HoldsUp

Kyal Van Der Leest

LVLUP Health

Kyal Van Der Leest is associated with LVLUP Health. His work and discussions focus on peptides, metabolism, and GLP-1 support for health and weight management.

32 claims checked on air: 2 context 3 contradicted 5 overstated 22 supported

What they said on air - supported

0:08:35supportedhighPeptides to Support Your GLP1 Health And Weight Loss Journey

GLP-1 receptor agonists slow gastric motility and gastrointestinal transit.

"The reason this happens obviously is the GLP-1s affect gastric motility. They slow it down. They keep you feeling full for longer both in the brain and, you know, physically in the small intestine, the gut, and in your whole digestive tract." (said at 0:08:35)

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are well established to inhibit and slow gastrointestinal motility and prolong gastric emptying and small-bowel transit times, contributing to increased satiety alongside central nervous system effects.

0:10:10supportedmoderatePeptides to Support Your GLP1 Health And Weight Loss Journey

TUDCA thins bile, promotes bile flow, and acts as an antibacterial disinfectant in the small intestine.

"TUDCA. It's the bile acid. It's going to help with—it thins your bile, it helps bile flow, and bile is a really good disinfectant for the small intestine." (said at 0:10:10)

Tauroursodeoxycholic acid (TUDCA) is a hydrophilic conjugated bile acid recognized for its choleretic properties, promoting hepatic bile secretion and bile flow (often described colloquially as 'thinning' bile by increasing the hydrophilic bile acid pool and reducing cholestatic sludge/viscosity). Additionally, physiological bile and bile acids exert well-documented direct and indirect antimicrobial effects in the small intestine, helping prevent mucosal bacterial colonization and small intestinal bacterial overgrowth (SIBO). Clinical and experimental studies show that hydrophilic bile acids like UDCA and TUDCA stimulate bile production and improve intestinal dysbiosis/bacterial overgrowth.

0:21:45supportedhighPeptides to Support Your GLP1 Health And Weight Loss Journey

Caloric restriction and rapid weight loss trigger a reduction in thyroid function and metabolic rate.

"Well honestly, when GLP-1s like and any sort of weight loss, be it extreme dieting, caloric restriction, will usually result in suppression of your thyroid. It's just a survival mechanism. If calories in aren't enough, then the body reacts by saying, 'All right, we're going into preservation mode. So, we'll slow down the thyroid. We'll slow down our metabolism and make it harder for you to lose weight'" (said at 0:21:45)

Substantial evidence from randomized clinical trials demonstrates that caloric restriction and weight loss lead to metabolic slowing (adaptive thermogenesis) and down-regulation of thyroid hormone axis activity, characterized primarily by reductions in circulating triiodothyronine (T3). In the 2-year CALERIE trial, sustained calorie restriction led to a significant decrease in daily energy expenditure beyond what was expected from mass loss alone, alongside reductions in thyroid axis activity. Similarly, in dietary weight-loss trials such as POUNDS LOST and short-term severe caloric restriction studies, energy restriction consistently reduced resting metabolic rate and serum T3 concentrations.

0:23:01supportedmoderatePeptides to Support Your GLP1 Health And Weight Loss Journey

Adequate iron levels are required for proper thyroid function and thyroid hormone synthesis.

"Iron is so essential for thyroid function. And if you have leaky gut, if you've got damage to your gut, IBD, then you're not going to be absorbing iron well" (said at 0:23:01)

Adequate iron status is well established as essential for thyroid hormone synthesis and normal thyroid function. Iron serves as an essential cofactor for thyroid peroxidase (TPO), a heme-dependent enzyme required for the iodination of tyrosine residues in thyroglobulin to produce thyroxine (T4) and triiodothyronine (T3). A 2023 meta-analysis of observational studies confirmed that iron deficiency is significantly associated with lower concentrations of free T4 and free T3, as well as an increased prevalence of thyroid autoimmunity.

0:23:55supportedhighPeptides to Support Your GLP1 Health And Weight Loss Journey

Lactoferrin binds iron in the gastrointestinal tract and facilitates its absorption into the body.

"Lactoferrin is from colostrum and it binds iron in your gut and helps it absorb into the body." (said at 0:23:55)

The claim is supported by scientific evidence. Lactoferrin is a major iron-binding glycoprotein present in high concentrations in colostrum and breast milk. It binds iron with high affinity in the gastrointestinal tract and facilitates its transport and intestinal absorption via specific receptors on enterocytes (PMID: 7874020, PMID: 29756573). Clinical trials and isotope absorption studies demonstrate that lactoferrin supplementation (such as apo-lactoferrin combined with iron) significantly enhances fractional iron absorption and improves systemic iron status (PMID: 32886113, PMID: 34440102).

0:24:10supportedhighPeptides to Support Your GLP1 Health And Weight Loss Journey

Lactobacillus plantarum 299v enhances the body's absorption of non-heme iron.

"it's Lactobacillus is a there's a bacterial species, plantarum 299v. I think it's the other bacteria that helps your body absorb non-heme iron, too." (said at 0:24:10)

Multiple randomized clinical trials and a meta-analysis confirm that the probiotic strain Lactobacillus plantarum 299v (LP299V) significantly enhances the intestinal absorption of non-heme iron in humans. A 2019 meta-analysis of eight human studies found a statistically significant increase in iron absorption with Lp299v supplementation (pooled standardized mean difference 0.55, 95% CI 0.22–0.88), consistent with double-isotope tracer trials demonstrating improved non-heme iron bioavailability when consumed alongside meals or beverages.

0:29:06supportedvery lowPeptides to Support Your GLP1 Health And Weight Loss Journey

TUDCA indirectly increases endogenous GLP-1 production.

"Really a really interesting tidbit about TUDCA is it indirectly increases your own GLP-1 production anyway." (said at 0:29:06)

Preclinical evidence demonstrates that tauroursodeoxycholic acid (TUDCA) and related conjugated bile acids stimulate endogenous glucagon-like peptide-1 (GLP-1) secretion and production. In animal and cellular models, bile acids act on enteroendocrine L-cells primarily through activation of the membrane bile acid receptor TGR5 (and modulation of FXR pathways) to promote endogenous GLP-1 release. However, direct evidence in human clinical trials remains limited, so the certainty of the evidence is graded as very low.

0:29:10supportedhighPeptides to Support Your GLP1 Health And Weight Loss Journey

Dietary fat intake stimulates the release of bile from the gallbladder.

"And without the fat in the diet to trigger the bile release to absorb the fat, that's where you get the bile stasis and the gallbladder issues and potentially the stones too." (said at 0:29:10)

Dietary fat is the primary physiological stimulus for the release of cholecystokinin (CCK) from enteroendocrine cells in the small intestine, which stimulates gallbladder contraction and the expulsion of bile into the duodenum. In the absence of sufficient dietary fat (such as on extremely low-fat diets or during prolonged fasting), CCK release is blunted, leading to gallbladder hypomotility, biliary stasis, and an increased risk of cholesterol supersaturation and gallstone formation. In randomized clinical trials, very-low-fat diets (e.g., <2 g fat/day) caused impaired gallbladder emptying and significantly higher rates of gallstone development compared to diets containing modest amounts of dietary fat (e.g., 10 to 30 g/day), which maintained regular gallbladder emptying.

0:34:49supportedhighPeptides to Support Your GLP1 Health And Weight Loss Journey

Lipopolysaccharide (LPS) drives systemic inflammation and insulin resistance.

"and the LPS drives inflammation and then it drives the insulin resistance too" (said at 0:34:49)

Lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, is well established to trigger systemic inflammation and induce insulin resistance. Human experimental challenge trials using intravenous LPS infusion have demonstrated acute induction of systemic inflammatory responses followed by impaired glucose disposal and insulin resistance during hyperinsulinemic-euglycemic clamps. In animal models, continuous low-dose LPS infusion (metabolic endotoxemia) induces systemic and adipose tissue inflammation, hepatic steatosis, and insulin resistance via Toll-like receptor 4 (TLR4) signaling pathways.

0:39:32supportedhighPeptides to Support Your GLP1 Health And Weight Loss Journey

Caloric restriction and appetite reduction induced by GLP-1 agonists can lead to rapid muscle mass loss.

"caloric restriction, GLP-1s inducing caloric restriction and reduced appetite can cause rapid muscle mass loss, um, especially dosed at the wrong dose as we've established." (said at 0:39:32)

The claim is supported by clinical trial evidence and systematic reviews. GLP-1 receptor agonists (such as semaglutide and tirzepatide) induce appetite reduction and caloric restriction, which leads to significant weight loss accompanied by absolute lean mass and muscle mass loss. Meta-analyses of randomized controlled trials show that lean body mass loss accounts for approximately 15% to 25% (and up to 24.5% in some studies) of total weight lost during GLP-1 receptor agonist therapy, driven by the degree of caloric restriction and dosage (e.g., higher doses of semaglutide 2.4 mg and tirzepatide 15 mg resulting in greater absolute lean mass reductions).

0:43:23supportedhighPeptides to Support Your GLP1 Health And Weight Loss Journey

GBB (gamma-butyrobetaine) is the biochemical precursor to L-carnitine.

"There are other ingredients like GBB that you can use, which is the precursor to L-carnitine." (said at 0:43:23)

Gamma-butyrobetaine (GBB) is the direct biochemical precursor to L-carnitine in endogenous biosynthesis. In the final step of carnitine synthesis, the enzyme gamma-butyrobetaine hydroxylase/dioxygenase (BBOX or BBD) catalyzes the stereoselective hydroxylation of GBB to form L-carnitine.

0:43:29supportedhighPeptides to Support Your GLP1 Health And Weight Loss Journey

Carnitine and acetyl-L-carnitine are required in the mitochondria for fatty acid oxidation.

"And these are fantastic for lipolysis and fatty acid oxidation. They are required in the mitochondria to burn fat." (said at 0:43:29)

Carnitine is an obligate cofactor for mitochondrial long-chain fatty acid oxidation. Long-chain fatty acids cannot cross the inner mitochondrial membrane on their own and require the carnitine shuttle—comprising carnitine palmitoyltransferase I (CPT1), carnitine-acylcarnitine translocase (CACT), and carnitine palmitoyltransferase II (CPT2)—to enter the mitochondrial matrix for beta-oxidation.

0:44:12supportedhighPeptides to Support Your GLP1 Health And Weight Loss Journey

High levels of NAD clearance through NNMT consume methyl groups and reduce SAMe.

"and when NAD is cleared out of your body it also requires methyl groups um and SAMe to clear it out. So, a little side tangent, it's completely irrelevant to our point, but I really want to bring this up is when people are taking NAD therapy, they're doing infusions or NAD injections or really heavily loading up on NMN or NR for the purposes of increasing NAD, they never think about the back end of it. And if you've got a huge amount of NAD pooled, then you're also going to have an equally high amount of it clearing out through this NNMT enzyme, which is going to strip your methyl groups and reduce your SAMe" (said at 0:44:12)

The claim is supported by biochemical and mechanistic literature. Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide—the major clearance pathway for excess nicotinamide derived from NAD+ breakdown or high-dose NAD+ precursor supplementation—using S-adenosylmethionine (SAMe or SAM) as the methyl donor. Studies demonstrate that high NNMT activity consumes methyl groups from SAMe, reducing SAMe levels and lowering cellular methyl availability.

0:45:35supportedvery lowPeptides to Support Your GLP1 Health And Weight Loss Journey

JBSNF-000088 is a molecule that inhibits the NNMT enzyme.

"Um and there's another one called JBSNF-000088. Really terrible name for a peptide. No one's expected to remember it. I had to think pretty hard to remember what it's called, but that one also um inhibits that enzyme too." (said at 0:45:35)

Preclinical research demonstrates that JBSNF-000088 is a small-molecule analog of nicotinamide that inhibits nicotinamide N-methyltransferase (NNMT) activity and lowers 1-methyl-nicotinamide levels in cell and animal models. While the speaker referred to it in passing as a peptide, chemically it is a small molecule inhibitor/substrate analog.

0:48:58supportedhighPeptides to Support Your GLP1 Health And Weight Loss Journey

1-Methylnicotinamide (1-MNA) is the breakdown clearance byproduct of NAD metabolism.

"It's 1-methylnicotinic acid or 1-MNA. We don't sell that, but that is what um NAD breaks down to and is cleared to." (said at 0:48:58)

1-Methylnicotinamide (1-MNA, also abbreviated MNAM) is the methylated clearance byproduct of nicotinamide, which is generated when NAD+ is consumed and broken down by NAD-dependent enzymes (such as sirtuins, PARPs, and CD38). Nicotinamide N-methyltransferase (NNMT) transfers a methyl group from S-adenosyl-L-methionine (SAM) to nicotinamide, producing 1-MNA, which is subsequently excreted primarily in urine. While the speaker momentarily misnamed it '1-methylnicotinic acid' (which chemically refers to trigonelline), the characterization of 1-MNA as the clearance and breakdown product of NAD metabolism is biochemically accurate.

0:49:24supportedlowPeptides to Support Your GLP1 Health And Weight Loss Journey

Apigenin, fisetin, and quercetin inhibit the enzyme CD38 (NADase).

"Um, yeah, the other ingredients in that product that really allow it to work well are apigenin, fisetin, and um quercetin. And these inhibit an enzyme called CD38 or NADase. That's an enzyme that breaks down NAD as well." (said at 0:49:24)

Preclinical biochemical and animal studies demonstrate that apigenin, quercetin, and related flavonoids inhibit CD38, an enzyme that acts as a major NADase degrading intracellular NAD+. In vitro assays and rodent studies show that pharmacological inhibition of CD38 by these flavonoids elevates NAD+ levels and promotes sirtuin-mediated pathways.

0:55:50supportedhighPeptides to Support Your GLP1 Health And Weight Loss Journey

Caffeine exerts its physiological effects by acting on adenosine receptors.

"caffeine has receptors, adenosine receptors, which it acts on." (said at 0:55:50)

The primary mechanism of action for caffeine at typical physiological concentrations is competitive antagonism of adenosine receptors (predominantly A1 and A2A subtypes). This blockade prevents adenosine-mediated inhibitory signaling, leading to increased central nervous system arousal, heightened neurotransmitter release, and enhanced neuromuscular performance.

1:00:10supportedhighPeptides to Support Your GLP1 Health And Weight Loss Journey

Palmitoylethanolamide (PEA) stabilizes mast cells, is present in human breast milk, and possesses analgesic and anti-inflammatory properties.

"It's in our histamine product because it stabilizes mast cells. It's found in breast milk. It's, you know, mothers who are breastfeeding will give PEA to their to their child or their newborn and it's an analgesic and a pain reliever and an anti-inflammatory." (said at 1:00:10)

The claim that palmitoylethanolamide (PEA) is present in human breast milk and possesses analgesic and anti-inflammatory properties is supported by clinical and observational evidence. Analytical studies of human milk confirm that endogenous N-acylethanolamines, including PEA, are naturally present in mother's milk. Furthermore, multiple systematic reviews and meta-analyses of double-blind randomized controlled trials demonstrate that oral PEA effectively reduces chronic, neuropathic, and inflammatory pain compared to inactive controls, while modulating immune and inflammatory responses.

1:00:48supportedmoderatePeptides to Support Your GLP1 Health And Weight Loss Journey

Curcumin can bind/sequester iron and impair iron absorption in individuals with low iron levels.

"because curcumin can, you know, sequester iron and have some issues with iron absorption for those who are low." (said at 1:00:48)

In vitro and in vivo animal studies demonstrate that curcumin is an active iron chelator that binds ferric iron in the gastrointestinal tract and can precipitate or worsen iron deficiency, particularly against a backdrop of marginal iron intake or subclinical deficiency. Human case reports have similarly documented reversible iron deficiency anemia associated with high-dose turmeric supplementation due to impaired intestinal iron absorption.

1:01:25supportedhighPeptides to Support Your GLP1 Health And Weight Loss Journey

Palmitoylethanolamide (PEA) relieves pain and reduces inflammation following an injury.

"Say you got an injury, the PEA will on the front end give you the pain relief and help with the inflammation while the peptide works on all the all the growth factors and um accelerating the healing process." (said at 1:01:25)

A systematic review and meta-analysis of randomized controlled trials (PMID: 39798151) evaluated palmitoylethanolamide (PEA) across various pain conditions and confirmed that PEA significantly reduces pain across nociceptive, neuropathic, and nociplastic pain types. Additionally, randomized clinical trials demonstrate that PEA reduces inflammatory markers (such as TNF-α, IL-1β, IL-6, and CRP) and provides pain relief in inflammatory joint conditions (PMID: 37767025, PMID: 22558609). While PEA has shown mixed results specifically for post-exercise acute muscle damage (PMID: 39086058, PMID: 32106527), its broader pain-relieving and anti-inflammatory properties are well-supported by high-level clinical evidence.

1:03:22supportedvery lowPeptides to Support Your GLP1 Health And Weight Loss Journey

The peptide KPV reduces interleukin-6 and TNF-alpha in the gut, which are inflammatory cytokines driving gut inflammation and permeability.

"It works on the gut to reduce the interleukin-6 and TNF-alpha which are some of the inflammatory cytokines that drive gut inflammation and permeability." (said at 1:03:22)

Preclinical in vitro and animal studies demonstrate that the tripeptide KPV (Lys-Pro-Val, derived from alpha-melanocyte-stimulating hormone) is transported into intestinal epithelial and immune cells via the PepT1 transporter. In these rodent models of colitis (such as DSS- and TNBS-induced intestinal inflammation), KPV inhibits NF-κB signaling, downregulates key proinflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and promotes the recovery of the colonic mucosal barrier. However, evidence is currently limited to cellular and animal models, with no completed clinical trials evaluating these effects in humans.

1:03:50supportedmoderatePeptides to Support Your GLP1 Health And Weight Loss Journey

Lipopolysaccharide (LPS) leaking from the gut causes liver issues and impairs insulin signaling and drives inflammation.

"to reduce the LPS that's going to cause the liver issues and um you know help and um potentially cause issues with uh insulin signaling and inflammation." (said at 1:03:50)

The claim is supported. Translocation of bacterial lipopolysaccharide (LPS) across an impaired intestinal barrier into the portal and systemic circulation (metabolic endotoxemia) is a recognized driver of chronic low-grade inflammation, impaired hepatocyte and peripheral insulin signaling (e.g., through disruption of IRS1/2 insulin receptor association), and liver pathology including metabolic dysfunction-associated steatotic liver disease (MASLD).

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