Martin, N. M., Alamshah, A., Spreckley, E., Bloom, S. R., & Murphy, K. G. (2018). L-Arginine Increases Postprandial Circulating GLP-1 and PYY Levels in Humans. Obesity (Silver Spring, Md.), 26(11), 1721–1726. https://doi.org/10.1002/oby.22323 https://pubmed.ncbi.nlm.nih.gov/30358156/ 
4. Yanni, A. E., Kokkinos, A., Binou, P., Papaioannou, V., Halabalaki, M., Konstantopoulos, P., Simati, S., & Karathanos, V. T. (2022). Postprandial Glucose and Gastrointestinal Hormone Responses of Healthy Subjects to Wheat Biscuits Enriched with L-Arginine or Branched-Chain Amino Acids of Plant Origin. Nutrients, 14(20), 4381. https://doi.org/10.3390/nu14204381 https://pubmed.ncbi.nlm.nih.gov/36297065/ 

*Disclaimer: This does not constitute medical advice and is for general informational purposes only. Please consult with your healthcare provider to determine whether diet, supplement, or lifestyle changes are right for you.

Photo by Alina Chernysheva on Unsplash