HoldsUp

Dr. Tyna Moore · 2026-01-23 · Tyna Moore (host), Tyler Panzner

Why Supplements Make Some Women Feel Worse (And What Actually Works) | Dr Tyler Panzner Ep 245

35 research-tied claims examined: 4 contradicted 8 overstated 22 supported 1 unverified

22

Supported by research

0:03:14Tyler Panznersupportedmoderate

Low vitamin D is linked to autoimmunity, inflammation, and mental health conditions.

"We know that low vitamin D is linked to autoimmunity, inflammation, mental health conditions, you name it." (said at 0:03:14)

Extensive epidemiological and systematic review evidence demonstrates that low vitamin D status is consistently associated with autoimmune diseases, systemic inflammation, and mental health conditions (particularly depressive disorders). Meta-analyses of prospective and observational studies show increased risk of depression (odds ratio 1.45) and lower serum vitamin D concentrations in individuals with autoimmune disorders such as systemic lupus erythematosus and multiple sclerosis, alongside inverse relationships with inflammatory markers. While observational associations are robust, randomized trials investigating whether vitamin D supplementation causally reverses or prevents these conditions have yielded more mixed results.

0:03:40Tyler Panznersupportedmoderate

Vitamin D receptor signaling stimulates brain cells to synthesize dopamine and serotonin.

"if it's a brain cell, it'll tell it to make more dopamine, make more serotonin. This is why seasonal depression exists." (said at 0:03:40)

Preclinical in vitro and in vivo studies demonstrate that active vitamin D (calcitriol) binds the vitamin D receptor (VDR) to stimulate the expression of the rate-limiting enzymes for both serotonin and dopamine synthesis in neuronal cells. Specifically, calcitriol upregulates tryptophan hydroxylase 2 (TPH2) transcription in brain cells via functional vitamin D response elements (VDREs) to enhance serotonin synthesis, and increases tyrosine hydroxylase (TH) expression to promote dopamine synthesis.

0:03:50Tyler Panznersupportedmoderate

Vitamin D binding to immune cells shifts them away from a pro-inflammatory state.

"If it binds to an immune cell, it can quiet it down and shift away from a pro-inflammatory state." (said at 0:03:50)

The active form of vitamin D (1,25-dihydroxyvitamin D) binds to vitamin D receptors (VDR) present on numerous immune cell types (including T lymphocytes, B lymphocytes, macrophages, and dendritic cells). Activation of VDR signaling suppresses pro-inflammatory cytokine expression (such as IFN-gamma, IL-6, TNF-alpha, and IL-17) while promoting anti-inflammatory cytokine production (such as IL-10) and driving differentiation toward anti-inflammatory cell phenotypes (such as regulatory T cells and M2 macrophages).

0:03:56Tyler Panznersupportedmoderate

Vitamin D binding to osteoblasts stimulates bone formation.

"If it's an osteoblast or a bone cell, it stimulates the formation of bone. This is why it's linked to osteoporosis." (said at 0:03:56)

Active vitamin D (1α,25-dihydroxyvitamin D3) acts directly on bone cells through the vitamin D receptor (VDR) present in osteoblasts. Signaling via the VDR in osteoblasts regulates their differentiation into mature, bone-matrix-producing cells and controls extracellular matrix mineralization. In vitro and in vivo models confirm that vitamin D promotes osteoblast differentiation, stimulates the expression of bone matrix proteins, and facilitates bone formation and mineralization, which underpins its direct biological connection to bone density regulation and osteoporosis.

0:11:43Tyler Panznersupportedmoderate

Sleep deprivation increases the density of serotonin 2A (5-HT2A) receptors on the surface of the brain.

"sleep deprivation increases the amount of the serotonin 2A receptor on the surface of the brain. So that's actually the receptor that classical psychedelics bind to" (said at 0:11:43)

Human neuroimaging and animal studies show that acute sleep deprivation increases serotonin 2A (5-HT2A) receptor density and binding in the cerebral cortex. A PET imaging study in 18 healthy volunteers found that 24 hours of total sleep deprivation resulted in a 9.6% increase in neocortical [18F]altanserin binding at 5-HT2A receptors, with significant increases across several cortical areas including the frontal and parietal cortices. Rodent studies also demonstrate that 6 to 8 hours of sleep deprivation rapidly upregulates 5-HT2A receptor mRNA and protein levels in the frontal cortex via the transcription factor Egr3.

0:16:29Tyler Panznersupportedhigh

The CYP2R1 gene encodes the enzyme responsible for converting inactive supplemental vitamin D into calcifediol.

"turns out that gene, that CYP2R1 gene, and for you guys listening, a gene is instructions to make a protein. Think of a protein as a worker in the city, the city of you. The job of this protein is to take the inactive vitamin D, the form we supplement with, and turn it to the storage form that circulates in our bloodstream." (said at 0:16:29)

The CYP2R1 gene encodes cytochrome P450 family 2 subfamily R member 1, which functions as the principal hepatic microsomal vitamin D 25-hydroxylase. This enzyme converts parent vitamin D (cholecalciferol, the common supplemental and cutaneously synthesized form) into 25-hydroxyvitamin D (calcifediol / 25(OH)D), the primary circulating storage form of vitamin D in the bloodstream.

0:24:35Tyler Panznersupportedlow

Published case reports show that vitamin D toxicity requiring hospitalization occurs at blood levels of 200 to 250 ng/mL and above.

"there was a case report study that came out of someone kind of like that, but more severe. They were overdosing. Um they don't know the exact dosage, but they actually had some pretty major, you know, side effects, but they were off the chart. The highest the test could measure was 200, it was either 200 or 250 nanograms per milliliter... Had to get hospitalized for it." (said at 0:24:35)

Published case reports and endocrinology reviews corroborate that symptomatic vitamin D toxicity requiring acute medical management and hospitalization occurs with severe 25-hydroxyvitamin D elevations, with toxicity defined by concentrations above 150 ng/mL and severe clinical cases frequently exceeding standard assay upper limits (200 to 250 ng/mL).

0:11:58Tyler Panznersupportedhigh

Classical psychedelics, including psilocybin, LSD, DMT, and mescaline, produce their effects by binding to the serotonin 2A (5-HT2A) receptor.

"serotonin 2A receptor on the surface of the brain. So that's actually the receptor that classical psychedelics bind to and cause, you know, um psilocybin, LSD, DMT, mescaline." (said at 0:11:58)

Extensive pharmacological, preclinical, and human neuroimaging research establishes that classical psychedelics—such as psilocybin (via its active metabolite psilocin), LSD, DMT, and mescaline—exert their characteristic psychoactive and perceptual effects primarily through agonist or partial agonist activity at serotonin 5-HT2A receptors, particularly those located on cortical pyramidal neurons.

0:31:19Tyler Panznersupportedmoderate

Quercetin, resveratrol, and curcumin act as iron and copper chelators.

"All three of those are also iron and copper chelators." (said at 0:31:19)

Biochemical and pharmacological research confirms that quercetin, resveratrol, and curcumin possess metal-chelating properties, particularly toward redox-active transition metals such as iron (Fe) and copper (Cu). These polyphenols contain hydroxyl, catechol, or beta-diketone functional groups capable of forming coordination complexes with iron and copper ions, thereby helping suppress metal-mediated Fenton reactions and oxidative stress.

  • supports: Management of oxidative stress and other pathologies in Alzheimer's disease. (Archives of toxicology 2019) · cited 304x in the literature
    "The therapeutic potency of huperzine A and B, ginseng, curcumin and other compounds is manifested predominantly by the inhibitory action toward AChE, antioxidant or radical-scavenging and redox metal-chelating activity... Among the most promising group of substances with potential activity against AD are the flavonoids, including myricetin, morin, rutin, quercetin, fisetin, kaempferol, apigenin and glycitein, which have been shown, in vitro, to possess antiamyloidogenic and fibril-destabilization activity, as well as being able to act as metal chelators and to suppressing oxidative stress." (abstract, review text, passage verified)
    pubmedfull study (doi)
0:31:31Tyler Panznersupportedvery low

Quercetin, resveratrol, and curcumin slow down the metabolic breakdown of neurotransmitters, including adrenaline.

"They also slow down the breakdown of neurotransmitters, including adrenaline." (said at 0:31:31)

Preclinical in vitro and animal studies demonstrate that quercetin, resveratrol, and curcumin can inhibit monoamine oxidase (MAO-A and MAO-B) and/or catechol-O-methyltransferase (COMT). These enzymes are the primary pathways responsible for the metabolic breakdown of monoamines and catecholamine neurotransmitters, including adrenaline (epinephrine), noradrenaline (norepinephrine), dopamine, and serotonin. However, because evidence is derived from enzyme assays and rodent models, in vivo translation in humans at standard dietary doses remains limited by bioavailability.

0:38:40Tyler Panznersupportedmoderate

Histamine, sulfites, glutamate, and adrenaline are excitatory to the brain and excite brain cells.

"Sulfur, or more specifically sulfites, glutamate, and adrenaline. Those are four that are all excitatory to the brain. They pump the gas. They rev up the brain and excite our brain cells." (said at 0:38:40)

Published neurobiological literature establishes that glutamate is the primary excitatory neurotransmitter in the mammalian central nervous system, and that histamine and adrenergic signaling (adrenaline/epinephrine and noradrenaline) act as central excitatory and arousal-promoting neuromodulators. Histamine directly increases neuronal excitability and depolarisation predominantly via H1 and H2 receptors, and positively modulates N-methyl-D-aspartate (NMDA) glutamate receptors, while adrenergic signaling similarly drives arousal and autonomic excitation.

0:39:00Tyler Panznersupportedlow

Excess levels of histamine, sulfites, glutamate, and adrenaline are linked to anxiety.

"All four of those in excess levels are linked to anxiety." (said at 0:39:00)

Preclinical and clinical evidence links elevated levels or dysregulation of histamine, sulfites, glutamate, and adrenaline (noradrenergic signaling) to anxiety and anxiety-like behaviors. Preclinical rodent studies demonstrate that excessive sulfite intake induces anxiety-like behaviors, and elevated central histaminergic transmission potentiates stress-induced anxiety. In human psychiatric research, glutamatergic excitotoxicity and dysregulation of noradrenergic/adrenergic sympathetic stress pathways are recognized central mechanisms in anxiety disorders. The certainty is low due to primary reliance on animal models for sulfite-induced anxiety.

0:39:04Tyler Panznersupportedmoderate

Histamine, glutamate, and sulfur dysregulation are linked to OCD, depression, ADHD, Tourette's syndrome, and autism spectrum disorder.

"if you look at histamine, glutamate, sulfur, it's also linked to OCD, depression, ADHD, Tourette's syndrome, autism spectrum disorder, so many different things." (said at 0:39:04)

Scientific literature extensively links dysregulation of neurotransmitter and metabolic pathways—specifically glutamate, histamine, and sulfur-related pathways (such as sulfur amino acid/transsulfuration metabolism and hydrogen sulfide signaling)—to neuropsychiatric and neurodevelopmental conditions including obsessive-compulsive disorder (OCD), depression, attention-deficit/hyperactivity disorder (ADHD), Tourette's syndrome, and autism spectrum disorder (ASD). Systematic reviews and neurobiological literature confirm alterations in central glutamatergic signaling and metabolite levels across pediatric and adult ADHD, ASD, OCD, and major depressive disorder (e.g., measured via magnetic resonance spectroscopy). Furthermore, genetic and neurochemical studies demonstrate the role of the histaminergic system (e.g., histidine decarboxylase mutations and receptor dysregulation) in the pathogenesis of Tourette's syndrome and OCD.

0:40:20Tyler Panznersupportedhigh

Exercise causes the release of histamine, which functions to dilate blood vessels for increased blood flow.

"Exercise releases histamine. And that's not necessarily a bad thing, but that's how we dilate our blood vessels to get more blood flow." (said at 0:40:20)

Human physiological studies and clinical trials show that exercise induces the release of histamine within skeletal muscle, which acts on histamine H1 and H2 receptors to produce sustained post-exercise vasodilation (hyperemia) and enhanced blood flow. Combined pharmacological blockade of H1 and H2 receptors suppresses post-exercise leg blood flow and vasodilation in both sedentary and endurance-trained individuals.

0:43:25Tyler Panznersupportedhigh

Supplemental glutamine can be converted in the body into both glutamate and ammonia.

"Glutamate: glutamine is the biggest mistake I see people make. It's recommended so often for the gut. Hey, does it help those enterocytes link together? Yes, it does. But that also can get converted into not just glutamate, but also ammonia as well, which can cause issues for people." (said at 0:43:25)

Glutamine catabolism in human physiology is mediated primarily by the enzyme glutaminase (such as GLS1 and GLS2), which hydrolyzes glutamine into glutamate and ammonia (ammonium ion). In reverse, glutamine synthetase ligates ammonia and glutamate to form glutamine. When supplemental or dietary glutamine is metabolized by enterocytes, the liver, kidneys, or the brain, glutaminase-mediated conversion into both glutamate and ammonia is a standard and well-characterized biochemical pathway.

0:44:25Tyna Moore (host)supportedhigh

Vitamin B6 is a required cofactor for converting glutamate into the inhibitory neurotransmitter GABA.

"if you don't have enough B6 and, like you said, the pathways and just the co-factors are not there, then it goes glutamate, which is an excitatory neurotoxin, versus GABA, which is your major inhibitory neurotransmitter, which is calming." (said at 0:44:25)

Vitamin B6 in its active coenzyme form, pyridoxal 5'-phosphate (PLP), is an essential cofactor for glutamic acid decarboxylase (GAD), the primary enzyme that converts the excitatory neurotransmitter glutamate into the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Deficiency or inhibition of PLP synthesis impairs GAD activity and reduces GABAergic neurotransmission.

0:52:05Tyler Panznersupportedmoderate

Rising estrogen levels, such as during the days leading up to ovulation, cause histamine levels to increase.

"Now, what else can raise histamine? Estrogen can. So, work with a lot of women, and around ovulation, sure you know this, estrogen goes up, histamine follows up with it as well." (said at 0:52:05)

Preclinical and clinical evidence indicates that estrogen promotes mast cell activation and histamine release, and that allergic and mast-cell-mediated responses peak during the mid-cycle/ovulatory phase when estrogen levels are highest. In vitro and animal studies demonstrate that estradiol directly induces mast cell migration, maturation, and degranulation, leading to histamine release. In human studies of cycling women, mast cell reactivity and allergen skin-test responses show significant peaks at mid-cycle corresponding to peak estrogen concentrations.

0:59:50Tyler Panznersupportedlow

A study found that individuals with chronic pain scored significantly higher in perfectionism and lower in self-compassion compared to control groups.

"Now this study came out that was linking perfectionism to chronic pain. So they scored people based on perfectionism for themselves, holding others to impossibly high standards. So they were very high in that, the chronic pain versus the control group. And then they had low self-compassion." (said at 0:59:50)

A 2025 publication evaluated perfectionism, self-compassion, and self-efficacy across two survey cohorts comparing adults with chronic pain to pain-free controls (Study 1: n = 237 with chronic pain vs. n = 237 controls; Study 2: n = 294 with chronic pain vs. n = 278 controls). Across both cohorts, individuals experiencing chronic pain scored significantly higher on measures of perfectionism (specifically socially prescribed perfectionism in Study 1, and overall perfectionism in Study 2) and significantly lower in self-compassion compared to control groups without pain. Because the evidence relies on cross-sectional self-report surveys, the certainty of evidence is low.

1:00:35Tyler Panznersupportedmoderate

Genetic variants in glutamate signaling pathways are linked to chronic pain.

"So we know genetic variants in glutamate signaling are linked to chronic pain." (said at 1:00:35)

Large-scale genome-wide association studies (GWAS) and functional genomic analyses have demonstrated that genetic variants associated with chronic pain risk are significantly enriched in glutamatergic pathways and excitatory glutamatergic neurons. In a meta-analysis of over 1.2 million individuals integrated with human dorsal root ganglia and brain single-cell transcriptomics, pain-associated genetic loci and heritability were strongly enriched in central glutamatergic neurons and peripheral sensory neurons with pathways implicated in glutamatergic signaling. Additionally, specific polymorphisms in genes regulating glutamatergic receptor trafficking (such as CACNG2/stargazin, which regulates AMPA receptor trafficking) have been linked to human chronic pain susceptibility.

0:43:41Tyler Panznersupportedmoderate

Glutamine supports intestinal epithelial integrity by helping enterocytes link together.

"Glutamate: glutamine is the biggest mistake I see people make. It's recommended so often for the gut. Hey, does it help those enterocytes link together? Yes, it does." (said at 0:43:41)

Published experimental studies and reviews consistently show that glutamine plays a critical role in intestinal barrier function by promoting the expression, assembly, and localization of tight junction proteins (such as claudins, occludin, and zonula occludens proteins) that connect adjacent enterocytes, thereby reducing paracellular permeability.

0:59:30Tyler Panznersupportedlow

Histamine and glutamate signaling pathways are directly involved in the cell signaling of chronic pain.

"But first, we know that histamine and glutamate signaling and therefore sulfur signaling, these are linked to chronic pain. It's literally the cell signaling of pain." (said at 0:59:30)

Preclinical research demonstrates that both glutamate and histamine signaling pathways directly mediate nociception and neuroinflammation in chronic neuropathic and inflammatory pain. Glutamate serves as the primary excitatory neurotransmitter in primary afferent nociceptors and central spinal pain pathways, driving hyperalgesia via receptors such as NMDA subunit GluN2B. Histamine acts via H1-H4 receptors on sensory neurons and glial cells to modulate pain hypersensitivity and neuroimmune responses.

1:02:20Tyna Moore (host)supportedmoderate

Exercise, diet, sunlight exposure, circadian rhythms, sleep, and stress levels impact gene expression and the epigenetic profile.

"we know that exercise, the diet that we eat, the sun that we get, the circadian rhythm, the sleep, the stress levels, those all impact the genes and how those genes express themselves and the epigenetic profile." (said at 1:02:20)

Extensive research in environmental and lifestyle epigenetics demonstrates that factors such as physical exercise, diet, sleep, circadian alignment, psychological stress, and environmental exposures (including sunlight/UV) modulate gene expression through epigenetic mechanisms. These mechanisms primarily include DNA methylation, histone modifications, and non-coding RNA expression.

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.