HoldsUp

John Gilday

Mara Labs

John Gilday is associated with Mara Labs and has a research background in organic chemistry. His peer-reviewed publications focus on synthetic organic chemistry, including asymmetric synthesis, organolithium-mediated reactions, and the chemical synthesis of nitrogen-containing heterocycles such as aziridines, piperidines, and sparteine derivatives.

26 claims checked on air: 1 context 4 contradicted 6 overstated 11 supported 4 unverified

What they said on air - overstated

0:04:15overstatedmoderateStop the "Toxic" Estrogen Loop: The Secret to Safer HRT

Up to menopause women are protected against cardiometabolic conditions and fatty liver, but after menopause disease rates accelerate and catch up to men around age 60.

"as um up to menopause a woman is protected against all kinds of disease states, you know, including all cardiometabolic states, fatty liver, just the list goes on and on. And then as you go through menopause, a woman actually catches back up to a man, and so the rate actually accelerates faster than a man as as you lose estrogen and catches back up, you know, close to around 60." (said at 0:04:15)

The speaker accurately describes the sex-specific trajectory of cardiometabolic risk and nonalcoholic fatty liver disease (NAFLD): premenopausal women exhibit relative protection compared to men due to estrogen-mediated effects on fat partitioning and vascular health, followed by accelerated accumulation of visceral adiposity and metabolic risk post-menopause that narrows the gap with men around age 60. However, claiming that premenopausal women are protected against 'all kinds of disease states' and 'all cardiometabolic states' overstates the level of protection, as premenopausal women can and do develop cardiometabolic disorders and liver disease.

0:37:20overstatedmoderateStop the "Toxic" Estrogen Loop: The Secret to Safer HRT

Direct antioxidants like vitamin A, vitamin C, and vitamin E have been shown to block the exercise stimulus that leads to strength gains.

"So, all the all the ones that have been shown to block exercise um uh were that you know, the stimulus that makes you get stronger are like vitamin E, vitamin A, vitamin C, you know, the direct antioxidants." (said at 0:37:20)

While high-dose antioxidant supplementation (particularly vitamins C and E) has been shown in some studies to dampen acute redox-sensitive intracellular signaling pathways and selectively attenuate certain muscular hypertrophy metrics, meta-analyses and randomized controlled trials show that they do not consistently block or attenuate gains in muscle strength. A 2020 systematic review and meta-analysis of randomized controlled trials (PMID 31851538) found no significant negative effect of vitamin C and/or E supplementation on muscle strength or lean mass gains following resistance training. In individual trials, such as Bjørnsen et al. (PMID 26129928), maximal strength (1RM) improved significantly and similarly in both antioxidant and placebo groups despite minor differences in lean mass gains. Furthermore, evidence specifically demonstrating that vitamin A blocks strength adaptations is lacking.

0:47:48overstatedlowStop the "Toxic" Estrogen Loop: The Secret to Safer HRT

Sulforaphane exerts protective antimicrobial effects against Helicobacter pylori and small intestinal bacterial overgrowth (SIBO).

"it's actually protective for bacteria in your stomach like H H. pylori. It's protective of SIBO. Um if you get high doses released right into your um small intestines, it would be protective." (said at 0:47:48)

The speaker overstates the evidence by asserting that sulforaphane is protective against small intestinal bacterial overgrowth (SIBO) and that high doses released into the small intestine are protective, while claiming antimicrobial protection against Helicobacter pylori. For Helicobacter pylori, in vitro and preclinical studies show direct antibacterial activity, and clinical trials demonstrate that sulforaphane-rich broccoli sprout consumption reduces H. pylori colonization markers and attenuates gastric inflammation (PMID 19349290, PMID 39741515). However, human clinical trials show that sulforaphane does not reliably eradicate H. pylori when given alone (PMID 25287166) or improve eradication rates when added to standard clarithromycin-based triple therapy (PMID 31830776). For SIBO, there is no published clinical or preclinical evidence evaluating sulforaphane as a treatment or protective agent against SIBO. A systematic review of sulforaphane's antibacterial effects notes protection against aspirin-induced small intestinal damage in preclinical models, but does not identify evidence for SIBO (PMID 40553560). No published record matching sulforaphane for SIBO was located.

0:47:48overstatedmoderateStop the "Toxic" Estrogen Loop: The Secret to Safer HRT

The majority of the conversion of glucoraphanin to sulforaphane is performed by gut bacteria in the colon.

"the precursor, majority of the conversion happens by bacteria in your colon" (said at 0:47:48)

The claim that the majority of glucoraphanin conversion to sulforaphane occurs via gut bacteria in the colon is overstated. In fresh cruciferous vegetables, the plant enzyme myrosinase rapidly converts glucoraphanin to sulforaphane upon chewing and upper gastrointestinal digestion, providing approximately 3- to 10-fold higher bioavailability than microbial conversion. Mammalian host cells lack myrosinase-like activity, so when plant myrosinase is inactivated by cooking, blanching, or in isolated glucoraphanin supplements, conversion does rely on colonic microbiota; however, microbial conversion is relatively inefficient (bioavailability typically around 10–20%), meaning most ingested glucoraphanin remains unconverted or is metabolized into other compounds.

0:56:25overstatedvery lowStop the "Toxic" Estrogen Loop: The Secret to Safer HRT

Sulforaphane directly conjugates and inhibits STAT3 dimerization.

"I was going to start talking about STAT3. That's a new thing that that I found out it directly conjugates and and inhibits STAT3, which is in the center of inflammation in in tons of ways. And I was looking for, you know, a supplement to try and um work on, you know, the dimerization of STAT3. And it turns out sulforaphane is the best at that." (said at 0:56:25)

Preclinical cell culture studies show that sulforaphane can suppress STAT3 activation and phosphorylation (typically secondary to upstream kinases such as JAK2/Src, ROS modulation, or interactions with regulatory partners like PKM2). However, published literature does not demonstrate that sulforaphane directly conjugates to STAT3 to block its dimerization, nor is there comparative clinical evidence establishing sulforaphane as the 'best' supplement for targeting STAT3 dimerization. All existing evidence for sulforaphane's effects on STAT3 signaling is limited to preliminary in vitro and animal models.

1:20:23overstatedlowStop the "Toxic" Estrogen Loop: The Secret to Safer HRT

A large number of the side effects and symptoms of menopause are caused by the loss of estrogen receptor beta (ERβ) activation.

"a large number of the side effects from menopause are are because of the loss of estrogen receptor beta activation." (said at 1:20:23)

While estrogen receptor beta (ERβ) is actively researched as a target for selective therapies to alleviate menopausal symptoms (such as hot flashes and memory dysfunction) without the cancer risks driven by estrogen receptor alpha (ERα) activation, claiming that a "large number of the side effects from menopause are because of the loss of estrogen receptor beta activation" overstates the evidence. Both ERα and ERβ mediate estrogenic signaling, and animal models indicate that activation of either receptor (or predominantly ERα in classical pathways) can regulate thermoregulation and other physiological symptoms. Selective ERβ agonists (e.g., MF101/Menerba, EGX358) are being developed for therapeutic symptom relief, but menopausal symptoms stem broadly from systemic loss of circulating 17β-estradiol acting across both ERα and ERβ, as well as non-genomic estrogen pathways.

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