Effects of L-Phenylalanine on Energy Intake and Glycaemia-Impacts In Healthy Adults

[Lokzo]

Effects of L-Phenylalanine on Energy Intake and Glycaemia-Impacts on Appetite Perceptions, Gastrointestinal Hormones and Gastric Emptying in Healthy Males​

Penelope C E Fitzgerald 1, Benoit Manoliu 1, Benjamin Herbillon 1, Robert E Steinert 2, Michael Horowitz 1, Christine Feinle-Bisset 1
Affiliations expand

• PMID: 32560181
• PMCID: PMC7353198
• DOI: 10.3390/nu12061788

Free PMC article

Abstract​

In humans, phenylalanine stimulates plasma cholecystokinin (CCK) and pyloric pressures, both of which are important in the regulation of energy intake and gastric emptying. Gastric emptying is a key determinant of postprandial blood glucose. We evaluated the effects of intragastric phenylalanine on appetite perceptions and subsequent energy intake, and the glycaemic response to, and gastric emptying of, a mixed-nutrient drink. The study consisted of two parts, each including 16 healthy, lean males (age: 23 ± 1 years). In each part, participants received on three separate occasions, in randomised, double-blind fashion, 5 g (Phe-5 g) or 10g ('Phe-10 g) L-phenylalanine, or control, intragastrically, 30 min before a standardised buffet-meal (part A), or a standardised mixed-nutrient drink (part B). In part A, plasma CCK and peptide-YY (PYY), and appetite perceptions, were measured at baseline, after phenylalanine alone, and following the buffet-meal, from which energy intake was assessed. In part B, plasma glucose, glucagon-like peptide-1 (GLP-1), insulin and glucagon were measured at baseline, after phenylalanine alone, and for 2 h following the drink. Gastric emptying of the drink was also measured by 13C-acetate breath-test. Phe-10 g, but not Phe-5 g, stimulated plasma CCK (p = 0.01) and suppressed energy intake (p = 0.012); energy intake was correlated with stimulation of CCK (r = -0.4, p = 0.027), and tended to be associated with stimulation of PYY (r = -0.31, p = 0.082). Both Phe-10 g and Phe-5 g stimulated insulin and glucagon (all p < 0.05), but not GLP-1. Phe-10 g, but not Phe-5 g, reduced overall plasma glucose (p = 0.043) and peak plasma glucose (p = 0.017) in response to the mixed-nutrient drink. Phenylalanine had no effect on gastric emptying of the drink. In conclusion, our observations indicate that the energy intake-suppressant effect of phenylalanine is related to the stimulation of CCK and PYY, while the glucoregulatory effect may be independent of stimulation of plasma GLP-1 or slowing of gastric emptying.

 

[aliml]

CCK is a gut hormone that’s mainly released in response to a fat-rich meal. Long chain fats are especially potent CCK inducers. A high protein diet also increases CCK.

CCK: The Bad

People with IBS are more likely to release too much CCK (a gut hormone) in response to a fat-rich meal.

CCK is the culprit that causes gas soon after eating.

This might be because CCK activates the vagus nerve or because CCK directly interacts with the hypothalamus to stimulate the flow of your colon, which will cause gas.

CCK increases bloating and decreases stomach acid secretion, which slows digestion. It decreases stomach acid by increasing bicarbonate.

Regarding IBS, CCK causes gut pain hypersensitivity.

In humans, CCK causes nausea and anxiety. In fact, in the research, it’s used to induce panic attacks in people.

CCK activates your stress response.

Specifically, CCK increases CRH (bad stress hormone) prolactin (anxiety hormone), ACTH and cortisol. More ACTH is released in response to CCK when CRH is present. It also increases aldosterone secretion, which will increase blood pressure and cause salt retention.

If your stress response is activated chronically (chronic CRH), that makes the anxiety effects of CCK worse and this leads to ‘hypersensitive emotional circuitry’. This is the case even if CRH isn’t elevated at the time of CCK secretion.

More interestingly, CCK causes sleepiness/fatigue (despite the fact that it activates orexin).

CCK inhibits hypothalamic noradrenaline transmission, which is a plausible mechanism for CCK’s fatigue-inducing an appetite-suppressing effect.

CCK: The Good

CCK was the first gut hormone reported to affect appetite and has been shown to dose-dependently reduce food intake and causes satiation. It rises within 15 min after a meal.

Part of the satiating effect from CCK comes from it inhibiting NPY, which is a hunger hormone but is also an anti-anxiety peptide. So NPY is good to have balanced.

Another mechanism by which it causes satiation is by increasing leptin in the hypothalamus.

CCK slows the rate in which contents are emptied from the stomach, which is good for blood sugar control.

CCK also increases the production of bile and the release of pepsinogen, which converts to pepsin (when combined with HCL). Pepsin helps us break down proteins. It also increases other digestive enzymes, which help the digestion of fat, protein, and carbohydrates.

CCK stimulates the vagus nerve, which has multiple effects on the body, most of which are positive.

CCK increases oxytocin.

CCK plays a protective and anti-inflammatory role in the kidneys. In other cells (peritoneal), it reduces Nf-kB and nitric oxide production.

CCK can increase memory in humans and rats. In particular, it helps verbal and ‘aversive’ memory (aversive memory=quicker learning of avoiding the bad).

CCK is released in the brain in a circadian rhythm. Lithium increases CCK in the brain and this is part of the mechanism by which lithium prevents mania in bipolar.

CCK increases AMPK in the muscle, which allows it to have more fuel. AMPK activation in muscles prevents them from growing too large, however.


The following food components have been shown to maximize CCK release:

Fat – most important
Protein
Soluble fiber

Highest Ranking, Satiety Inducing Foods (which will be correlated with CCK release):

Potatoes 323% Contains Pot-II protein, shown to stimulate CCK release
Fish 225% High in protein, shown to stimulate CCK release
Oatmeal 209% High in soluble fiber, shown to stimulate CCK release
Oranges 202% High in pectin, shown to stimulate CCK release
Apples 197% High in pectin, shown to stimulate CCK release
Brown Pasta 188% High in soluble fiber, shown to stimulate CCK release
Beef 176%. High in protein, shown to stimulate CCK release
Baked Beans 168% High in soluble fiber, shown to stimulate CCK release
Grapes 162% High in pectin, shown to stimulate CCK release
Whole-Grain Bread 157% High in soluble fiber, shown to stimulate CCK release.

Realize that CCK is not the only factor that induces fatigue after meals, so this is not an exact ranking of how tired you will feel after a meal.

CCK Positives & Negatives, Function & Lectin Sensitivity - SelfHacked

CCK is linked to post-meal fatigue, IBS, & lectin sensitivity. Learn more about the positive & negatives of CCK & it's role in lectin sensitivity.

selfhack.com

 

[Mauritio]

I find phenylalanine to be one of the most reliable supplements in terms of dopamin increase and reducing constipation.

It also seems to have a vasodilator effect on me, similar to magnesium .

 

[Lokzo]

I find phenylalanine to be one of the most reliable supplements in terms of dopamin increase and reducing constipation.

It also seems to have a vasodilator effect on me, similar to magnesium .

Yes, Phenylalanine is incredible for correcting a low baseline dopamine state due to extreme binging or bursting dopamine levels too high.
I really want to wear a CGM and run some big experiments with high dose Phenylalanine.

 

[Ismail]

I find phenylalanine to be one of the most reliable supplements in terms of dopamin increase and reducing constipation.

It also seems to have a vasodilator effect on me, similar to magnesium .

How much do you take to reach this effect?

 

[Lokzo]

How much do you take to reach this effect?

750mg

 

[Ismail]

750mg

Empty stomach? One dose?

Thanks bud (I’m still sulking cos you came to London and I didn’t see you lol! ?)

 

[Mauritio]

How much do you take to reach this effect?

For me 400 or 500mg is the sweet spot.

 

[Ismail]

For me 400 or 500mg is the sweet spot.

Thanks bud, do you take it on an empty stomach?

 

[Mauritio]

Thanks bud, do you take it on an empty stomach?

No I found it more effective after a meal.