HoldsUp

Dr. Tyna Moore · 2025-10-31 · Tyna Moore (host), Kyal Van Der Leest

Peptides to Support Your GLP1 Health And Weight Loss Journey | Kyal Van Der Leest of LVLUP EP. 236

43 research-tied claims examined: 4 contradicted 7 overstated 2 context 30 supported

4

Contradicted by research

0:05:30Tyna Moore (host)contradictedmoderate

GLP-1 receptor agonists ramp up AMPK, which can cause muscle wasting in people who do not consume adequate protein.

"Number two is wasting. Even if you're strength training, there is still this ramping up of AMPK, and it can lead to wasting in folks that are not consuming enough protein or not actually doing anything to mitigate or protect their muscle." (said at 0:05:30)

The speaker's claim bundles a known clinical phenomenon with an incorrect mechanistic claim. While clinical trials and systematic reviews confirm that glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy is accompanied by reductions in lean body mass—typically accounting for 25% to 30% of total weight loss during caloric restriction—this loss is primarily a consequence of hypocaloric weight reduction rather than AMPK-induced muscle proteolysis. In mechanistic and preclinical literature, GLP-1 RA–induced activation of AMP-activated protein kinase (AMPK) is actually associated with muscle protection, promoting mitochondrial biogenesis, suppressing inflammatory pathways, and decreasing the expression of proteolytic markers (such as MuRF1 and MAFbx), rather than causing muscle wasting.

0:43:56Kyal Van Der Leestcontradictedvery low

5-Amino-1MQ inhibits nicotinamide N-methyltransferase (NNMT), which preserves NAD levels.

"Its mechanistic way that it works is by inhibiting NNMT, which is the main enzyme that actually clears NAD out of your body into um nicotinic acid. So if you the 5-Amino inhibits that enzyme's function and basically preserves your NAD levels" (said at 0:43:56)

The speaker bundles two claims with an inaccurate biochemical mechanism: (1) 5-amino-1MQ is a small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT), which is supported in preclinical cell and animal studies; (2) NNMT functions by converting NAD into nicotinic acid to clear it from the body, which is contradicted by established biochemistry. NNMT does not metabolize NAD into nicotinic acid; rather, it transfers a methyl group from S-adenosylmethionine (SAM) to nicotinamide (NAM)—a product of NAD degradation and precursor in the NAD salvage pathway—generating 1-methylnicotinamide (MNA). By inhibiting NNMT, 5-amino-1MQ prevents the clearance of nicotinamide as MNA, allowing more nicotinamide to be salvaged back into NAD+. While NNMT inhibition by 5-amino-1MQ has been shown to support NAD+ levels in preclinical models, the stated mechanism of NAD conversion into nicotinic acid is incorrect, and clinical trial evidence in humans is lacking.

0:52:16Kyal Van Der Leestcontradictedlow

DNF-10 is a peptide ingredient that increases neuropeptide Y.

"I used peptides that increase neuropeptide Y. There's one called DNF-10." (said at 0:52:16)

DNF-10 is a commercial yeast hydrolysate (Saccharomyces cerevisiae hydrolysate below 10 kDa) marketed as an appetite suppressant and anti-obesity ingredient. Neuropeptide Y (NPY) is a potent orexigenic (appetite-stimulating) neuropeptide. Rather than increasing NPY, published studies examining low-molecular-weight yeast hydrolysates (<10 kDa) show that they decrease or downregulate NPY expression in hypothalamic appetite-regulating centers (such as the paraventricular nucleus and lateral hypothalamic area) to reduce food intake and body weight gain. The speaker inverted the claimed mechanism of action.

1:03:02Kyal Van Der Leestcontradictedlow

The peptide KPV is used as part of the Ritchie Shoemaker protocol to increase alpha-melanocyte-stimulating hormone (alpha-MSH) in cases of mold exposure and Chronic Inflammatory Response Syndrome (CIRS).

"It's part of the Ritchie Shoemaker protocol for increasing alpha-MSH. So that's why I love it for, you know, mold injury and CIRS uh not mold injury, mold exposure and CIRS" (said at 1:03:02)

The claim misidentifies both the biochemical nature of KPV and its therapeutic function. KPV (lysine-proline-valine) is the C-terminal tripeptide fragment of alpha-melanocyte-stimulating hormone (alpha-MSH) itself, not a molecule that stimulates or increases endogenous alpha-MSH levels. While KPV is studied in pre-clinical research for retaining some of the anti-inflammatory properties of alpha-MSH without causing pigmentation, published descriptions of the Ritchie Shoemaker protocol for Chronic Inflammatory Response Syndrome (CIRS) do not include KPV as an intervention to raise alpha-MSH. Published CIRS literature focuses on clearing sinonasal MARCoNS colonization, toxin binders, and vasoactive intestinal polypeptide (VIP).

7

Overstated

0:17:54Tyna Moore (host)overstatedlow

Small intestinal bacterial overgrowth (SIBO) drives insulin resistance and obesity.

"SIBO will drive, it's not a direct cause, but it will drive insulin resistance and obesity. I think it is one of the root causes of insulin resistance and obesity, especially in this country, in the US." (said at 0:17:54)

While clinical literature documents an observational association between small intestinal bacterial overgrowth (SIBO), pediatric/adult obesity, and related metabolic conditions (such as metabolic dysfunction-associated steatotic liver disease and insulin resistance), claiming that SIBO 'drives' obesity and insulin resistance as a 'root cause' overstates the scientific evidence. Systematic reviews and mechanistic evaluations emphasize that current evidence is predominantly correlational and cross-sectional; causality has not been demonstrated, and obesity or altered GI motility may just as likely predispose individuals to SIBO.

0:52:46Kyal Van Der Leestoverstatedlow

Dihydroberberine is approximately 40 times more bioavailable/absorbable than standard berberine.

"But dihydroberberine is about 40 times more absorbable than regular berberine. So that's going to work better for, you know, systemic glucose control" (said at 0:52:46)

The claim that dihydroberberine (DHB) is approximately 40 times more bioavailable/absorbable than standard berberine (BBR) is overstated. Clinical trial data in humans demonstrate that oral ingestion of dihydroberberine produces higher plasma berberine AUC (area under the curve) and Cmax compared to standard berberine, but at a magnitude of approximately 5-fold (for a 100 mg dose of DHB vs. a 500 mg dose of BBR, resulting in about a 5-fold to 6-fold increase in blood concentration relative to dose), rather than 40-fold. Additionally, transdermal administration of DHB in rats showed increased relative absorption compared to oral BBR, but no human or animal pharmacokinetic study demonstrates a 40-fold absorption advantage for oral dihydroberberine over oral berberine.

0:54:26Kyal Van Der Leestoverstatedvery low

BPC-157 upregulates growth hormone receptor density.

"BPC has an effect on upregulating growth hormone receptor density, which means that you know, anyone who's doing any training, growth hormone is going to work a lot better and you're going to recover faster and preserve your muscle um a lot better from that one." (said at 0:54:26)

Evidence that BPC-157 upregulates growth hormone receptor expression comes strictly from preclinical laboratory models, primarily an in vitro study on isolated rat Achilles tendon fibroblasts showing dose- and time-dependent increases in growth hormone receptor mRNA and protein levels. There is no clinical trial data in humans demonstrating that BPC-157 increases growth hormone receptor density in vivo or that it enhances muscle preservation, recovery, or training adaptations in athletes.

0:58:01Kyal Van Der Leestoverstatedvery low

BPC-157 upregulates VEGF and promotes angiogenesis (new blood vessel formation).

"Angiogenesis is one of the pathways that BPC upregulates. VEGF, angiogenesis, new blood vessel formation. That's fantastic for injury recovery for regeneration." (said at 0:58:01)

Preclinical evidence from animal models and cell cultures demonstrates that pentadecapeptide BPC-157 promotes angiogenesis (new blood vessel formation) and upregulates vascular endothelial growth factor (VEGF) and its receptor VEGFR2 during tissue healing (such as in injured tendons, muscles, and burn wounds). However, asserting this as a proven therapy for injury recovery in humans overstates the evidence, as all published data on BPC-157's angiogenic properties are derived strictly from in vitro assays and animal studies; no human clinical trials have established these effects or confirmed safety and efficacy in patients.

1:01:45Kyal Van Der Leestoverstatedvery low

BPC accelerates injury recovery and connective tissue healing by acting on growth factors.

"the peptide works on all the all the growth factors and um accelerating the healing process. So that product is awesome for you know uh connective tissue injuries and helping with injury recovery." (said at 1:01:45)

Preclinical studies (primarily in vitro and rodent models) indicate that body protection compound-157 (BPC-157) modulates growth factors (such as VEGF, EGF, and growth hormone receptor expression) and can promote tendon, ligament, and muscle healing. However, claiming that it works on all growth factors and definitively accelerates connective tissue injury recovery in humans overstates the evidence. Systematic reviews emphasize that human clinical trials evaluating its efficacy and safety in musculoskeletal and connective tissue repair are currently lacking.

1:03:38Kyal Van Der Leestoverstatedvery low

BPC-157 can help preserve muscle mass while sealing the gut barrier to reduce lipopolysaccharide (LPS) leakage.

"The BPC's in it that's going to help preserve that could help preserve the muscle mass whilst it's sealing up the gut to reduce the LPS that's going to cause the liver issues" (said at 1:03:38)

The claim states that BPC-157 helps preserve muscle mass while sealing the gut barrier to reduce lipopolysaccharide (LPS) leakage. While BPC-157 has shown gastroprotective, mucosal healing, and muscle regenerative properties in animal models (such as rats subjected to transections, crush injuries, fistulas, and cachexia models), virtually all data supporting these mechanisms are derived from preclinical rodent studies. Systematic and scoping reviews confirm that there is an absence of robust randomized controlled clinical trials in humans evaluating muscle preservation or gut barrier restoration. Presenting these therapeutic effects as established human benefits overstates the existing evidence base.

1:04:26Tyna Moore (host)overstatedvery low

5-Amino-1MQ produces a thermogenic effect.

"and I love the Longevity for what you all the reasons you said, but that 5-Amino-1MQ just kind of has that thermogenic effect as well." (said at 1:04:26)

5-Amino-1MQ (5-amino-1-methylquinolinium) is an experimental small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT). Preclinical studies in diet-induced obese mice and cultured adipocytes have shown that NNMT inhibition reduces adipose tissue mass, suppresses lipogenesis, and increases cellular energy expenditure without altering food intake. However, no human clinical trials evaluating 5-Amino-1MQ or other NNMT inhibitors for thermogenesis, metabolic rate, or weight loss have been published. Claiming a thermogenic effect in humans overstates evidence that is strictly limited to animal and cell models.

2

Needs context

0:46:35Kyal Van Der Leestneeds contextvery low

SLU-PP-332 functions as an exercise mimetic by acting as an agonist at the estrogen receptor-related receptor alpha.

"like another one that's quite trending at the moment that I'm a little hesitant to talk about because it has some potential side effects, but it's called SLU-PP-332. This is another small molecule. It's not a peptide, but it's clumped into them. Um, this works via that estrogen receptor alpha agonism, and they call it exercise in a pill." (said at 0:46:35)

SLU-PP-332 is a synthetic pan-agonist of the estrogen-related receptors (ERRs) with highest potency for ERRα, and has demonstrated exercise-mimetic effects (such as enhanced mitochondrial respiration, increased type IIa oxidative muscle fibers, and improved endurance) in rodent models and cell culture. However, two important qualifications apply: first, the speaker conflated the orphan nuclear receptor 'estrogen-related receptor alpha' (ERRα) with the classical 'estrogen receptor alpha' (ERα), which are distinct receptor systems; second, evidence for SLU-PP-332's exercise-mimetic effects is currently limited entirely to preclinical animal and in vitro studies, with no completed human trials.

0:54:48Kyal Van Der Leestneeds contextmoderate

Thymosin beta-4 (TB4) fragments interact with actin to help preserve actin in muscle tissue.

"And TB4 fragments also have an effect on actin, which is one of the main um uh proteins in muscle fiber and it helps preserve actin too." (said at 0:54:48)

Thymosin beta-4 (Tβ4) and its actin-binding peptide fragments bind globular monomeric actin (G-actin), which is a principal structural protein in muscle fibers. In cellular physiology, Tβ4 functions primarily as an actin monomer-sequestering peptide, maintaining an unpolymerized G-actin pool and regulating actin filament assembly, sarcomere dynamics, and muscle tissue repair. Describing this biochemical buffering and sequestration mechanism as 'preserving actin' conveys the general role of Tβ4 in maintaining the intracellular actin pool, though its primary biochemical function is the regulation of actin polymerization dynamics rather than passive tissue preservation.

30

Supported by research

0:03:33Tyna Moore (host)supportedhigh

The highest available standard dose of semaglutide is 2.4 milligrams.

"the dose of semaglutide is 2.4 milligrams. That's the highest dose you can get. The very highest dose." (said at 0:03:33)

Subcutaneous semaglutide for chronic weight management is evaluated and administered at a standard maximum maintenance dose of 2.4 mg once weekly. In large-scale phase 3 randomized controlled trials of the STEP program evaluating semaglutide in adults with overweight or obesity, 2.4 mg weekly represents the targeted full maintenance dose.

0:05:00Tyna Moore (host)supportedlow

Recent studies and clinical data show that GLP-1 receptor agonist use can lead to small intestinal bacterial overgrowth (SIBO).

"Number one, we have data showing, and in recent studies show, and I've seen this even with true microdoses, SIBO setting in, which is small intestinal bacterial overgrowth." (said at 0:05:00)

Recent clinical data support an association between glucagon-like peptide-1 receptor agonist (GLP-1 RA) use and an increased risk of small intestinal bacterial overgrowth (SIBO), likely related to GLP-1-induced delays in gastrointestinal motility. A large 2025 global multicenter retrospective cohort study evaluating 216,173 propensity-score-matched pairs of adult type 2 diabetes patients found a significantly higher incidence of diagnostically confirmed SIBO in patients receiving GLP-1 RAs or dual GLP-1/GIP agonists compared to other second-line diabetes medications in short-term follow-up (HR 2.14, 95% CI 1.13–4.07). The certainty of evidence is graded as low due to the retrospective observational design.

0:08:35Kyal Van Der Leestsupportedhigh

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.

0:10:10Kyal Van Der Leestsupportedmoderate

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.

0:16:22Tyna Moore (host)supportedhigh

GLP-1 binds directly to receptors on immune cells.

"because it sits on the m- they it actually binds our immune cells. GLP-1 does." (said at 0:16:22)

Glucagon-like peptide-1 (GLP-1) binds directly to GLP-1 receptors (GLP-1R) expressed on various immune cells, including T cell subsets and intraepithelial lymphocytes. Multiple studies demonstrate direct GLP-1R expression and functional receptor binding in peripheral blood regulatory T cells (Tregs), intestinal intraepithelial lymphocytes (IELs), and other immune populations, mediating anti-inflammatory and immunomodulatory responses.

0:21:45Kyal Van Der Leestsupportedhigh

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.

0:24:10Kyal Van Der Leestsupportedhigh

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.

0:25:30Tyna Moore (host)supportedmoderate

Oral iron supplementation can nourish pathogenic bacteria and increase intestinal lipopolysaccharide (LPS) production.

"And then on top of it, iron orally feeds the bad bugs. So if you've got SIBO and then you've got bugs in there from the slowed gastrointestinal motility that are creating a lot of lipopolysaccharides and that LPS is driving the histamine issue" (said at 0:25:30)

Published literature confirms that unabsorbed oral iron reaches the colon and promotes the proliferation and virulence of iron-dependent Gram-negative enteropathogens (such as members of the Enterobacteriaceae family, including Escherichia coli and Salmonella spp.), which are primary producers of lipopolysaccharide (LPS) / endotoxin. Concurrently, oral iron supplementation frequently suppresses beneficial commensal taxa such as Bifidobacterium and Lactobacillus, leading to gut dysbiosis and increased inflammatory potential.

0:29:06Kyal Van Der Leestsupportedvery low

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.

0:23:55Kyal Van Der Leestsupportedhigh

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).

0:23:01Kyal Van Der Leestsupportedmoderate

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.

0:29:10Kyal Van Der Leestsupportedhigh

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.

0:27:02Tyna Moore (host)supportedhigh

Gallstones can lodge in the pancreatic duct or biliary tract and cause pancreatitis.

"the concern about gallstones and the gallstone potentially lodging itself into the pancreas and ending up with pancreatitis, which is just a complete nightmare." (said at 0:27:02)

Gallstones are well established as the primary cause of acute pancreatitis (gallstone pancreatitis), accounting for approximately 50% of all cases. This occurs when gallstones migrate from the gallbladder through the biliary tract and obstruct the distal common bile duct, the ampulla of Vater, or the pancreatic duct, triggering pancreatic inflammation.

0:31:44Tyna Moore (host)supportedmoderate

GLP-1 receptor agonists have anti-inflammatory effects on joints and the brain.

"and they have such a phenomenal anti-inflammatory effect on the joints and the brain, and people and we have studies on this" (said at 0:31:44)

Extensive preclinical and clinical evidence demonstrates that glucagon-like peptide-1 receptor agonists (GLP-1RAs) exert anti-inflammatory effects across multiple tissues, including the central nervous system and joint structures. In the brain, GLP-1RAs suppress microglial activation, inhibit the NLRP3 inflammasome, and reduce neuroinflammation. In the joints, in vitro, preclinical in vivo, and clinical studies in conditions like osteoarthritis and rheumatoid arthritis show weight-loss-dependent and weight-loss-independent anti-inflammatory and chondroprotective actions.

0:32:58Tyna Moore (host)supportedlow

Lipopolysaccharides (LPS) drive pain through interactions with the central nervous system.

"Because the bad bugs produce these toxins, and these toxins will drive pain. And it it's a whole thing it does with your central nervous system." (said at 0:32:58)

Preclinical and mechanistic literature supports the concept that bacterial lipopolysaccharide (LPS)—an endotoxin produced by Gram-negative bacteria—promotes pain hypersensitivity and central sensitization through interactions with the central nervous system. LPS binds Toll-like receptor 4 (TLR4) complexes on glial cells (such as microglia and astrocytes) and neurons within the spinal cord and brain, inducing neuroinflammatory signaling cascades, cytokine release, and central sensitization that drive hyperalgesia and chronic pain states. Evidence is largely derived from rodent and in vitro neuroinflammatory models.

0:34:49Kyal Van Der Leestsupportedhigh

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.

0:39:32Kyal Van Der Leestsupportedhigh

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).

0:43:23Kyal Van Der Leestsupportedhigh

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.

0:43:29Kyal Van Der Leestsupportedhigh

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.

0:44:12Kyal Van Der Leestsupportedhigh

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.

0:45:35Kyal Van Der Leestsupportedvery low

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.

0:48:58Kyal Van Der Leestsupportedhigh

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.

0:49:24Kyal Van Der Leestsupportedlow

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.

1:00:10Kyal Van Der Leestsupportedhigh

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.

1:00:48Kyal Van Der Leestsupportedmoderate

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.

0:55:50Kyal Van Der Leestsupportedhigh

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.

1:01:25Kyal Van Der Leestsupportedhigh

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.

1:02:26Tyna Moore (host)supportedmoderate

Palmitoylethanolamide (PEA) helps with histamine issues.

"And you're right with the again with that histamine issue. You have a histamine product, but PEA is so good for histamine as well." (said at 1:02:26)

Palmitoylethanolamide (PEA) acts as an autacoid local inflammation antagonist (ALIAmide) that downregulates mast cell degranulation and inhibits histamine release. In preclinical models (including isolated mast cells and skin organ cultures), PEA significantly inhibits immunologically triggered histamine release. In a double-blind, randomized, placebo-controlled trial of individuals with allergic rhinitis (a classic histamine-mediated condition), supplementation with 350 mg/day of PEA led to a significant reduction in circulating histamine levels alongside improvements in allergic symptom scores in symptomatic participants.

1:03:22Kyal Van Der Leestsupportedvery low

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.

1:03:50Kyal Van Der Leestsupportedmoderate

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).

Unverified means no publication matching the claim was located; it does not prove the claim false. Spotted an error? See the corrections policy - disputes from the people quoted are prioritized.