Author: gettingwell4

Broccoli sprouts’ immune effects

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

Two 2021 papers, with the first’s subject being sulforaphane’s immune effects:

“Effects of sulforaphane (SFN) on immune response generate scientific interest because of its bioavailability, which is much higher than other phytochemicals, and its capacity to induce Nrf2 target genes. Clinical trials suggest that sulforaphane produces favorable results in cases where pharmaceutical products fail.

SFN exhibits the highest bioavailability among well-known antioxidant phytochemicals, such as quercetin (20-fold higher) and curcumin (80-fold higher). SFN confers a high potential to be used either as a nutraceutical to improve health status, or as pharmaceutical to treat disease states.

molecules-26-00752-g001

Sulforaphane exerts a pleiotropic effect on immunological response, and the final effect depends on cell type.

  • In lymphocyte T-cells, SFN induces ROS production, GSH depletion, and repression of inflammatory cytokines, resulting in suppression of immune and inflammatory responses.
  • In monocytes and macrophages, SFN stimulates immune response by inducing Nrf2, thus triggering antioxidant and anti-inflammatory responses.”

https://www.mdpi.com/1420-3049/26/3/752/htm “Potential of Sulforaphane as a Natural Immune System Enhancer: A Review”

A second study was Fertilization and Pre-Sowing Seed Soaking Affect Yield and Mineral Nutrients of Ten Microgreen Species:

“Ten tested microgreen species [amaranth, arugula, basil, broccoli, red cabbage, Daikon radish, kale, kohlrabi, mustard, and green pea] in this study varied in fresh and dry shoot weights, shoot height, and mineral nutrient concentrations.”

This study grew sprouts for 6 – 18 days before harvesting. Its study design didn’t require sampling along the way to discover informative compositional changes, as did 2020’s 3-day-old broccoli sprouts have the optimal yields and Broccoli sprout compounds include sinapic acid derivatives.

Their supplier was the same as I used for broccoli and red cabbage seeds. No endorsement is intended.

I’d rather use an unknown broccoli variety than this study’s broccoli cultivar, Waltham 29. It was found to be relatively glucoraphanin-deficient when measured in a 2004 study referenced in Tailoring measurements for broccoli sprouts, 32nd of 34 tested.

Received these today:

PXL_20210424_191628875

I’ve asked for clarification of the red cabbage seed variety I received. Not sure what “Agnostic” means in a “Red Cabbage Microgreen – Agnostic” context. 🙂

Mustard and red cabbage sprouting will follow Improving healthy compounds of broccoli sprouts efforts, minus that study’s laboratory setup and duration. I expect synergistic effects from handling both species’ sprouts with my protocol for microwaved 3-day-old broccoli sprouts.

Benefits of eating fermentable fiber

gettingwell4 2-3 stars Required further work, Epigenetics, Immune system, Memory, Stress

This 2021 review subject was effects of short-chain fatty acids produced by gut microbiota:

“SCFAs are the main players in the interplay between diet, microbiota, and health. SCFAs contribute to intestinal homeostasis and regulation of energy metabolism.

SCFAs regulate the blood–brain barrier and neuroimmunoendocrine functions. During gestation, SCFAs can cause epigenetic imprinting and protect against allergic airway disease.

gr3_lrg

Fiber reaching the colon is anaerobically fermented by gut bacteria, which produce SCFAs. Nondigestible polysaccharides are found in plant cell walls, and are further classified into soluble and nonsoluble dietary fibers.

A role for SCFAs in histone modification of tissues in the body was definitively shown by dietary supplementation of germ-free mice with microbially produced acetate, propionate, and butyrate. These SCFAs increased acetylation of histone H4 and H3 in a tissue-specific fashion.

Most research to date has focused on butyrate but unlike acetate and propionate, it is typically present in undetectable or very low concentrations in the body. SCFAs appear to influence health through three principal mechanisms:

  1. Altering levels of HAT [histone acetyltransferase] and HDAC [histone deacetylase] activity;
  2. Signaling by specific fatty acid-sensing GPCRs [G-protein-coupled receptors]; and
  3. Anti-inflammatory mechanisms in the periphery and tissues due to the first two mechanisms.”

https://www.cell.com/trends/microbiology/fulltext/S0966-842X(21)00035-4 “Microbial Regulation of Host Physiology by Short-chain Fatty Acids”

PXL_20210412_104327851

Effects of another broccoli sprout compound

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

This 2020 rodent study investigated effects of broccoli sprout hydrolysis compound indole-3-carbinol:

“I3C metabolites act as ligands of the aryl hydrocarbon receptor (AhR), an important sensor for environmental polyaromatic chemicals. We investigated how dietary AhR ligand supplementation influences AhR target gene expression and intestinal microbiota composition.

Environmental signals, such as dietary, microbial, or xenobiotic factors, are sensed in intestinal tissue AhR, an important regulator of metabolism. It influences immune cell homeostasis and immune activation in the intestine.

AhR activation plays an important role in intestinal immunity, contributing to intestinal homeostasis, inflammation, and host defense:

  • AhR activation through high affinity AhR ligands has been shown to stimulate production of antimicrobial peptides.
  • AhR has been shown to be an important regulator of T cell immunity.

This indicates a major role of AhR in resolving intestinal inflammation.

High fat diet and control diet lead to reduced expression of Ahrr in intestinal immune cells.

High fat diet and control diet lead to reduced expression of Ahrr in intestinal immune cells.

Mucosal surface area of the gut represents an enormous area in direct contact with the environment. In addition to occasional pathogen encounters, the intestinal immune system is constantly exposed to antigens from diet or microbiota.

Gut-associated immune cells maintain a balance between protection against harmful infections and tolerating harmless food-derived antigens and commensals.

Our findings are in agreement with reports that dietary I3C supplementation restored AhR activation in intestinal mucosa under conditions of malnutrition and deprivation of natural AhR ligands. In humans, such malnutrition may result from a severely reduced consumption of vegetables and fruit in favor of a carbohydrate rich, high fat diet.”

https://www.mdpi.com/1422-0067/21/9/3189/htm “Dietary AhR Ligands Regulate AhRR Expression in Intestinal Immune Cells and Intestinal Microbiota Composition”

Our gut microbiota outnumber our human cells. Treat them well with broccoli sprout compounds, resistant starch, and fermentable fibers, and expect reciprocity.

Every hand’s a winner, and every hand’s a loser

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

Another great blog post Know When To Fold ‘Em by Dr. Paul Clayton:

“Newly formed proteins entering the endoplasmic reticulum must be correctly folded to achieve their final form and function. This is a complex procedure with a failure rate of over 80%.

When metabolism is sufficiently skewed, accuracy of protein folding in the endoplasmic reticulum falls below an already low baseline of 20%. Accumulation of misfolded or unfolded proteins in the endoplasmic reticulum then triggers stress.

Integrated Stress Response (ISR) is something that cells do when they are affected by major stressors:

  • ISR turns down global protein synthesis, which is designed to kill virally infected or cancerous cells. If it kills the cancer cell or virally infected cell, that is the end of it.
  • If the stressor is in the heat / hypoxia / nutrient group, however, ISR effectively puts a cell into dark mode until hard times are over. Once the stressor has passed, a cell can then start to recover and return to homeostatic health.
  • But if the stressor is sustained, a low-grade ISR continues to smolder away, causing long-term impairment locally and ultimately systemically. Accumulation of misfolded or unfolded proteins activates ISR, leading to a down-regulation of protein synthesis, and increasing protein folding and degradation of unfolded proteins.

This is analogous to inflammation. Acute inflammatory responses to a pathogen or to tissue damage are entirely adaptive, and essential. Chronic inflammation, on the other hand, causes local and eventually systemic damage if left unchecked for long enough.”

A 2020 rodent study was cited for “reversing age-related cognitive decline”:

“This suggests that the aged brain has not permanently lost cognitive capacities. Rather, cognitive resources are still there, but have been somehow blocked, trapped by a vicious cycle of cellular stress.

Our work with ISR inhibition demonstrates a way to break that cycle, and restore cognitive abilities that had become walled off over time.

stress response inhibitor effects

If these findings in mice translate into human physiology, they offer hope and a tangible strategy to sustain cognitive ability as we age.”

https://elifesciences.org/articles/62048 “Small molecule cognitive enhancer reverses age-related memory decline in mice”

I’m curious as to why sulforaphane hasn’t been mentioned even once in Dr. Paul Clayton’s blog, which started three years ago. Do thousands of sulforaphane studies performed in this century not contribute to his perspective? Polyphenols are mentioned a dozen times, yet they are 1% bioavailable compared with 80% “small molecule” sulforaphane.

Advice from the song depends on your definition of money:

“Know when to walk away
Know when to run
Never count your money
When you’re sitting at the table”

Pigs and glucosinolates

gettingwell4 4-5 stars Advanced knowledge, Epigenetics

This 2020 porcine study subject was improving healthy aspects of canola-oil-processing by-products:

“We hypothesized that inclusion of high-amylose cornstarch (HA-starch) in canola co-products-based diets for pigs can reduce hindgut pH, leading to increased degradation of glucosinolates present in hindgut of pigs into non-goitrogenic products. Most dietary myrosinases [enzymes] are inactivated by heat during cooking, pressing and toasting of canola seeds during oil extraction, implying that microorganisms that reside in the hindgut of pigs are a major source of myrosinase that degrade glucosinolates into various metabolites.

Negative effects of dietary cold-pressed canola cake (CPCC) on thyroid gland functions of nursery pigs were alleviated by dietary HA-starch. Composition of glucosinolate degradation products was dependent on parent glucosinolate type and pH conditions.

Dietary resistant starch for nursery pigs reduced cecal digesta pH from 6.07 to 5.37. Resistant starch escaped enzymatic digestion in the small intestine, and was highly fermented in hindgut of pigs.

total canola gluconisolates

Since dietary HA-starch at 40% reduced growth performance of pigs in the current study, there is a need to identify optimal dietary level of HA-starch that does not compromise growth performance of pigs fed canola co-product-based diet, or to identify alternative strategies that can be used to reduce pH in the hindgut of pigs fed canola co-product-containing diet without compromising growth performance.”

https://academic.oup.com/jas/article-abstract/98/5/skaa111/5817019 “Toxicity of canola-derived glucosinolates in pigs fed resistant starch-based diets” (not freely available)

Pig metabolism is similar to humans. Glucosinolate compound effects weren’t similar to those in sulforaphane studies because their contexts were different. Eat oats to prevent diabetes also provided evidence for what dietary resistant starch and β-glucan can achieve.

Found this study through a search term “indole-3-carbinol” restricted for 2021. It was cited in Toxicity of Canola-Derived Glucosinolate Degradation Products in Pigs—A Review coauthored by the same researchers.

Improving healthy compounds of broccoli sprouts

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

This 2020 study investigated known and experimental effects on sprouted broccoli, white mustard, red radish, and red cabbage compounds:

“We planned development of cruciferous sprouts in hydroponics elicited with LED lighting and Methyl-Jasmonate (MeJA) to bio-stimulate production of glucosinolates, comparing effects of two types of LEDs designed for indoor food production systems.

We aimed to gain knowledge on response (germination rate, biomass yield) and phytochemical composition of fresh edible sprouts of cruciferous varieties (broccoli, radish, cabbage and mustard) under these conditions for future food production recommendations:

  • Use of LED lights to grow edible cruciferous sprouts was positive in terms of biomass production and phytochemical content (glucosinolates) without any negative effects.
  • Use of MeJA was positive, confirming previous results. Intensity of response for different species is useful to focus production of sprouts for specific purposes.

3-day old sprouts were placed in a growth chamber with controlled conditions (Photoperiod 18/6 h; temperature 24/18 °C; and relative humidity 60/80%), irrigated every other day to maintain enough humidity in substrate, using 1% bleach in distilled water, and collected on day 7. Trays of germinating seeds were evenly sprayed daily with 10 mL of solution for 4 days.

4 sprouts glusosinolates affected by LED and MeJa

Total Glucosinolates (mg/100 g fresh weight) of White Mustard, Broccoli, Red Cabbage and Red Radish sprouts, under two different LED lightings, and elicited with MeJA (250 μM).

Combining MeJA spraying with different LED light treatment showed clear increases in total glucosinolate contents for all studied sprouts when sprayed for 4 days with MeJA 250 μM.”

https://www.mdpi.com/2504-3900/70/1/67/htm “The Quality and Glucosinolate Composition of Cruciferous Sprouts under Elicitor Treatments Using MeJA and LED Lights”

The research group of Our model clinical trial for Changing to a youthful phenotype with broccoli sprouts keep ramping it up. They’ve published studies of MeJA effects and LED effects on sprouts separately, but not combined like this one did.

I ordered a pound of red cabbage seeds to see how I like their 3-day-old sprouts. I started soaking mustard seeds purchased from a grocery store’s spice section last year to see if they’ll sprout.

Although effects in the above graphic are compelling, I don’t want to turn my kitchen into a laboratory with LED lights and MeJA treatments. I’ll first see if red cabbage and mustard sprouts are tolerable.

See Broccoli sprouts’ immune effects and Week 56 of Changing to a youthful phenotype with sprouts to follow on.

Several diseases, one treatment?

gettingwell4 2-3 stars Required further work, Dopamine, Epigenetics, Glutamate, Immune system, Memory, Neurochemicals, Stress ,

This 2021 review summarized three dietary supplements’ effects on psychiatric symptoms:

“Upregulation of Nrf2 has been suggested as a common therapeutic target for major neuropsychiatric disorders. In this paper, evidence is presented showing how NAC [N-acetyl-cysteine], coenzyme Q10 (CoQ), and melatonin can ameliorate many important effects of oxidative stress by upregulating Nrf2.

Given its key role in governing cellular antioxidant response, upregulation of Nrf2 has been suggested as a common therapeutic target in neuropsychiatric illnesses such as major depressive disorder, bipolar disorder, and schizophrenia. These are associated with chronic oxidative and nitrosative stress, characterised by elevated levels of reactive oxygen species, nitric oxide, and peroxynitrite.

CoQ:

  • Acts as a superoxide scavenger in neuroglial mitochondria;
  • Instigates mitohormesis;
  • Ameliorates lipid peroxidation in the inner mitochondrial membrane;
  • Activates uncoupling proteins;
  • Promotes mitochondrial biogenesis; and
  • Has positive effects on the plasma membrane redox system.

Melatonin:

  • Scavenges mitochondrial free radicals;
  • Inhibits mitochondrial nitric oxidesynthase;
  • Restores mitochondrial calcium homeostasis;
  • Deacetylates and activates mitochondrial SIRT3;
  • Ameliorates increased permeability of the blood-brain barrier and intestine; and
  • Counters neuroinflammation and glutamate excitotoxicity.”

https://www.researchgate.net/publication/348309816_Increasing_Nrf2_Activity_as_a_Treatment_Approach_in_Neuropsychiatry “Increasing Nrf2 Activity as a Treatment Approach in Neuropsychiatry” (registration required)

These reviewers explored three selected supplements, citing 380 references. They overlooked something, though. There was only one mention of sulforaphane in their paper, yet four references’ titles included sulforaphane?

I take two of the three exogenous supplements discussed. The one I stopped taking over a year ago – NAC – was thoroughly discussed, but not in contexts directly related to the Nrf2 transcription factor. Why?

Switch on your Nrf2 signaling pathway pointed out:

“We use NAC in the lab all the time because it stops an Nrf2 activation. So that weak pro-oxidant signal that activates Nrf2, you switch it off by giving a dose of NAC. It’s a potent antioxidant in that right, but it’s blocking signalling. And that’s what I don’t like about its broad use.”

The current review noted that Nrf2 is activated by oxidative stress. NAC is a precursor to glutathione – our main endogenous antioxidant – and neither one activates Nrf2 pathways.

What does? Sulforaphane.

PXL_20210412_104353167

Repositioning DNA methylation

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

This 2021 human study found:

“We report on a randomized controlled clinical trial conducted among 43 healthy adult males between the ages of 50-72. The 8-week treatment program included diet, sleep, exercise and relaxation guidance, and supplemental probiotics and phytonutrients.

This is the first randomized controlled study to suggest that specific diet and lifestyle interventions may reverse Horvath DNAmAge (2013) epigenetic aging in healthy adult males. Larger-scale and longer duration clinical trials are needed to confirm these findings, as well as investigation in other human populations.

aging-v13iundefined-202913-figure-f3

In both treatment and control groups, there was no net increase or decrease in methylation of 353 sites that compose the Horvath clock. This finding suggests that intervention did not lead to an overall increase in methylation of Horvath clock sites, but rather it prompted a repositioning of clock CpG methylation patterns consistent with a younger biological age.

One significant limitation of this pilot trial is limited statistical power due to relatively small sample size. It is not yet fully established whether interventions that slow any methylation clocks necessarily curtail risks of age-related disease.”

https://www.aging-us.com/article/202913/text “Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial”

Baffled as to why these researchers relied on 2013 research rather than at least Dr. Horvath’s improved 2018 skin and blood clock, a review of which noted:

“Although the skin-blood clock was derived from significantly less samples (~900) than Horvath’s clock (~8000 samples), it was found to more accurately predict chronological age, not only across fibroblasts and skin, but also across blood, buccal and saliva tissue. A potential factor driving this improved accuracy in blood could be related to the approximate 18-fold increase in genomic coverage afforded by using Illumina 450k/850k beadarrays.”

Which would you prefer? A 2013 flip phone, or a 2018 smartphone?

A bat epigenetic clock

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

This 2021 study subject was bats:

“Exceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity.

Hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that:

  • Age-related methylation change is influenced by developmental processes, while
  • Longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that
  • Bat longevity results from augmented immune response and cancer suppression.

Molossus molossus [a short-lived species] age genes are not enriched for immunity genes or genes that frequently mutated in cancer. However, M. molossus longevity genes exhibit significant overlap with genes involved in immunity and genes frequently mutated in human tumors.

Similar overlap patterns among immunity, longevity, and tumor-mutated genes also exist for long-lived bats.

Two species’ genetic adaptations for tumor suppression have been described to help explain their extreme longevity. Bats also have genetic mechanisms that enable strong antiviral immune responses without inducing damaging inflammatory reactions that may enable them to tolerate high levels of viral exposure.

Our results are consistent with an epigenetic clock theory of aging that connects beneficial developmental and cell maintenance processes to detrimental processes causing tissue dysfunction.”

https://www.nature.com/articles/s41467-021-21900-2 “DNA methylation predicts age and provides insight into exceptional longevity of bats”

The founder of the epigenetic clock has been busy, coauthoring more published studies than there have been weeks in this year! I’ve read five other 2021 studies he’s coauthored on dogs, horses, mammals (2), and humans in DNA methylation biomarker for cumulative lead exposure is associated with Parkinson’s disease. This one stood out for its “longevity results from augmented immune response and cancer suppression” findings.

If we’re interested in longevity, this clarity can direct efforts to both improve our immune systems and avoid problems like cancer. Symptoms may be subclinical, but that doesn’t provide adequate rationale to not address causes.

Peer review comments and responses were informative:

Reviewer #1 – “Developing an aging clock that works for a diverse set of bat species is a spectacular achievement.”

Reviewer #2 – “This is a tour de force study.”

Replies to Reviewer #3:

“Difference in recorded lifespans between three long-lived species and two short-lived species that we used to identify longevity DMPs [differentially methylated positions] is 20 years or more, even though they have similar body sizes (20-40 g). The three long-lived species [maximum ages 29.9, 30.5, and 37.1 years] also represent three different phylogenetic lineages.

CpG sites that undergo hypomethylation with age do so largely at random. In contrast, sites that undergo hypermethylation with age are highly nonrandom, and as has been noted before, are near genes associated with development. So yes, we believe there are predictable methylation changes with age.”

Train your gut microbiota with taurine

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

This 2021 rodent study found:

“We show that gut microbiota from previously infected hosts display enhanced resistance to infection. This long-term functional remodeling is associated with altered bile acid metabolism leading to expansion of taxa that utilize taurine.

Supplying exogenous taurine alone is sufficient to induce this alteration in microbiota function and enhance resistance. Taurine potentiates microbiota production of sulfide, an inhibitor of cellular respiration, which is key to host invasion by numerous pathogens.

fx1_lrg

This work reveals a process by which the host, triggered by infection, can deploy taurine as a nutrient to nourish and train microbiota, promoting its resistance to subsequent infection.”

https://www.cell.com/cell/fulltext/S0092-8674(20)31681-0 “Infection trains the host for microbiota-enhanced resistance to pathogens” (not freely available)

News coverage added:

“The studied infections induced host taurine production and expansion of taurine utilizers. Taurine was the trigger for activity of a class of bacteria that fight these infections.

The group’s data suggest that low levels of taurine allow pathogens to colonize the gut, but high levels produce enough hydrogen sulfide to prevent colonization. Taurine given to mice in drinking water prepared microbiota to prevent infection. However, when mice drank water containing bismuth subsalicylate, a common over-the-counter drug used to treat diarrhea and upset stomach, infection protection waned because bismuth inhibits hydrogen sulfide production.”

Can’t calculate a human equivalent dose without access to this study. I take 1 gram of taurine twice a day.

Per Treating psychopathological symptoms will somehow resolve causes? I resumed taurine supplementation last year after taking a year’s break. From that paper’s taurine section:

“Most studies that reported enhanced GSH [glutathione] in the brain following taurine treatment were performed under a chronic regimen and used in age-related disease models.

Such positive effects of taurine on GSH levels may be explained by the fact that cysteine is the essential precursor to both metabolites, whereby taurine supplementation may drive metabolism of cysteine towards GSH synthesis.”

If that paper’s hypothesis is correct, and the current study’s evidence is replicable, taurine supplementation is a win-win for both our brain and gut microbiota.

Sunrise minus 5 minutes

Let β-glucan train your brain

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

This 2021 rodent study investigated yeast cell wall β-glucan’s effects on the brain’s immune system:

“Innate immune memory can manifest in two different ways, [1] immune training and [2] immune tolerance, which means [1] an enhanced or [2] suppressed immune response towards a secondary challenge. Lipopolysaccharide (LPS) and β-glucan (BG) are two commonly used ligands to induce immune training and tolerance.

Microglia, the innate immune cells of the central nervous system, can adopt diverse phenotypes and functions in health and disease. In our previous study, we have shown that LPS preconditioning induces immune tolerance in microglia.

Compared to LPS, relatively little is known about effects of BG on microglia. In this study, we report for the first time that systemic administration of BG activates microglia in vivo, and that BG preconditioning induces immune training in microglia.

dectin-1

Our results show that BG activated microglia without inducing significant cytokine expression.

BG- and LPS-preconditioning both induced immune training in microglia two days after the first challenge. However, with an interval of 7 days between the first and second challenge, LPS-preconditioning induced immune tolerance in microglia where BG-induced immune training was no longer detected.”

https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-021-02103-4 “Systemic administration of β-glucan induces immune training in microglia”

One solution to “BG-induced immune training was no longer detected” after 7 days is to take β-glucan every day. I haven’t seen studies that found β-glucan induced immune tolerance, i.e. “suppressed immune response towards a secondary challenge.”

I take allergy medicine twice a day. Switched over to a different β-glucan vendor and dose per Year One of Changing to a youthful phenotype with broccoli sprouts.

I take 1 gram of Glucan 300 capsules without eating anything an hour before or an hour afterwards. I’ve only been doing it for a week, though, and haven’t been able to separate out β-glucan effects on seasonal allergies. I’ll try stopping allergy medicine when pollen stops coating my car.

PXL_20210405_103925702
Swarming a spring sea trout run. Ospreys outcompeted gulls for breakfast.

Eat broccoli sprouts for your heart

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

This 2021 rodent study investigated mechanisms of sulforaphane’s persistent cardiac protection:

“Sulforaphane (SFN) reduced Ang II‐induced CpG hypermethylation and promoted Ac‐H3 [histone H3 acetylation] accumulation in the Nrf2 promoter region, accompanied by inhibition of global DNMT [DNA methyltransferase] and HDAC [histone deacetylase] activity, and a decreased protein expression of key DNMT and HDAC enzymes. Overall, DNA methylation and histone deacetylation are considered to inhibit gene transcription with a synergistic effect.

jcmm16504-fig-0006-m

SFN reduces CpG methylation and promotes enrichment of Ac‐H3 in Nrf2 promoter by inhibiting DNMTs and HDACs. This partially contributes to long‐acting activation of cardiac Nrf2, thereby preventing Ang II‐induced cardiomyopathy.”

https://onlinelibrary.wiley.com/doi/10.1111/jcmm.16504 “Sulforaphane prevents angiotensin II‐induced cardiomyopathy by activation of Nrf2 through epigenetic modification”

This study used the same dose of sulforaphane as Broccoli sprouts activate the AMPK pathway, but stopped at six months (equivalent to a 34-year-old human) rather than continuing to eight months (a 42-year-old human):

“0.5 mg/kg SFN in mice is converted to a human dose of 0.0405 mg/kg. In some clinical studies, the dose of SFN used to treat chronic diseases is usually higher. The dose of SFN used in this study is relatively low and safe.”

Findings highlighted:

  1. A disease condition existed in young adults that wasn’t severe enough for them to experience overt symptoms; and
  2. A disease condition could be reversed or prevented when its causes were addressed before it became a problem.

Studies such as one mentioned in Part 2 of Eat broccoli sprouts for your eyes showed that if one waited until a disease condition became a problem, capabilities to adequately address causes and prevent it may be lost. Do you want to be limited to addressing a disease’s symptoms once it gets bad enough to be noticeable?

Both studies found positive effects of sulforaphane in preventing cardiomyopathy. The 2020 study demonstrated in myocardial cells that sulforaphane’s activation of the AMPK pathway – which is upstream of the Nrf2 pathway – activated Nrf2:

“NRF2-mediated antioxidative effects can be activated via AMPK/AKT/GSK3β pathway, developing another pathway to confront cardiac oxidative damage.”

The current study similarly stated:

“Nrf2 can also be regulated independently of Keap1. Evidence indicates that SFN may indirectly activate Nrf2 by affecting activity of several upstream kinases.”

Both studies’ “human dose of 0.0405 mg/kg” were a minuscule 2.8 mg (.0405 mg/kg x 70 kg) human dose compared with my estimated daily 52 mg of sulforaphane from eating 65.5 grams of microwaved 3-day-old broccoli sprouts twice daily. Yet that small amount of sulforaphane was able to prevent a daily dose of angiotensin II from causing conditions that would lead to heart disease.

I linked this study yesterday in Reversing osteoporosis with Nrf2 as an example of similarities with exercise and eating broccoli sprouts. While activating my Nrf2 pathways this morning by walking four miles at sunrise, I came across a heron who tolerated me getting close to them:

PXL_20210407_110723070

It ate breakfast off a branch, and pecked bugs from the water if they hopped off.

Reversing osteoporosis with Nrf2

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

This 2021 rodent study made old females out of young females by removing their ovaries, which induced osteoporosis. They then demethylated the Nrf2 gene promoter with exercise, increasing its expression, which reversed osteoporosis:

“Nrf2 repression due to aberrant Dnmt elevation and subsequent Nrf2 promoter hypermethylation is an important epigenetic feature of osteoporosis (OP) pathogenesis.

Nrf2 promoter demethylation

Ovariectomized mice display increased femoral Dnmt1/3a/3b (Dnmts), Nrf2 promoter hypermethylation, and Nrf2 suppression, which promote oxidative stress (OS), osteoclastogenesis (OCG) and OP (dashed line).

Running exercise (RE, solid line) normalizes Dnmt aberrations, resulting in Nrf2 promoter demethylation, Nrf2 recovery and reduced femoral osteoporotic pathologies.

Nrf2 repression due to aberrant Dnmt elevations and associated promoter hypermethylation contributes significantly to epigenetic development of OP. RE effectively corrects epigenetic abnormalities and pathogenesis of OP.”

https://www.nature.com/articles/s41413-020-00128-8 “Nrf2 epigenetic derepression induced by running exercise protects against osteoporosis”

Running an hour every day has effects on Nrf2 gene promoter expression similar to eating broccoli sprouts. A 2021 study Sulforaphane prevents angiotensin II‐induced cardiomyopathy by activation of Nrf2 through epigenetic modification found:

“SFN reduced Ang II‐induced CpG hypermethylation and promoted Ac‐H3 accumulation in the Nrf2 promoter region, accompanied by inhibition of global DNMT and HDAC activity, and a decreased protein expression of key DNMT and HDAC enzymes.”

A 2019 study Sulforaphane‑induced epigenetic regulation of Nrf2 expression by DNA methyltransferase in human Caco‑2 cells found:

“DNMT1 protein expression was inhibited by sulforaphane. Nrf2 promoter methylation decreased significantly in the sulforaphane group.

Sulforaphane may promote demethylation of the Nrf2 promoter region to increase activation of Nrf2.”

Per Week 6, my running days are over, though not walking, climbing, etc. Nrf2 activation with broccoli sprouts began after two weeks of self-quarantine more than a year ago.

Improving one’s own health provides sufficient rationale to act.