Stress

Nrf2 activators and transcriptomic clocks

gettingwell4 2-3 stars Required further work, Epigenetics, Stress , , , , ,

Two preprint studies looked at making transcriptional aging clocks using Nrf2 activators. Let’s start with a 2025 nematode study that used constant exposure to sulforaphane at different concentrations:

“To explore the potential of sulforaphane as a candidate natural compound for promoting longevity more generally, we tested the dose and age-specific effects of sulforaphane on C. elegans longevity, finding that it can extend lifespan by more than 50% at the most efficacious doses, but that treatment must be initiated early in life to be effective. We then created a novel, gene-specific, transcriptional aging clock, which demonstrated that sulforaphane-treated individuals exhibited a “transcriptional age” that was approximately four days younger than age-matched controls, representing a nearly 20% reduction in biological age.

The clearest transcriptional responses were detoxification pathways, which, together with the shape of the dose-response curve, indicates a likely hormetic response to sulforaphane. The hormetic, stress-pathway inducing properties of sulforaphane may indicate that many beneficial dietary supplements work in a fairly generic fashion as mild toxins rather than being driven by the biochemical properties of the compounds themselves (e.g., as antioxidants).

These results support the idea that robust longevity-extending interventions can act via global effects across the organism, as revealed by systems level changes in gene expression.”

https://www.biorxiv.org/content/10.1101/2025.05.11.653363v1 “The broccoli derivative sulforaphane extends lifespan by slowing the transcriptional aging clock”

There are difficulties in researchers translating nematode studies to mammals and humans. Nematodes lack a homolog to the Keap1 protein, which is sulforaphane’s main mammalian target to activate Nrf2.

A 2024 study developed various mammalian epigenetic clocks:

“A unified transcriptomic model of mortality that encompasses both aging and various models of lifespan-shortening and longevity interventions (i.e., mortality clocks) has been lacking. We conducted an RNA-seq analysis of mice subjected to 20 compound treatments in the Interventions Testing Program (ITP).

We sequenced the transcriptomes of a large cohort of ITP mice subjected to various neutral and longevity interventions, expanded the dataset with publicly available gene expression data representing organs of mice and rats across various strains and lifespan-regulating interventions, connected these models with survival data, and performed a meta-analysis of aggregated 4,539 rodent samples, which allowed us to identify multi-tissue transcriptomic signatures of aging, mortality rate, and maximum lifespan.

Aging and mortality were characterized by upregulation of genes involved in inflammation, complement cascade, apoptosis, and p53 pathway, while oxidative phosphorylation, fatty acid metabolism, and mitochondrial translation were negatively associated with mortality, both before and after adjustment for age.

Utilizing the aggregated dataset, we developed rodent multi-tissue transcriptomic clocks of chronological age, lifespan-adjusted age, and mortality. While the chronological clock could distinguish the effect of detrimental genetic and dietary models, it did not show a decrease in biological age in response to longevity interventions. In contrast, clocks of lifespan-adjusted age and mortality both captured aging-associated dynamics and correctly predicted the effect of lifespan-shortening and extending interventions.

Transcriptomic biomarkers developed in this study provide an opportunity to identify interventions promoting or counteracting molecular mechanisms of mortality, and characterize specific targets associated with their effects at the level of cell types, intracellular functional components, and individual genes. Our study underscores the complexity of aging and mortality mechanisms, the interplay between various processes involved, and the clear potential for developing therapies to extend healthspan and lifespan.”

https://www.biorxiv.org/content/10.1101/2024.07.04.601982v1.full “Transcriptomic Hallmarks of Mortality Reveal Universal and Specific Mechanisms of Aging, Chronic Disease, and Rejuvenation”

This second study’s references included an ITP study curated in Astaxanthin and aging, which stated:

“Despite the fact that the average diet contained 1840 ppm astaxanthin (only 46% of the target), median lifespans of male UM-HET3 mice were significantly improved. Amounts of dimethyl fumarate (DMF) in the diet averaged 35% of the target dose, which may explain the absence of lifespan effects.”

So screw-ups in making both astaxanthin and DMF mouse chows ended up with study data that didn’t measure the full lifespan impacts of activating transcription factor Nrf2. I’ll assert that such faulty data may have deviated this second study by downplaying Nrf2 activation’s impact on aging, chronic disease, and rejuvenation.

Sponsors may be less likely to be presented sulforaphane and other Nrf2 activator candidates for future aging and chronic disease studies as this first study suggests, thinking that these have already been studied in mammals. Well, maybe these compounds haven’t been accurately studied. There’s no effective way to fix a rodent study’s missing DMF Nrf2 data and faulty astaxanthin Nrf2 data to train an epigenetic clock in this second study.

I could be wrong about this second study using faulty astaxanthin Nrf2 data. It was cited as Reference 27 in the Introduction as an ITP study, but not specifically cited in the Method section. I don’t know how findings such as one of Nrf2’s target genes (“Remarkably, one of the top genes positively associated with maximum lifespan and negatively associated with chronological age and expected mortality was Gpx1, encoding the selenoprotein glutathione peroxidase 1″) and a Nrf2 specific pathway (Phase II) (“Pathways positively associated with lifespan and negatively with mortality, both before and after adjustment for age, included..xenobiotic metabolism..”) were made without Reference 27. Neither of the above studies has been peer reviewed yet.

Practice what you preach, or shut up

gettingwell4 0-1 star Wasted resources, Acetylcholine, Amygdala, Anterior cingulate cortex, Beliefs, Brain development, Brain hemispheres, Brainstem, Cerebellum, Cerebrum, Cortisol, Dopamine, Epigenetics, Glutamate, Hippocampus, Hypothalamus, Immune system, Limbic system, Locus coeruleus, Lower brain, Memory, Neurochemicals, Serotonin, Stress, Thalamus , , , , , ,

A 2025 review subject was sulforaphane and brain health. This paper was the latest in a sequence where the retired lead author self-aggrandized his career by citing previous research.

He apparently doesn’t personally do what these research findings suggest people do. The lead author is a few weeks older than I am, and has completely white hair per an interview (Week 34 comments). I’ve had dark hair growing in (last week a barber said my dark hair was 90%) since Week 8 of eating broccoli sprouts every day, which is a side effect of ameliorating system-wide inflammation and oxidative stress.

If the lead author followed up with what his research investigated, he’d have dark hair, too. Unpigmented white hair and colored hair are both results of epigenetics.

Contrast this lack of personal follow-through of research findings with Dr. Goodenowe’s protocol where he compared extremely detailed personal brain measurements at 17 months and again at 31 months. He believes enough in his research findings to personally act on them, and demonstrate to others how personal agency can enhance a person’s life.

It’s every human’s choice whether or not we take responsibility for our own one precious life. I’ve read and curated on this blog many of this paper’s references. Five years ago for example:

So do more with their information than just read.

https://www.mdpi.com/2072-6643/17/8/1353 “Sulforaphane and Brain Health: From Pathways of Action to Effects on Specific Disorders”

Year Five of Changing to a youthful phenotype with sprouts

gettingwell4 4-5 stars Advanced knowledge, Epigenetics, Immune system, Memory, Stress

1. I’ve continued daily practices from Year Four to experience another year without being sick! I’ll get a set of Labcorp tests in a week to see if anything is sneaking up on me.

Really think that Brassica clinical trials should last years, not weeks. Once people get over the fact that broccoli, red cabbage, and mustard sprouts will never taste good because their compounds are plants’ defenses against predators, they’ll overlook that in favor of health benefits. Avena sativa oat sprouts don’t have a palatability problem.

2. Daily supplements have changed a little:

  • Started taking a quercetin supplement suggested in a comment to Year One as helpful for seasonal allergies (it doesn’t do that for me). Repeatedly rinsing and soaking the salt out of capers for quercetin content became too much of a nuisance, and the results didn’t always taste right;
  • Stopped taking Prodrome supplements because of unsustainable high costs;
  • Started taking Ovega 3 algae oil DHA 420 mg/EPA 140 mg twice a day in their place;
  • Substituted flax oil 1400 mg once a day for Balance oil;
  • Started taking 2 g magnesium L-threonate;
  • Upped taurine intake from 5 to 6 grams;
  • Upped D3 by 25 mcg to a daily 4400 IU;
  • Reduced chondroitin sulfate by 1.8 g since my joints are doing fine;
  • Stopped soy lecithin in favor of eating three raw eggs.

3. I injured my left shoulder in May 2024 by overdoing upper body exercises, and stopped seven months to recover. Gained thirty pounds during that layoff, and have worked off ten pounds with new routines since then.

I’m no longer dogmatic about aerobic exercise / beach walks. I’ll go over to the beach before sunrise when it isn’t raining or windy, or wait until the afternoon for weather to improve, rather than walk 30 minutes a day irregardless.

2025 α-ketoglutarate research

gettingwell4 4-5 stars Advanced knowledge, Dopamine, Epigenetics, Glutamate, Hippocampus, Immune system, Limbic system, Memory, Neurochemicals, Serotonin, Stress , , , ,

I haven’t mentioned α-ketoglutarate for a while, although I’ve taken it twice a day for several years. Here are four 2025 papers on α-ketoglutarate, starting with a review of its role in bone health:

“α-Ketoglutarate (α-KG) serves as a pivotal intermediate in various metabolic pathways in mammals, significantly contributing to cellular energy metabolism, amino acid metabolism, and other physiological processes. α-KG may be a therapeutic target for a variety of bone-related diseases, such as osteoporosis, osteoarthritis, and rheumatoid arthritis, because of its role in maintaining metabolic balance of bone.

α-KG, as a rate-determining mitochondrial intermediate, is crucial in cell energy metabolism because it connects intracellular carbon and nitrogen metabolism between isocitrate and succinyl coenzyme A. Additionally, α-KG is closely involved in the amino acid cycle. As a precursor of amino acids such as glutamine and glutamic acid, α-KG plays a direct role in energy production and a wide range of cellular chemical reactions. α-KG provides an energy source, stimulating protein synthesis, inhibiting protein degradation in muscle, and serving as a significant metabolic fuel for gastrointestinal cells.

α-KG promotes osteogenic differentiation of stem cells, increases activity of osteoblasts to promote osteogenesis, and inhibits bone resorption activity of osteoclasts. α-KG in articular cartilage promotes differentiation and maturation of chondrocytes and formation of a cartilage matrix. The protective effect of α-KG on bone has practical value in treatment of abnormal bone loss symptoms in various bone tissue diseases.”

https://www.sciengine.com/ABBS/doi/10.3724/abbs.2025020 “Essential role of the metabolite α-ketoglutarate in bone tissue and bone-related diseases”

A rodent study explored adding α-KG to osteoarthritis treatment:

“Mesenchymal stem cell (MSC) therapy represents a promising treatment strategy for osteoarthritis (OA). Nevertheless, the therapeutic efficacy of MSCs may be attenuated under conditions of cellular senescence or when the available clinical quantity is insufficient. α-Ketoglutarate (AKG) exerts beneficial effects on skeletal tissues and activity of stem cells. The present study was designed to explore the potential of AKG in augmenting viability of MSCs and the potential of their combined utilization in treatment of OA.

AKG plays a crucial role in multiple biological processes. It is involved in regulating stem cell differentiation, exerts anti-apoptotic effects, modulates the body’s immune and inflammatory responses, contributes to muscle and bone development, and is essential for maintaining stability of the cartilage matrix.

Platelet-rich plasma (PRP) has been demonstrated to have protective effects on chondrocytes and can effectively repair damaged cartilage in OA. However, PRP has intractable problems in terms of product quality control and allogeneic application, and its long-term therapeutic effect gradually weakens.

Combining AKG’s regulation of cellular metabolism with the multi-directional differentiation and immunomodulatory functions of MSCs is likely to generate a synergistic effect. This combined treatment modality targets the complex pathological processes of OA, including cartilage damage, inflammatory responses, and extracellular matrix imbalance, in a more comprehensive manner than a single therapy.”

https://www.sciencedirect.com/science/article/pii/S2707368825000032 “The repair effect of α-ketoglutarate combined with mesenchymal stem cells on osteoarthritis via the hedgehog protein pathway”

A rodent study investigated whether α-KG has a role in determining frailty:

“Frailty is an age-related geriatric syndrome, for which the mechanisms remain largely unknown. We performed a longitudinal study of aging female (n = 40) and male (n = 47) C57BL/6NIA mice, measured frailty index, and derived metabolomics data from plasma samples.

We find that frailty related metabolites are enriched for amino acid metabolism and metabolism of cofactors and vitamins, include ergothioneine, tryptophan, and alpha-ketoglutarate, and present sex dimorphism. We identify B vitamin metabolism related flavin adenine dinucleotide and pyridoxate as female-specific frailty biomarkers, and lipid metabolism related sphingomyelins, glycerophosphoethanolamine and glycerophosphocholine as male-specific frailty biomarkers.

We were interested to observe whether metabolite abundance at any specific timepoint was associated with frailty at a future timepoint. Unfortunately, we didn’t observe any metabolites that showed an overall significant association with future FI (FIf) or future devFI (devFIf). When focusing only on the abundance of metabolites at the baseline time point (∼400 days), we found a single metabolite, alpha-ketoglutarate, was negatively associated with both FIf and devFIf.”

https://www.biorxiv.org/content/10.1101/2025.01.22.634160v1.full “Metabolomics biomarkers of frailty: a longitudinal study of aging female and male mice”

Wrapping up with a rodent study adding α-KG to exercise for its effects on depression and learning:

“aKG acts as a prophylactic and antidepressant to effectively counteract social avoidance behaviors by modulating BDNF levels in the hippocampus and nucleus accumbens. Exercise increases aKG levels in the circulation.

In mice, aKG supplementation prolongs lifespan and reduces aging-associated frailty. aKG supplementation also reverses aging in humans as measured by DNA methylation patterns.

aKG functions as a co-factor for epigenetic enzymes. Changes in the intracellular αKG/succinate ratio regulates chromatin modifications, including H3K27me3 and ten-eleven translocation (Tet)-dependent DNA demethylation. The ability of aKG to influence epigenetic status of cells may explain both its prophylactic and anti-depressant effects since transcriptional dysregulation and aberrant epigenetic regulation are unifying themes in psychiatric disorders. This may also explain its ability to differentially regulate BDNF expression in the hippocampus and NAc.

If exercise mediates its effects through aKG, aKG may be a pivotal component of an exercise pill along with lactate and BHB that can serve as both a prophylactic and antidepressant treatment for depression.”

https://www.sciencedirect.com/science/article/pii/S266717432500031X “α-ketoglutarate (aKG) is a circulatory exercise factor that promotes learning and memory recall and has antidepressant properties

Vitamin K2 and your brain

gettingwell4 5+ stars Premium, Cerebrum, Epigenetics, Immune system, Memory, Stress , , ,

A 2025 review linked Vitamin K2‘s effects on vascular health with cognitive function:

“Cardiovascular disease (CVD) is negatively correlated with cognitive health. Arterial stiffness, in particular, appears to be a critical factor in the functional and structural brain changes associated with aging. We review the association between vitamin K and cerebral function, discussing novel developments regarding its therapeutic role in arterial stiffness and cognitive health.

Among the non-invasive measures of vascular stiffness, pulse wave velocity (PWV) is considered the gold standard. PWV measures arterial stiffness along the entire aortic pathway, providing a reliable, feasible, and accurate assessment of vascular health. Arterial stiffness, as measured by PWV, is negatively associated with total brain volume, brain atrophy, and cognitive function. Pathogenic mechanisms responsible for vascular stiffness recently shifted from collagen and elastin to the differentiation of vascular smooth muscle cells to osteoblastic phenotype, which is triggered by oxidative stress and inflammation, membrane mechanotransduction, lipid metabolism, genetic factors, and epigenetics.

Vitamin K-dependent proteins (VKDPs) rely on vitamin K to undergo γ-glutamylcarboxylation, a modification essential for their biological activity. This family of proteins includes hepatic VKDPs such as prothrombin, FVII, FIX, and FX, protein S and protein C as well as extrahepatic VKDPs such as matrix Gla-protein (MGP), which is involved in inhibiting vascular calcification, and osteocalcin, which plays a role in bone mineralization.

Structural differences between K1 and K2 influence their bioavailability, absorption, bioactivity, and distribution within tissues. Compared to vitamin K1, the K2 subtype menaquinone-7 (MK-7) has a significantly longer half-life, accumulates more effectively in blood, and exhibits greater biological activity, particularly in facilitating the carboxylation of extrahepatic VKDPs. Circulating dephosphorylated, uncarboxylated Matrix Gla protein (dp-ucMGP), a marker of extrahepatic vitamin K deficiency, could represent a novel therapeutic target for mitigating both arterial stiffness and cognitive decline.

Vascular calcification and arterial stiffness may represent pathophysiological mechanisms underlying the onset and progression of cognitive decline. Vitamin K deficiency is a key determinant of arterial health and, by extension, may influence cognitive function in the elderly.

To elucidate potential therapeutic benefits of MK-7 supplementation on cognitive function, future randomized controlled trials (RCTs) are needed. These trials should focus on using optimal dosages (>500 μg/day), ensuring long follow-up periods, and utilizing the most bioactive form of vitamin K (MK-7).”

https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2024.1527535/full “The role of vitamin K2 in cognitive impairment: linking vascular health to brain health”

A coauthor Dr. Katarzyna Maresz took time on her weekend to answer a few questions:

1. Regarding the second paper of Part 2 of Vitamin K2 – What can it do?:

Hello Dr. Maresz. Did this trial ever happen? “Effects of Combined Vitamin K2 and Vitamin D3 Supplementation on Na[18F]F PET/MRI in Patients with Carotid Artery Disease: The INTRICATE Rationale and Trial Design” I haven’t seen a followup mention of it since 2021.

“Hello. The study never started. The capsules were produced for the study, but the research center experienced delays. Unfortunately, I’m afraid it won’t proceed. Regarding studies on aortic stenosis and vitamin K2, BASIC II has been completed, and the data from this pilot study are currently under analysis. (https://pubmed.ncbi.nlm.nih.gov/29561783/). There is also published study with K1: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.116.027011

2. Thank you! In your recent review of cognitive function and K2 (above), what influenced the heuristic that a >500 mcg K2 dose should be pursued in future RCTs?

“The optimal vitamin K dosage depends on the target population. Research in kidney patients has shown that 460 mcg daily was insufficient, that is why have hypothesis that at least 500 mcg should be used. The ongoing VIKIPEDIA study is using 1,000 mcg daily in peritoneal dialysis patients. In healthy young individuals, 180-360 mcg was effective in improving vitamin K status (British Journal of Nutrition (2012), 108, 1652–1657) . However, a one-year clinical study found that 180 mcg daily was sufficient for women but not for men. Additionally, older adults and individuals with metabolic disorders may require higher doses for optimal benefits. So it is pretty complicated situation. We do not have good marker of extrahepatic K status. dp-ucMGP seems to be valuable from CV perspective.”

3. Regarding Fat-soluble vitamin competition:

Thank you again Dr. Maresz! Would any consideration be given to dosing K2 separately from dosing another fat-soluble vitamin? A 2015 in vitro study found that vitamins D, A, and E outcompeted K1 intake when simultaneously dosed. I inferred from the one capsule of D3-K2 produced for the canceled trial that isn’t that much of a problem with K2?

“You are right, the key findings suggest that vitamin D, E, and K share common absorption pathways, leading to competitive interactions during uptake. However, I’m afraid we do not have human data. The majority of studies have focused on vitamin K2 alone. Recent research combining K2 and D3 showed an improvement in vitamin K status. Example: https://pubmed.ncbi.nlm.nih.gov/35465686/ or increase in D level: https://pubmed.ncbi.nlm.nih.gov/39861434/. We do not know if VKDP activation or absorption of D would be more effective if K2 were not supplemented with D3 at the same time. Unfortunately, I doubt anyone will fund such a study, as clinical trials are very expensive. In vitro data will always raise questions regarding their relevance to human physiology. In my opinion, for patients to fully benefit from optimal vitamin K status, vitamin D levels should also be optimized, as both have synergistic effects.”

Epigenetic clock analysis of a clinical trial

gettingwell4 4-5 stars Advanced knowledge, Epigenetics, Memory, Stress , , ,

A 2025 paper performed post-hoc epigenetic clock analyses of a supplement and exercise clinical trial completed earlier this decade:

“We report results of a post hoc analysis among 777 participants of the DO-HEALTH trial on the effect of vitamin D (2,000 IU per day) and/or omega-3 (1 g (330 mg EPA plus 660 mg DHA from marine algae) per day) and/or a home exercise program (a strength-training exercise program performed for 30 min three times per week) on four next-generation DNA methylation (DNAm) measures of biological aging (PhenoAge, GrimAge, GrimAge2 and DunedinPACE) over 3 years. Omega-3 alone slowed the DNAm clocks PhenoAge, GrimAge2 and DunedinPACE, and all three treatments had additive benefits on PhenoAge.

Inclusion criteria were age 70 years and older, living at home, having no major health events (no cancer or myocardial infarction) in the 5 years before enrollment, having sufficient mobility to visit the study centers without help and having good cognitive function with a Mini-Mental State Examination score of at least 24. 777 provided consent for these analyses and had samples available after the application of the exclusion criteria. This group of individuals formed our analysis sample, which had the following characteristics: 59% were women; the mean age at baseline was 75 years; 30% had 25-hydroxyvitamin D (25(OH)D) levels of <20 ng ml−1; 53% were healthy agers as defined in the Nurses’ Health Study (free of major chronic diseases, disabilities, cognitive impairments and mental health limitations); and 88% were physically active (29% were active one to three times per week, and 59% were active more than three times per week). The Swiss participant subgroup represents a healthier and more active subgroup within the total DO-HEALTH population.

Overall, from baseline to year 3, standardized effects ranged from 0.16 to 0.32 units (2.9–3.8 months). In summary, our trial indicates a small protective effect of omega-3 treatment on slowing biological aging over 3 years across several clocks, with an additive protective effect of omega-3, vitamin D, and exercise based on PhenoAge.”

https://www.nature.com/articles/s43587-024-00793-y “Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial”

These epigenetic clock measurements of a subset of trial subjects was interesting, although I didn’t find it particularly relevant to what I do. I take twice as much Vitamin D and omega-3s everyday, do resistance exercises once or twice a week whenever I’ve recovered from the previous session, walk a few miles on the beach if the weather is nice, and other things.

I don’t bother with epigenetic clock measurements anymore because the free one (PhenoAge) is too variable to be personally accurate. For other clocks, it would be meaningless if all I got was a 2-3 month improvement over a three year period like this trial. Studies usually find that the most deficient subjects at the beginning are the ones that show the greatest improvements with effective treatments. Unhealthiness on any epigenetic clock parameter probably wouldn’t be my starting point, so I may not show even a one-month improvement over three years.

Dr. Goodenowe offered his opinion on the paper:

“DHA is a polyunsaturated fatty acid that is essential for maintaining youthful fluidity of the body’s membranes. While our bodies can make DHA from the essential omega-3 dietary fatty acid, as we get older, our ability to make DHA decreases and oxidative stress on our bodies increases. These two factors contribute to our membranes becoming stiffer and less pliable as we age, in other words, ‘older.’

Because getting older and losing function appear to go hand in hand, we equate aging with a loss of function. As such, we think that aging causes this loss of function, like a disease. Instead, the opposite is true, and it’s the loss of function that causes aging. To slow aging you need to focus on maintaining function.”

https://www.prevention.com/health/a63850396/vitamin-exercise-boost-longeivty-study/ “Scientists Find Taking This Vitamin Boosts Longevity, Add Years to Your Life”

Prevention magazine’s editors need to better proof their writers’ work before it gets published. Unlike the headline, the trial had nothing to do with adding years to human lifespan.

Broccoli antihypertensive peptides

gettingwell4 4-5 stars Advanced knowledge, Epigenetics, Stress

This 2025 rodent cell study investigated effects of broccoli peptides:

“ACE is a pivotal enzyme that has a regulatory effect on blood pressure in human renin-angiotensin system (RAS). Inhibiting ACE activity can reduce production of angiotensin II (Ang II), which binds to receptors on the vascular wall, causing vasoconstriction.

Development of natural ACE inhibitors with low side effects is an urgent need for cardiovascular therapy. Many natural angiotensin-converting enzyme inhibitory (ACEI) peptides have been widely studied. However, their stability in vivo is poor in most cases.

In this study, peptides were initially digested from broccoli in vitro, and absorption was simulated by Caco2 cells transport and then analyzed by peptideomics and molecular docking. ACEI activity of broccoli crude peptide increased after digestion.

Subsequently, mechanisms were verified using a high glucose-induced vascular smooth muscle cells (VSMCs) dysfunction model. Five peptides not only inhibited proliferation, migration, and apoptosis of VSMCs by inhibiting ERK and p38 MAPK phosphorylation, but also restrained the activities of ACE and AT1R, prominently reducing Ang II levels within VSMCs under high glucose.

This research provides valuable insights into the production of novel ACEI peptides derived from broccoli protein, and offers directions for utilization of these antihypertensive peptides in health applications.”

https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1528184/full “In vitro gastrointestinal digestion simulation screening of novel ACEI peptides from broccoli: mechanism in high glucose-induced VSMCs dysfunction”

Coffee compound effects

gettingwell4 4-5 stars Advanced knowledge, Epigenetics, Immune system, Neurochemicals, Serotonin, Stress, Telomeres , ,

Three papers continue Polyphenol Nrf2 activators themes starting with a 2025 review of chlorogenic acid:

“Chlorogenic acid may comprise between 70 and 350 mg per cup of coffee. Chlorogenic acid can reduce reactive oxygen species (ROS) levels via the upregulation of antioxidant enzymes, decreasing oxidative stress/damage due to the action of adaptive hormetic mechanisms. There is also a substantial literature of hormetic dose responses for metabolites of chlorogenic acid, such as caffeic acid and ferulic acid.

Chlorogenic acid-induced hormetic biphasic dose responses in a spectrum of experimental designs:

  1. Responses to direct exposures in a range of cell types;
  2. Preconditioning experiments in which a prior dose of chlorogenic acid protected against a subsequent stressor agent;
  3. Studies that included direct exposure, showing hormesis dose responses and then selecting the optimal hormetic dosage as a preconditioning treatment to protect against a subsequent exposure to a toxic agent; and
  4. A mixed group of experiments in which preconditioning was conducted, including several neuronal cellular models, all showing protection against the subsequent exposure to the toxic agent.

However, in the context of translating experimental data to clinical relevance, the concentrations employed in the majority of the in vitro studies with chlorogenic acid far exceeded transitory peak levels, even in heavy coffee drinkers (i.e., approximately 3 μM). In addition to the use of unrealistically high chlorogenic acid concentrations, exposures were prolonged, ranging from 1 to 3 days. These studies are of limited relevance to humans, a similar concern raised by other researchers involved with polyphenol research.


The present paper has framed the hypothesis that key coffee constituents, such as chlorogenic acid, show hormetic effects in a range of cell types and endpoints. Chlorogenic acid may affect some of the health benefits of coffee drinking via its role in GI tract health and beneficial brain-gut interaction.”

https://www.sciencedirect.com/science/article/abs/pii/S0009279724004897 “Do the hormetic effects of chlorogenic acid mediate some of the beneficial effects of coffee?” (not freely available) Thanks to Dr. Evgenios Agathokleous for providing copies of this and the following paper.

A 2024 review by the same research group was on hormetic effects of caffeic acid:

“Caffeic acid is a polyphenol present in numerous fruits and vegetables, especially in coffee. Diets contain about 5–10 to 50 milligrams per day of caffeic acid while coffee ingestion provides about another 250–600 milligrams per day. For the moderate to heavy coffee drinker this would result in an ingestion of about 600–1000 milligrams of caffeic acid from food and coffee consumption.

The present paper evaluates whether caffeic acid may act as an hormetic agent, mediating its chemoprotective effects as has been shown for related agents, such as rosmarinic acid, ferulic acid, and chlorogenic acid. Caffeic acid protective effects were mediated via the upregulation of a series of antioxidant enzymes related to activation of Nrf2.

Caffeic acid enhanced the lifespan of C. elegans along with similar observations for rosmarinic acid that can be hydrolyzed to caffeic acid. Several hundred plant-based agents can enhance lifespan in experimental models such as C. elegans, and there is a competition to find the most effective agents with potential commercial applications.

Hormetic effects typically show a 30 to 60% stimulation above control. This is far below the 2 to 3-fold greater than control detection limit for statistical significance based on human variability/bioplasticity and are often reported as false negatives.

A weight-of-evidence approach was proposed based on multiple in vivo and in vitro test results to derive a study design strategy to increase detection of hormetic effects within the clinical trial framework. Such research should explore hormetic based interactions linking protective catabolic-based adaptive responses with activation and regulation of anabolic mediated hormetic growth effects.”

https://www.tandfonline.com/doi/full/10.1080/19390211.2024.2410776 “Caffeic Acid: Numerous Chemoprotective Effects are Mediated via Hormesis” (not freely available)

A 2024 review provided an overall picture of coffee compounds’ cardiometabolic effects:

“This review provides a comprehensive synthesis of longitudinal observational and interventional studies on the cardiometabolic effects of coffee consumption.

  • Findings indicate that while coffee may cause short-term increases in blood pressure, it does not contribute to long-term hypertension risk.
  • There is limited evidence indicating that coffee intake might reduce the risk of metabolic syndrome and non-alcoholic fatty liver disease.
  • Coffee consumption is consistently linked with reduced risks of type 2 diabetes (T2D) and chronic kidney disease (CKD), showing dose-response relationships.
  • The relationship between coffee and cardiovascular disease is complex, showing potential stroke prevention benefits but ambiguous effects on coronary heart disease.
  • Moderate coffee consumption, typically ranging from 1 to 5 cups per day, is linked to a reduced risk of heart failure, while its impact on atrial fibrillation remains inconclusive. Coffee consumption is associated with a lower risk of all-cause mortality, following a U-shaped pattern, with the largest risk reduction observed at moderate consumption levels.
  • Except for T2D and CKD, Mendelian randomization studies do not robustly support a causal link between coffee consumption and adverse cardiometabolic outcomes.

Potential beneficial effects of coffee on cardiometabolic health are consistent across age, sex, geographical regions, and coffee subtypes and are multi-dimensional, involving antioxidative, anti-inflammatory, lipid-modulating, insulin-sensitizing, and thermogenic effects. Based on its beneficial effects on cardiometabolic health and fundamental biological processes involved in aging, moderate coffee consumption has the potential to contribute to extending healthspan and increasing longevity.”

https://pmc.ncbi.nlm.nih.gov/articles/PMC11493900 “Coffee consumption and cardiometabolic health: a comprehensive review of the evidence”

Nrf2 regulation

gettingwell4 5+ stars Premium, Cortisol, Epigenetics, Glutamate, Neurochemicals, Stress

This 2025 review explored what’s known so far about Nrf2 post-translational regulators:

“Nrf2 is controlled at multiple levels, including epigenetic, transcriptional, translational, and post-translational. The focus of this review is on proteins that control Nrf2 at the post-translational level because in normal cells they are of preeminent importance.

We outline mechanisms by which multiple E3 ubiquitin ligases act to repress Nrf2 expression, how derepression of Nrf2 (and induction of its target genes) by oxidative stressors occurs, and why tissue injury and endoplasmic reticulum stress downregulate Nrf2. This update also explains how Nrf2 is embedded in thiol biochemistry, and outlines signaling pathways and endogenous signaling molecules that control its activity.

Nrf2 not only positively controls the basal and/or inducible expression of a substantial number of genes in all tissues but also downregulates many genes. Estimates of the number of antioxidant/electrophile-responsive element (ARE/EpRE)-driven genes that are positively regulated by Nrf2 vary from several hundred to >2000 depending on the experimental method, species, cell type, physiology, age, sex, diet, and the magnitude of the change that is deemed to be significant.

Induction of ARE/EpRE-driven genes allows adaptation to oxidative, electrophilic, and inflammatory stress. Nrf2 positively regulates clusters of genes encoding proteins classed broadly as antioxidant, drug-, heme-, and iron-metabolizing, pentose phosphate pathway, NADPH-generating, and autophagy-related, as well as fatty acid oxidation enzymes, lipases, transcription factors, and Keap1.

Genes that are negatively regulated by Nrf2 include those encoding the cytokines IL-1β and IL-6, myosin light-chain kinase (MYLK), and NADPH oxidase 4 (NOX4). Nrf2 also regulates some microRNAs, which represents another mechanism by which Nrf2 can downregulate the expression of genes such as those encoding collagens 1A2, 3A1, and 5A1, heat shock protein 47, fibronectin, and elastin. In addition, several lipogenesis-related genes such as fatty acid synthase 1 (FASN1) and acetyl-CoA carboxylase 1 (ACC1), stearoyl-CoA desaturase (SCD1), and fatty acid elongase 6 (ELOVL6) are downregulated upon Nrf2 activation, particularly under conditions of lipid overload. Given that lipogenesis is a highly NADPH-consuming process, it seems that Nrf2 activation redirects NADPH consumption from lipid synthesis towards redox reactions, although the mechanisms underlying the negative regulation of these genes are incompletely understood.

de novo synthesized Nrf2 upon Keap1 inactivation enables a rapid increase of levels of the transcription factor in response to metabolic changes and environmental challenges, allowing cells to adapt and restore homeostasis.”

https://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(24)00282-2 “Regulating Nrf2 activity: ubiquitin ligases and signaling molecules in redox homeostasis”

This review’s primary audience is other researchers, and it ended with 15 outstanding items that Nrf2 research hasn’t yet adequately addressed.

Reversing hair greying, Part 2

gettingwell4 4-5 stars Advanced knowledge, Cortisol, Epigenetics, Neurochemicals, Stress, Testosterone , ,

Three papers that cited the 2021 Reversing hair greying study, starting with a 2024 rodent study:

“External treatment with luteolin, but not that with hesperetin or diosmetin, alleviated hair graying in model mice. Internal treatment with luteolin also mitigated hair graying.

Both treatments suppressed the increase in p16ink4a-positive cells in bulges [senescent keratinocyte stem cells (KSCs)]. Both treatments also suppressed decreases in expression levels of endothelins in KSCs and their receptor (Ednrb) in melanocyte stem cells (MSCs), and alleviated hair graying in mice.”

https://www.mdpi.com/2076-3921/13/12/1549 “Anti-Graying Effects of External and Internal Treatments with Luteolin on Hair in Model Mice”

This study treated subjects internally and externally with luteolin and hesperetin, which are ranked #7 (effective treatment) and #14 (not an effective treatment) per Nrf2 activator rankings. I wonder what these researchers would have found if they used the #1 ranked Nrf2 activator, sulforaphane.

A 2024 review managed to cover the Nrf2 activation subject without mentioning sulforaphane:

“Certain types of hair graying can be prevented or treated by enhancing MSC maintenance or melanocyte function, reducing oxidative stress, and managing secretion and action of stress hormones.

Tactical approaches to pursue this goal may include a selective activation of the p38 MAPK–MITF axis, enhancing cellular antioxidant capacity through activating NRF2, and modulating the norepinephrine–β2AR–PKA signaling pathway.”

https://www.mdpi.com/2076-3417/14/17/7450 “Intrinsic and Extrinsic Factors Associated with Hair Graying (Canities) and Therapeutic Potential of Plant Extracts and Phytochemicals”

This reviewer also avoided citing the 2021 Sulforaphane and hair loss, although hair loss was mentioned multiple times. I suspect that institutional politics was involved, as both papers are from South Korea.

Reference 32 of this review was a 2023 review that covered mainly unintentional hair greying reversal as a side effect noted when people had pharmaceutical treatments for various diseases:

“Hair graying is a common and visible sign of aging resulting from decreased or absence of melanogenesis. It has long been thought that reversal of gray hair on a large scale is rare. However, a recent study reported that individual gray hair darkening is a common phenomenon, suggesting the possibility of large-scale reversal of gray hair.

All these treatments rely on the presence of a sufficient population of active McSCs. Maintaining a healthy population of McSCs is also an urgent problem that needs to be addressed.”

https://www.ijbs.com/v19p4588.htm “Reversing Gray Hair: Inspiring the Development of New Therapies Through Research on Hair Pigmentation and Repigmentation Progress”

I published A hair color anecdote two months into eating broccoli sprouts every day when I first noticed dark hair growing in. Since it’s been over 4 years that I’ve continued eating broccoli sprouts daily, I think it’s alright to stop referring to my continuing reversal of hair greying as an anecdote.

But it was apparently too late to address hair loss, which started before I turned 30. So now you know what to do. 🙂

Nrf2 activator rankings

gettingwell4 5+ stars Premium, Epigenetics, Stress ,

A 2024 cell study compared and contrasted findings of previous plant compound Nrf2 inducer studies with a newer assay type:

“Various plants have been reported to contain compounds that promote transcriptional activity of Nuclear factor erythroid 2-related factor 2 (Nrf2) to induce a set of xenobiotic detoxifying enzymes, such as NAD(P)H-quinone acceptor oxidoreductase 1 (NQO1), via the antioxidant response element (ARE). An ARE luciferase reporter assay was recently developed to specifically assess Nrf2 induction potency of compounds.

33 compounds were sorted in the order of their transcriptional activity of Nrf2. CD value is the concentration of a compound required to double the basal activities of individual enzymes or luciferase activity.

nrf2 induction

This study is the first to examine consistency of the transcriptional activity of Nrf2 evaluated using ARE reporter and NQO1 assays for multiple compounds. Future comparisons of CD values by each assay across cell types may be used to demonstrate consistency between the assays, as well as to reveal the factors that influence Nrf2 induction potency.”

https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-024-07038-6 “Nrf2 induction potency of plant-derived compounds determined using an antioxidant response element luciferase reporter and conventional NAD(P)H-quinone acceptor oxidoreductase 1 activity assay”

A 2019 ranking of sulforaphane with 18 other Nrf2 activators was curated in Part 2 of Rejuvenation therapy and sulforaphane, and pointed out bioavailability differences:
OMCL2019-2716870.006

It [sulforaphane] is not only a potent Nrf2 inducer but also highly bioavailable [around 80%], so that modest practical doses can produce significant clinical responses. Other Nrf2 activators [shown in the above image] not only lack potency, but also lack the bioavailability to be considered as significant intracellular Nrf2 activators.”

This study attempted to explain differences in the two assay findings with numerous “may” and “could” statements. Okay.

But if you want to activate your body’s endogenous detoxification and antioxidant systems with a natural plant compound, sulforaphane remains the number one choice.

PXL_20241223_185836159

TFEB and autophagy

gettingwell4 2-3 stars Required further work, Stress ,

Two 2024 papers that cited Precondition your defenses with broccoli sprouts, starting with an in vitro study of influences on auditory cell function:

“Although various studies have focused on the effect of oxidative stress on the inner ear as an inducer of age-related hearing loss (ARHL), there are no effective preventive approaches for ARHL.

We focused on the function of TFEB and the impact of intracellular ROS as a potential target for ARHL treatment in a NaAsO2-induced auditory premature senescence model. Our results suggested that short exposure to NaAsO2 leads to DNA damage, lysosomal damage and mitochondrial damage in auditory cells, triggering temporary signals for TFEB transport into the nucleus and, as a result, causing insufficient autophagic flux and declines in lysosomal function and biogenesis and mitochondrial quality.

41420_2024_2139_Fig6_HTML

This is the first report to indicate that the inactivation of TFEB directly causes oxidative stress (NaAsO2)-induced premature auditory senescence and SASP induction via decreases in autophagic flux and lysosomal dysfunction, with a lowered pH at the transcriptional level and, as a consequence, ROS production with decreasing mitochondrial quality in auditory cells. The activator of TFEB might have a pivotal antiaging effect in the inner ear.”

https://www.nature.com/articles/s41420-024-02139-4 “Premature senescence is regulated by crosstalk among TFEB, the autophagy lysosomal pathway and ROS derived from damaged mitochondria in NaAsO2-exposed auditory cells”

These researchers used exposure concentrations and durations that had no relevance to humans. Human irrelevance made it difficult to assess the above graphic that shows both TFEB activation and inactivation as stress-related. “No effective preventive approaches for ARHL” was asserted as a given, although “TFEB activation via transport into the nucleus contributes to anti-senescence activity in auditory cells and represents a new therapeutic target for ARHL” was also stated.

Just like the two papers in Eat broccoli sprouts for your hearing, preconditioning’s importance wasn’t investigated. So this study didn’t have findings about how mild TFEB activation or inactivation might precondition auditory cells for other stress that might damage hearing.

Next is a review of muscle regeneration and autophagy:

“Satellite cells, also known as muscle stem cells when activated, are essential for muscle repair. These adult stem cells typically remain in a dormant state. In response to tissue injury, these cells are rapidly activated and divided to generate new stem cells, which proliferate to form myoblasts, which further differentiate into myocytes to repair damaged muscle tissue. However, muscle regeneration can be significantly impaired under various conditions due to dysfunctional satellite cell activity.

mTORC1 activity is suppressed during amino acid starvation, leading to autophagy activation. Under these conditions, TFEB, TFE3, and MITF translocate to the nucleus, where they enhance the transcription of genes involved in autophagy and lysosomal function. When nutrients are abundant, mTORC1 suppresses autophagy. This inhibition ensures that resources are directed toward growth and proliferation rather than cellular recycling.

Chronic injuries are typically associated with sustained metabolic or oxidative stress, leading to prolonged or impaired autophagy. While autophagy serves a compensatory and beneficial role in acute injuries, its role in chronic muscle diseases is more complex. On the one hand, autophagy alleviates oxidative stress and mitigates aging. On the other hand, dysregulated autophagy may contribute to muscle fibrosis and loss of muscle mass.

The function of autophagy varies across different stages of satellite cell activity. Autophagy:

  1. Maintains cellular homeostasis by clearing damaged organelles.
  2. Preserves the number of satellite cells by antagonizing apoptosis.
  3. Sustains the quiescence of satellite cells by reducing reactive oxygen species (ROS).
  4. Promotes the activation of satellite cells by supplying energy.
  5. Facilitates the differentiation of satellite cells by mitochondrial remodeling.”

ijms-25-11901-g003-550

https://www.mdpi.com/1422-0067/25/22/11901 “Autophagy in Muscle Regeneration: Mechanisms, Targets, and Therapeutic Perspective”

I’ve curated a few other of the 110 papers that cited the 2020 “Sulforaphane activates a lysosome-dependent transcriptional program to mitigate oxidative stress” over the years, to include:

Sulforaphane’s effects on autism and liver disease;

Bridging Nrf2 and autophagy; and

Eat broccoli sprouts to maintain your cells.

Polyphenol Nrf2 activators

gettingwell4 2-3 stars Required further work, Acetylcholine, Amygdala, Cerebrum, Cortisol, Dopamine, Epigenetics, Glutamate, Hippocampus, Hypothalamus, Immune system, Limbic system, Memory, Neurochemicals, Oxytocin, Serotonin, Stress, Vasopressin , , , , ,

Two 2024 reviews by the same group that published Sulforaphane in the Goldilocks zone investigated dietary polyphenols’ effects as “hormetic nutrients”:

“Polyphenols display biphasic dose–response effects by activating at a low dose the Nrf2 pathway resulting in the upregulation of antioxidant vitagenes [see diagram]. We aimed to discuss hormetic nutrients, including polyphenols and/or probiotics, targeting the Nrf2 pathway and vitagenes for the development of promising neuroprotective and therapeutic strategies to suppress oxidative stress, inflammation and microbiota deregulation, and consequently improve cognitive performance and brain health.

antioxidants-13-00484-g001

Hormetic nutrition through polyphenols and/or probiotics targeting the antioxidant Nrf2 pathway and stress resilient vitagenes to inhibit oxidative stress and inflammatory pathways, as well as ferroptosis, could represent an effective therapy to manipulate alterations in the gut microbiome leading to brain dysfunction in order to prevent or slow the onset of major cognitive disorders. Notably, hormetic nutrients can stimulate the vagus nerve as a means of directly modulating microbiota-brain interactions for therapeutic purposes to mitigate or reverse the pathophysiological process, restoring gut and brain homeostasis, as reported by extensive preclinical and clinical studies.”

https://www.mdpi.com/2076-3921/13/4/484 “Hormetic Nutrition and Redox Regulation in Gut–Brain Axis Disorders”

I’m not onboard with this study’s probiotic assertions because most of the cited studies contained unacknowledged measurement errors. Measuring gut microbiota, Part 2 found:

“The fecal microbiome does not represent the overall composition of the gut microbiome. Despite significant roles of gut microbiome in various phenotypes and diseases of its host, causative microbes for such characteristics identified by one research fail to be reproduced in others.

Since fecal microbiome is a result of the gut microbiome rather than the representative microbiome of the GI tract of the host, there is a limitation in identifying causative intestinal microbes related to these phenotypes and diseases by studying fecal microbiome.”

These researchers also erroneously equated isothiocyanate sulforaphane’s Nrf2-activating mechanisms with polyphenols activating Nrf2.

This research group did better in clarifying polyphenols’ mechanisms in a review of hormetic dose-response effects of the polyphenol rosmarinic acid:

“This article evaluates whether rosmarinic acid may act as a hormetic agent, mediating its chemoprotective effects as has been shown for similar agents, such as caffeic acid, a derivative of rosmarinic acid.

Rosmarinic acid enhanced memory in institute of cancer research male mice in the Morris water maze (escape latency).

untitled

Of importance in the evaluation of rosmarinic acid are its bioavailability, metabolism, and tissue distribution (including the capacity to affect and/or cross the BBB and its distribution and half-life within the brain). In the case of polyphenols, including rosmarinic acid, they are typically delivered at low doses in the diet and, in most instances, they do not escape first-pass metabolism, with the prominent chemical forms being conjugates of glucuronides and sulfates, with or without methylation.

These conjugated metabolites are chemically distinct from the parent compound, showing considerable differences in size, polarity, and ionic form. Their biological actions are quite different from the parent compound.

Bioavailability studies reveal that maximum concentrations in plasma typically do not exceed 1 µM following consumption of 10–100 mg of a single phenolic compound, with the maximum concentration occurring typically less than 2 h after ingestion, then dropping quickly thereafter. In the case of the in vitro studies assessed herein, and with few exceptions, most of the studies employed concentrations >10 µM with some studies involving concentrations in the several hundred µM range, with the duration of exposure typically in the range of 24–72 h, far longer duration than the very short time interval of a few minutes to several hours in human in vivo situations.

We strongly recommend that all experiments using in vitro models to study biological responses to dietary polyphenols use only physiologically relevant flavonoids and their conjugates at appropriate concentrations, provide evidence to support their use, and justify any conclusions generated. When authors fail to do this, referees and editors must act to ensure that data obtained in vitro are relevant to what might occur in vivo.”

https://www.degruyter.com/document/doi/10.1515/med-2024-1065/html “The chemoprotective hormetic effects of rosmarinic acid”

An elevator pitch for plasmalogen precursors

gettingwell4 4-5 stars Advanced knowledge, Acetylcholine, Dopamine, Epigenetics, Glutamate, Hippocampus, Immune system, Limbic system, Lower brain, Memory, Neurochemicals, Serotonin, Stress, Thalamus , , ,

An excerpt from the latest video at Dr. Goodenowe’s Health Matters podcast, Episode 7 “The Truth about Parkinson’s”, starting at 50:30:

“What’s exciting about this community medicine focus that we’ve switched to which basically says: How do we develop technologies in a way that they can be incorporated into a community model versus a pharmaceutical drug model? People can actually do I would say self-experiment just the way you self-experiment with your own diet because these are fundamentally dietary nutrition molecules.

Could you give me an elevator pitch because there are probably people listening who are thinking what is this plasmalogen precursor and for sure how is it having this dramatic effect?

Plasmalogens are the most important nutrient that nobody knows about. Normally you don’t know about it because the body is usually pretty good at making them. What makes plasmalogens unique is that your body makes them kind of like cannon fodder, the first group of people that go into war. Your body throws them out for destruction. They absorb oxidative stress and get destroyed in the process.

They’re stored in your cell membranes. 50% of the membranes of your heart are these plasmalogen molecules. When your heart gets inflamed, what your heart does is it dumps these plasmalogens out of its membranes to douse the flame of inflammation. After inflammation is under control, your body naturally builds these things back up again.

But if you have an inability to make enough plasmalogens, these inflammation events knock you down and keep you down. So plasmalogen precursors are critical for maintaining high levels of plasmalogens across your body, not just in your brain (30% of the lipids in your brain) but in your heart, your lungs, your kidneys.”

PXL_20241117_185248742~2

Do broccoli sprouts help treat colonic inflammation?

gettingwell4 4-5 stars Advanced knowledge, Epigenetics, Immune system, Stress

A 2024 human study investigated broccoli sprouts’ effects as an adjunct to ulcerative colitis treatment:

“A dietary approach with sulforaphane (SFN)-rich broccoli sprouts (BS) mitigates colonic inflammation in human ulcerative colitis (UC) patients treated with mesalazine. Subjects were instructed to take 20 g of raw BS or alfalfa sprouts (AS) daily for 8 weeks, with BS containing 4.4 mg/g glucoraphanin, a precursor of sulforaphane, and AS containing no glucoraphanin.

Our findings indicate that the positive effects of SFN-rich BS may be driven by activation of the Nrf2-dependent antioxidant system, which helps combat chronic oxidative stress.

broccoli sprouts and ulcerative colitis

Instead of using glucoraphanin tablets, we used raw BS in our study. Most of the glucoraphanin in BS is converted to biologically active SFN by myrosinase activity in raw BS during chewing BS in the oral cavity. The rest of the glucoraphanin is converted into biological active SFN by myrosinase activity in intestinal microbiota.

Oral intake of BS induces much higher concentrations of systemic SFN compared to taking the same amount of oral glucoraphanin tablets. Another clinical trial using pure SFN, such as via glucoraphanin tablets, instead of using BS, must be conducted.”

https://www.ffhdj.com/index.php/ffhd/article/view/1440/4044 “Dietary intake of sulforaphane-rich broccoli sprouts decreases fecal calprotectin levels in patients with ulcerative colitis”

This study’s daily 20 grams of broccoli sprouts and 88 mg (4.4 mg x 20) glucoraphanin is about what I take, with red cabbage sprouts (which also contain glucoraphanin) and mustard sprouts comprising the other two thirds of total 60-65 grams. Sulforaphane amounts weren’t calculated, as they depend on whether sprouts were eaten with other foods (I’ve eaten them alone since Week 19), how thoroughly sprouts were chewed (I chew each mouthful for at least a minute before swallowing), the presence of certain gut microbiota, sprout age, and other factors.

PXL_20241006_161510628