HoldsUp

Charles Brenner

Charles Brenner is a researcher working in the fields of biochemistry and cellular metabolism. His research focuses on NAD+ homeostasis, metabolic regulation, and the physiological effects of nicotinamide riboside supplementation in conditions such as mild cognitive impairment, long-COVID, and cancer survivorship. He also investigates metabolic signaling nodes in cancer, liver disease, and genetic metabolic disorders.

56 claims checked on air: 2 context 2 contradicted 4 overstated 42 supported 6 unverified

What they said on air - citing their own research

22 citing their own research

0:03:55supportedmoderatetheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

Patients with mitochondrial disease, such as adult-onset mitochondrial myopathy, have abnormally low blood NAD levels.

"like we discovered in collaboration with University of Helsinki a number of years ago that people with mitochondrial disease that were thought to primarily have muscle mitochondrial myopathy are walking around with low blood NAD." (said at 0:03:55)

A 2020 clinical study conducted in collaboration with the University of Helsinki (Pirinen et al., Cell Metabolism) demonstrated systemic NAD+ deficiency, specifically characterized by depleted blood and muscle NAD+ levels, in patients with adult-onset mitochondrial myopathy compared to matched controls.

0:08:04supportedlowtheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

Coronavirus infection transcriptionally activates five distinct members of the PARP superfamily in infected tissues.

"we published a paper in 2020 on the effect of coronavirus infection not just on mouse liver, but on human lung samples that we were able to get from morgues and from like databases where they had COVID infection. And just to come back to the PARP question, we found five different members of the PARP superfamily that were transcriptionally activated by coronavirus infection." (said at 0:08:04)

A 2020 study by Brenner and colleagues (Heer et al., PMID 33051211) evaluated the transcriptomic response to coronavirus infection across cell lines, mouse models, and human post-mortem COVID-19 lung tissue datasets. The authors found that infection by murine hepatitis virus (MHV) and SARS-CoV-2 transcriptionally upregulates noncanonical, mono(ADP-ribosylating) members of the PARP superfamily (including PARP7, PARP9, PARP10, PARP12, and PARP14), which consume cellular NAD+ during the host innate immune response.

0:10:27supportedhightheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

Supplementing with 300 milligrams or more of NAD precursor vitamins produces a substantive increase in the circulating blood NAD metabolome.

"Well, when people take substantive amounts of NAD precursor vitamins into the 300 milligram-plus, you can see a substantive change in people's circulating NAD metabolome." (said at 0:10:27)

Human clinical trials and pharmacokinetic studies demonstrate that oral supplementation with NAD precursor vitamins—such as nicotinamide riboside (NR)—at doses of 300 mg or greater produces a substantive, dose-dependent increase in the circulating blood NAD+ metabolome. In a pharmacokinetic trial, single oral doses of 100, 300, and 1,000 mg of NR resulted in dose-dependent increases in the blood NAD+ metabolome (Trammell et al., 2016). Furthermore, an 8-week randomized, double-blind, placebo-controlled trial found that daily supplementation with 300 mg and 1,000 mg of NR significantly increased whole blood NAD+ concentrations by 51% and 142%, respectively, within 2 weeks, maintaining this elevation throughout the study (Conze et al., 2019).

0:13:16supportedmoderatetheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

Heart failure, central and peripheral neurodegeneration, and UV sun exposure deplete or disturb NAD system levels in affected tissues.

"But for sure in a lot of diseasing conditions the NAD system really comes under attack. So in heart failure the NAD system comes under attack; in central and peripheral neurodegeneration, comes under attack; sun exposure, it comes under attack." (said at 0:13:16)

Published molecular and preclinical literature confirms that the NAD+ metabolome is depleted or compromised across these conditions. In human and rodent failing hearts, myocardial NAD+ levels decrease significantly (accompanied by downregulation of the salvage enzyme NAMPT and upregulation of NMRK2). In central and peripheral neurodegenerative conditions (such as amyotrophic lateral sclerosis and peripheral neuropathies), axonal injury and programmed axon degeneration trigger rapid NAD+ depletion mediated by activation of the NADase SARM1 or deficits in NAD biosynthetic enzymes (NAMPT, NMNAT1/2). In skin subjected to ultraviolet (UV) radiation, photic DNA damage triggers hyperactivation of NAD-consuming poly(ADP-ribose) polymerases (such as PARP1) and dysregulates NAD+-dependent sirtuin signaling, disrupting cellular NAD homeostasis.

0:14:01supportedvery lowtheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

High-fat diet-induced type 2 diabetes in mice disturbs the liver NAD system and degrades NADPH levels required for detoxifying reactive oxygen species.

"So from 2016, one of our first mouse experiments was overfeeding mice. We gave them a high-fat diet. We pushed them all the way into type 2 diabetes. Their liver NAD system was disturbed and NADPH was the center of that. So their ability to detoxify reactive oxygen species was degraded by being fat and being insulin resistant." (said at 0:14:01)

A 2016 study in male C57BL/6J mice fed a high-fat diet to induce prediabetes and type 2 diabetes found that hepatic NADP+ and NADPH levels were significantly degraded compared to controls. NADPH is essential for maintaining antioxidant defense systems (such as the glutathione system) to detoxify reactive oxygen species. Because the evidence is derived from animal experiments and biochemical mechanisms, the GRADE certainty is very low.

0:16:07supportedhightheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

NAD synthesis and NAD-dependent metabolic processes are regulated by circadian time-of-day cues, and age-related loss of chronosynchrony in mice disrupts the NAD system.

"for sure in mice we've looked at young mice that have really good chronosynchrony and older mice that are kind of losing their synchrony, and the NAD system becomes disturbed. There's a lot of time-of-day cues that go into NAD synthesis and NAD-dependent metabolic processes." (said at 0:16:07)

The speaker's claim is supported by controlled laboratory studies in mice. Circadian time-of-day cues regulate NAD synthesis and NAD-dependent metabolic processes (such as SIRT1 activity and mitochondrial respiration rhythms) via feedback loops involving the rate-limiting enzyme nicotinamide phosphoribosyltransferase (NAMPT). Studies comparing young mice with good chronosynchrony to older mice demonstrate that aging impairs circadian control and disrupts NAD-related metabolic processes and metabolite oscillations in tissues like the liver and brain, while restoring NAD levels can rescue these circadian metabolic dynamics.

0:18:54supportedmoderatetheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

In a randomized controlled crossover trial of older men, nicotinamide riboside significantly reduced inflammatory markers including IL-6 and IL-10 despite failing to improve grip strength.

"Nobody's grip strength got better, and then they went to the secondary outcomes and they found NR was strongly anti-inflammatory, like greatly lowering IL-6, IL-10, and other markers of inflammation." (said at 0:18:54)

The claim accurately reflects findings from a randomized, double-blind, placebo-controlled crossover trial by Elhassan et al. (2019) in 12 aged men (70–80 years old) receiving 1 g/day of nicotinamide riboside (NR) for 21 days. The trial found that NR supplementation did not alter skeletal muscle mitochondrial bioenergetics or functional measures (such as grip strength/muscle function), but secondary analyses demonstrated a significant depression in circulating inflammatory cytokines (including IL-6, IL-5, IL-2, and IL-10, along with down-regulated muscle transcriptomic inflammatory pathways).

0:20:04needs contextmoderatetheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

In a crossover trial evaluating nicotinamide riboside in older men, the anti-inflammatory effect exhibited a carryover that persisted for three weeks into the subsequent placebo period.

"In fact, it was so strong that the people that had the NR first followed by placebo still had lower anti-inflammatory results after three weeks on placebo." (said at 0:20:04)

In a randomized, double-blind, crossover study of 12 older men receiving 1 g/day of nicotinamide riboside (NR) or placebo for 21 days (PMID 31412242), NR supplementation depressed circulating levels of inflammatory cytokines (such as IL-6, IL-5, IL-2, and TNF-alpha). An observed carryover effect occurred in the group receiving NR first followed by placebo, with inflammatory cytokines remaining suppressed during the subsequent period. The speaker's phrasing ('lower anti-inflammatory results') is slightly confused in terminology (meaning lower pro-inflammatory cytokines / reduced inflammation), but accurately reflects the findings of a persistent anti-inflammatory carryover effect in this small trial.

0:25:35overstatedmoderatetheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

Oral nicotinamide riboside supplementation improves cerebral blood flow in patients with mild cognitive impairment.

"There are small clinical studies that show that oral nicotinamide riboside improves cerebral blood flow in people with mild cognitive impairment." (said at 0:25:35)

Small randomized controlled trials of oral nicotinamide riboside (NR) in older adults with mild cognitive impairment (MCI) have not demonstrated an overall improvement in cerebral blood flow (CBF). In a 12-week pilot trial of 42 participants, NR produced no significant improvement in total CBF compared to placebo, although exploratory analyses noted potential increases in regional CBF in the hippocampus. Another 10-week pilot RCT in 20 MCI patients found that NR did not increase CBF and was associated with a reduction in CBF within the default mode network before correction for multiple comparisons.

0:25:52supportedmoderatetheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

A clinical study in long COVID patients demonstrated within-group improvements in executive function following nicotinamide riboside supplementation.

"So there is a long COVID study um in which um all of the people that are enrolled have long COVID, so they have complaints about their executive function, depression, their sleep quality, um their mood. And um there was a recent study, I think in the last month or two, it's Wu et al. and I think it's Lancet eClinicalMedicine or something like that. I'm a co-author on the paper um that shows that there's within-group improvements." (said at 0:25:52)

A double-blind, randomized controlled trial by Wu et al. (2025) published in eClinicalMedicine evaluated nicotinamide riboside (NR; 2000 mg/day) in 58 participants with long COVID. While the trial found no statistically significant between-group differences compared with placebo on primary cognitive outcomes (including the Trail Making Test-B measuring executive functioning) or secondary symptom scores, post-hoc exploratory analyses combining participants during their first 10 weeks of NR supplementation demonstrated significant within-group improvements from baseline in executive functioning, fatigue severity, sleep quality, and depressive symptoms.

0:31:48supportedmoderatetheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

Exercise increases the gene expression of NAD biosynthetic enzymes in humans.

"And we do have some clinical evidence showing that exercise leads to an increase in the gene expression of NAD biosynthetic enzymes. So I recently published that with a group in Germany" (said at 0:31:48)

Clinical trial evidence in humans demonstrates that exercise increases the gene expression and protein abundance of key NAD+ biosynthetic enzymes, notably nicotinamide phosphoribosyltransferase (NAMPT, the rate-limiting enzyme of the NAD+ salvage pathway). In human randomized crossover and longitudinal trials, both acute exercise (such as high-intensity interval training and moderate-intensity continuous training) and endurance exercise training significantly upregulated NAMPT and other NAD+ biosynthetic enzymes in human peripheral blood mononuclear cells and skeletal muscle.

0:38:17supportedvery lowtheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

Maternal nicotinamide riboside supplementation results in mouse offspring with higher lean mass at weaning that is maintained throughout their lives.

"And what we found is that the offspring of supplemented mothers had better lean mass um at the time of weaning that they were able to maintain for their whole lives." (said at 0:38:17)

A 2019 preclinical study in mice (Ear et al., Cell Reports) led by Charles Brenner investigated maternal nicotinamide riboside (NR) supplementation during lactation. The study found that pups of NR-supplemented mothers had increased size and developmental advantages at weaning that persisted into adulthood, conferring lasting benefits in physical performance, glycemic control, and neurogenesis. Because the evidence is derived entirely from animal (mouse) models, the certainty of evidence for human outcomes is graded as very low.

0:38:27supportedvery lowtheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

Maternal nicotinamide riboside supplementation improves physical motor development and balance beam performance in mouse offspring.

"They had um faster uh mechanical, physical development, so their performance on like a balance beam type thing was better if the mom was supplemented." (said at 0:38:27)

A 2019 mouse study by Ear et al. found that maternal supplementation with nicotinamide riboside (NR) during lactation enhanced offspring development, including faster juvenile neurodevelopmental/physical milestones and superior motor and physical performance (such as motor coordination and balance tests) in adult offspring. Because these findings are derived entirely from preclinical rodent experiments, the certainty of the evidence for broader human application is very low.

0:38:39supportedvery lowtheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

Maternal nicotinamide riboside supplementation reduces anxiety-like behavior, improves Morris water maze performance, and increases adult hippocampal neurogenesis in mouse offspring.

"Um they had lower fear and anxiety to the degree to which you can test such things in in mice. Um so they did better on a Morris water maze, and they even had better adult hippocampal neurogenesis if the mom had been supplemented." (said at 0:38:39)

A 2019 mouse study by Ear et al. (Cell Reports) investigated the effects of maternal nicotinamide riboside (NR) supplementation during lactation on offspring development. The study found that adult mouse offspring of supplemented mothers showed significant neurobehavioral advantages, including reduced anxiety-related behaviors (anti-anxiety phenotype), improved spatial memory (measured by the Morris water maze), and enhanced adult hippocampal neurogenesis. Because these findings are derived entirely from preclinical animal models, certainty of evidence is very low.

0:40:19supportedvery lowtheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

Nicotinamide riboside-supplemented mother mice produce more milk during lactation than non-supplemented mother mice.

"The NR-supplemented moms produced more milk than the non-supplemented moms." (said at 0:40:19)

A 2019 preclinical study in mice (Ear et al., Cell Reports) demonstrated that maternal supplementation with nicotinamide riboside (NR) during the postpartum period increased lactation, mammary biosynthetic programs, and prolactin synthesis compared to non-supplemented controls. Because this evidence is derived entirely from animal models, the certainty is graded as very low for translation to human biology, but it directly supports the specific claim about mother mice.

0:41:27supportedvery lowtheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

During lactation in mothers, the liver NAD system declines while NAD precursors accumulate in the mammary gland to support lactation.

"And actually the liver NAD system declines in a non-supplemented mother. The blood NAD metabolism increases, and it basically accumulates in the mammary in order to support the mammary biosynthetic program." (said at 0:41:27)

Preclinical research in mouse models demonstrates that during postpartum lactation, the maternal liver NAD metabolome becomes depressed while circulation of NAD metabolites in the blood increases, driving a greater than 20-fold accumulation of NAD+ and NADP+ in the mammary gland to support milk production and mammary biosynthetic programs. Because this mechanism has currently been demonstrated primarily in preclinical animal models, the certainty for human mothers is very low.

0:54:02supportedvery lowtheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

Nicotinamide cannot boost NAD in heart failure animal models because the failing heart overexpresses NMRK2 and relies on the nucleoside pathway.

"Like in the heart failure experiments, nicotinamide can't actually boost the NAD in the failing heart because in the failing heart, it's overexpressing a gene called NMRK2, nicotinamide riboside kinase 2." (said at 0:54:02)

Preclinical studies in mouse models of heart failure (dilated cardiomyopathy and transverse aorta constriction) and human failing heart biopsies show that the failing heart downregulates nicotinamide phosphoribosyltransferase (the enzyme that recycles nicotinamide into NAD+) and dramatically upregulates nicotinamide riboside kinase 2 (NMRK2, up to 40-fold). As a result, the failing heart shifts metabolic reliance to nicotinamide riboside for NAD+ synthesis over nicotinamide. GRADE certainty is very low because the findings are based on animal models and in vitro cardiomyocyte experiments.

1:10:42overstatedmoderatetheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

Eight randomized clinical trials have shown beneficial effects of NR in lowering inflammation.

"eight randomized clinical trials showing beneficial effects of NR in lowering inflammation could be broadly useful for for human aging." (said at 1:10:42)

While individual small randomized controlled trials (RCTs) have reported reductions in specific inflammatory markers following nicotinamide riboside (NR) supplementation—such as decreased circulating inflammatory cytokines in 12 aged men and reduced sputum interleukin-8 in adults with COPD—claiming that eight RCTs have established beneficial anti-inflammatory effects overstates the clinical trial landscape. Systematic synthesis of human NAD+ precursor trials shows that clinical, metabolic, and systemic outcomes in humans remain mixed, highly endpoint-specific, and frequently null.

1:11:52overstatedlowtheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

Nicotinamide riboside has been shown to improve cerebral blood flow in patients with mild cognitive impairment.

"I'm on at least one paper on mild cognitive impairment where nicotinamide riboside is beginning to show some, you know, important signs like improving cerebral blood flow, you know, in this population." (said at 1:11:52)

Randomized controlled pilot trials evaluating nicotinamide riboside (NR) in adults with mild cognitive impairment (MCI) have not demonstrated significant overall improvements in cerebral blood flow (CBF). In a 12-week randomized controlled pilot trial (n=42), NR supplementation significantly raised blood NAD+ levels but showed no improvement in total CBF or cognitive function compared to placebo; exploratory post hoc analyses merely suggested potential regional increases in hippocampal CBF. Another small pilot trial (n=20) found no enhancement of CBF following 10 weeks of NR supplementation. Characterizing NR as having established improvements in cerebral blood flow overstates preliminary, exploratory findings from small pilot studies.

1:13:30supportedhightheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

The 2018 Dollerup et al. trial of NR in older Danish men failed its primary endpoints of weight loss and insulin sensitivity, but showed a reduction in liver fat from ~21% to 11% (p = 0.13).

"There was a trial was done, I think it was Dollerup et al., 2018, and I'm a co-author on on the first paper, in which the hypothesis to be tested was that NR was going to improve weight loss and insulin insulin sensitivity in 13 weeks as a monotherapy in 70-year-old Danish men... in terms of the topline results, it failed. But then we went in and we looked at everything else, right? And so we found that um it was about an N of 20 I think in placebo and NR, and there was quite a big effect on hepatic fat. Like a difference of um something like 21% down to 11% fat fat in the liver, like 10 absolute percent points... when you calculate a p-value, it was p = .13" (said at 1:13:30)

The 2018 randomized, double-blind, placebo-controlled trial by Dollerup et al. evaluated 12 weeks of dietary nicotinamide riboside (NR; 1000 mg twice daily vs. placebo) in 40 obese, insulin-resistant men aged 40–70 years (NCT02303483). The study found no statistically significant improvements in primary metabolic endpoints, including insulin sensitivity (measured by hyperinsulinemic-euglycemic clamp), endogenous glucose production, lipid oxidation, or body composition. Secondary magnetic resonance spectroscopy of intrahepatic lipid content did not reach statistical significance (p = 0.13).

1:16:55supportedmoderatetheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

The 2019 clinical trial by Elhassan et al. showed that NR supplementation significantly lowered inflammation.

"It wasn't until around 2019 that Elhassan et al. in another, you know, topline failure trial showed, wow, the inflammation is is much lower." (said at 1:16:55)

The 2019 randomized, double-blind, placebo-controlled crossover trial by Elhassan et al. (n = 12 aged men receiving 1 g/day of nicotinamide riboside for 21 days) found that while NR did not alter skeletal muscle mitochondrial bioenergetics (a primary metabolic endpoint), it significantly depressed levels of circulating inflammatory cytokines and induced anti-inflammatory transcriptomic signatures in muscle.

1:29:55supportedhightheir own paperHow To Boost NAD Levels To Fight Inflammation, Improve Recov

Niagen has undergone the FDA process to be recognized as Generally Recognized as Safe (GRAS) and accepted as a New Dietary Ingredient (NDI).

"Niagen went through the process of being a uh compound that is generally regarded as safe and as a new dietary ingredient" (said at 1:29:55)

The statement accurately reflects the regulatory history of NIAGEN (nicotinamide riboside chloride). Published clinical trials documenting the safety of NIAGEN confirm that it has attained Generally Recognized as Safe (GRAS) status for use in food products and has been the subject of New Dietary Ingredient (NDI) notifications submitted to the FDA for use in dietary supplements.

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