Month: July 2020

Sulforaphane and RNAs

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

This 2020 Texas review subject was long non-coding RNAs:

“We review the emerging significance of long non-coding RNAs (lncRNA) as downstream targets and upstream regulators of the Nrf2 signaling pathway, a critical mediator of diverse cellular processes linked to increased cell survival.

It is believed that more than 3% of human genes are regulated by the Nrf2/Keap1 pathway. In addition to the classical cytoprotective and oxidative stress response genes transactivated by Nrf2, emerging evidence suggests a role for non-coding transcript regulation at the level of noncoding RNAs, [which] far outnumber protein-coding genes in the human genome.

One important distinction between miRNAs and lncRNAs is that the latter are often species-specific, meaning that a human lncRNA typically cannot be studied in the mouse or rat, and vice versa.

Sulforaphane (SFN) acts via multiple mechanisms to modulate gene expression, including the induction of Nrf2-dependent signaling. In addition to the established canonical targets of Nrf2, such as NQO1 and HMOX1, SFN altered the expression of multiple lncRNAs.

Given that SFN induces NMRAL2P [a lncRNA pseudogene] and several other lncRNAs in colon cancer cells, further studies are warranted on their respective roles as upstream regulators and/or downstream targets of Nrf2 signaling.

Pharmacological modulation of Nrf2 is considered a viable strategy against chronic conditions that are accompanied by oxidative stress and inflammation:

  • DMF [dimethyl fumurate] is the most successful Nrf2 activator, FDA-approved in 2013 for the treatment of relapsing remitting multiple sclerosis. However, DMF causes leukopenia and other side-effects.
  • Bardoxolone cleared Phase II clinical trials for the treatment of advanced chronic kidney disease and type 2 diabetes mellitus, but was halted in Phase III trials due to cardiovascular concerns.
  • SFN is relatively unstable at room temperature.

We used reported bioinformatics approaches to search for putative ARE [antioxidant response element] sequences among the entire set of 16,000+ annotated human lncRNAs. 13,285 promoter regions contained one or more potential binding sites for Nrf2.”

https://www.sciencedirect.com/science/article/pii/S0304383520303670 “Emerging crosstalk between long non-coding RNAs and Nrf2 signaling”

This study hyped lncRNAs in that only 7 have been validated as Nrf2 targets, and 8 validated as Nrf2 regulators. For regulators, “protein and/or miRNA interacting partners are yet to be fully corroborated” as well.

Also, there’s no need for a “SFN is relatively unstable at room temperature” problem. Just create sulforaphane right before consuming it.

Twice a day I microwave an average 65.5 grams of 3-day-old broccoli sprouts immersed in 100 ml water with a 1000W microwave on full power for 35 seconds to ≤ 60°C. After microwaving I transfer broccoli sprouts to a strainer, and wait five minutes to allow further myrosinase hydrolization of glucoraphanin and other glucosinolates into sulforaphane and other healthy compounds.

Reprogram inflammation with β-glucan

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

This 2020 French human cell study found:

“Exposure of mononuclear phagocytes to β-glucan contributes to the induction of innate immune memory, which is associated with long-term epigenetic, metabolic, and functional reprogramming. We investigated how preincubation of human monocytes with particulate β-glucan affects the biological response of macrophages following NLRP3 inflammasome activation.

Upon infection or cellular damage, NLRP3 assembles into a multiprotein inflammasome complex leading to the release of IL-1β. However, NLRP3 inflammasome activity can also be detrimental to the host, and its aberrant chronic activation is associated with severe pathologies.

β-Glucan is a safe molecule present in food products and already widely used in food supplementation. Although β-glucan–induced innate memory is associated with a nonspecific protective effect against infections, the role of this functional reprogramming in autoinflammatory disorders is unknown.

Because of the administration frequency and conservation needs, IL-1β–targeted therapy is invasive, complex, and also costly. In addition, IL-1β, an acute-phase protein, is crucial for effective immune responses to infection, and inhibitors targeting IL-1β may lead to unintended immunosuppressive effects in addition to preventing NLRP3 inflammasome activity in itself.

Targeting the origin of the disease, i.e., NLRP3, would represent the best therapeutic strategy. Most of these candidate drugs directly interact with NLRP3, but none seems to regulate the early activation events upstream of NLRP3 inflammasome assembly.

β-Glucan acted upstream of the NLRP3 inflammasome. β-glucan–induced innate immune memory represses IL-1β–mediated inflammation and support its potential clinical use in NLRP3-driven diseases.”

https://www.jci.org/articles/view/134778 “β-Glucan–induced reprogramming of human macrophages inhibits NLRP3 inflammasome activation in cryopyrinopathies”

This study came closer to addressing causes than others with:

“Targeting the origin of the disease would represent the best therapeutic strategy.”

It’s apparently too recent with a July 27th published date to make it onto https://www.betaglucan.org/i-p/, but earlier β-glucan inflammation studies may be found there.

Topical sulforaphane protects skin

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

This 2020 Rutgers rodent study explored topical application of sulforaphane to prevent UVB-induced skin carcinogenesis:

“We investigated the transcriptomic and DNA methylomic changes during tumor initiation, promotion, and progression and its impact and reversal by sulforaphane (SFN). The production of ROS and inflammation are closely linked to UVB-induced carcinogenesis. SFN protects skin cells from UVB-induced damage mainly through promoting anti-inflammatory, antioxidative and anticancer pathways.

We observed the changes after 2, 15 and 25 weeks of UVB exposure, which would represent the three different stages of skin cancer development. After 2 weeks of UVB exposure, we did not observe any obvious tumors in the UVB group. But after 15 weeks of UVB exposure, some obvious tumors were observed in the skin.

After 15 weeks of UVB treatment in epidermal tissue, the difference between the UVB group and the control group was significantly more than that between the SFN group versus the UVB group. SFN appears to have better cancer-protective effects in earlier time points (weeks 14 and 20) than later time point (week 24). At weeks 20, SFN had significantly fewer tumors with decreased total tumor volume and tumor number.

SFN plays a highly regulatory role in various signaling pathways during UVB irradiation. SFN impacts UVB-induced alterations of DNA methylation profiles, and importantly, SFN treatment attenuates some of these DNA methylation changes. We found a subset of genes associated with SFN treatment, and the relevant changes in gene expression may be driven by promoter CpG methylation status.”

https://cancerpreventionresearch.aacrjournals.org/content/13/6/551 “Epigenome, Transcriptome, and Protection by Sulforaphane at Different Stages of UVB-Induced Skin Carcinogenesis” (not freely available)

We’re getting closer to using epigenetic clocks in sulforaphane studies. This study ignored the 2018 A multi-tissue full lifespan epigenetic clock for mice in favor of their homegrown DNA methylation measurements.

A search of ClinicalTrials.gov didn’t turn up directly relevant human studies.

Supporting individuals

gettingwell4 Just me

This past Saturday evening into night I walked five miles over three hours in Manchester, New Hampshire, with two individuals. Several items of interest, incidental to our enjoyable experiences:

  • My first impression was that it could have been this time last year. People who had spent a long winter and spring indoors were happy to be outdoors.
  • There were small differences from 2019 in that outdoor and indoor tables were widely spaced, and a few customers wore masks. We ate a meal indoors that included good paella, ceviche, and calamari.
  • I didn’t see instances of violence or property crimes.
  • I observed social deviancy in ~1% of the people. A crazy person talked to herself while walking down the sidewalk carrying a plastic garbage bag full of who-knows-what – worldly belongings? One homeless person slept off a binge, another engaged in a binge with a bottle in front of him, while a third walked glassy-eyed, accompanied by counsel.

I didn’t see any people my chronological age outdoors. Okay, it was Saturday night.

I encourage every individual to take responsibility for every aspect of each of our own one precious life.

I strongly object to destroying society among individuals, especially young people’s social and economic lives. Current cover stories promise to destroy a person’s social presence, reputation, residence, economic development – whatever it takes – to conform them to the desired “norm.”

Should we destroy society to ostensibly (“outwardly appearing as such; professed; pretended“) protect people who don’t take responsibility for themselves?

  • For our own non-communicable diseases like Type 2 diabetes, obesity, etc., that make us susceptible to other diseases?
  • For our own neglected health issues that we look to others to resolve instead of looking to ourselves?

Will Part II be governments granting themselves even more powers with a cover story that they will restore the order they destroyed?

The individuals I walked with support open-carry firearms. Instances of property crimes and violence I saw: 0 among ~400 people outdoors. I saw three that supported open carry:

  1. A pub owner or manager;
  2. A person on Manchester’s main street; and
  3. A person shouting from their car.

Instances of property crimes and violence in US cities on Saturday night who prohibit open carry? Look up:

  • Seattle (at least 59 people injured by mob violence);
  • Portland (another day after day, week after week, month after month of unarrested mob property crimes and violence);
  • Chicago (another day that added to the 2,200+ people shot by gangs during 2020).

What went on in your city this past Saturday night?

Politically correct about erucic acid and broccoli seeds

gettingwell4 < 0 Detracted from science

To follow up Caution on broccoli seed erucic acid content? this 2020 German review sympathetically analyzed government overreach on erucic acid contents in several foods:

“We measured exemplarily samples of rapeseed, mustard, further Brassicaceae and used the data to discuss possible consequences for consumers, producers and the food sector. This data was supplemented with possible analytical problems.

The new and lower erucic acid level in the EU is anticipated but will increase the need of an efficient control system by producers and food processors in order to avoid violations of erucic acid limit values and sale bans. The new proposed legislation will likely prompt some producers to reformulate their recipes, which can be achieved by lowering the fat content or by moving to mustard seeds with lower erucic acid content.

The amount of erucic acid in fish should not be neglected.”

https://www.sciencedirect.com/science/article/pii/S235236462030002X “Erucic acid in Brassicaceae and salmon – An evaluation of the new proposed limits of erucic acid in food” (not freely available)

The paper didn’t measure erucic acid percentages of total fatty acids in broccoli seeds. Also noticeably absent were analyses of animal studies performed a long time ago that formed the bases of current government actions. See Beneficial dietary erucic acid? for important evidence available at the time that was intentionally overlooked and misinterpreted:

“Erucic acid is found to cause cardiac lipidosis in young animals, yet direct evidence of cardiac injury does not exist for young humans. Concerns about erucic acid safety and cardiotoxicity have been published in the press which are based on scientific reports in the 1970s that erucic acid disrupted oxidative phosphorylation and lead to accumulation of lipids in rat cardiac tissue.

Spanish toxic oil syndrome was a major concern, leading to questions about erucic acid cardiotoxicity. Yet it was found that not rapeseed oil per se, rather its carcinogen anilin-dye refined derivative caused cardiotoxicity.

Later, it was understood that reduced ATP production with erucic acid treatment was due to unapt isolation of rat cardiac mitochondria and lipid accumulation that was unique to rats that inherently harbour a low β-oxidative peroxisomal activity and tissue-specific metabolism of erucic acid. Similar structural or metabolic perturbations and tissue injuries were not encountered in monkeys, humans, and pigs.”

Nothing to see here, move along. Much more effort was put into creating new health hazards for consumers, as if we should now be required to worry about eating salmon.

The 2017 position paper establishing erucic acid limits was excessively cited twelve times, such as for:

“Likewise, broccoli seeds were high in erucic acid but this fatty acid was not detected in edible parts of the vegetable. Hence, intake of erucic acid via these vegetables seems to be irrelevant.”

I mentioned problems in the poorly-evidenced 2002 study cited by this position paper. That researcher couldn’t be bothered to use just one broccoli cultivar for only three measurements, or disclose broccoli sprout age. But apparently it’s a fait accompli, elevated to an indisputable fact.

Despite many technical details, the current paper was politics. It detracted from science, with a cover story “in favor of consumer protection.” Poorly-evidenced assertions are not science.

These researchers descended further into advocacy with “analysis” beginning with:

“Imagine (cruciferous) vegetables having an erucic acid content of 50% in the lipids.”

They did cause me to “imagine” eating hot dogs with mustard. But maybe that’s because baseball season is finally starting?

These vendors of broccoli seed powder don’t seem concerned about disclosing erucic acid content. What do you think?

🙂

Caution on broccoli seed erucic acid content?

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

1. While looking through PubMed “broccoli skin” search results, I read a 2018 study Comparative Study of Predominant Phytochemical Compounds and Proapoptotic Potential of Broccoli Sprouts and Florets that cautioned about erucic acid content in broccoli seeds:

“Our results revealed significantly higher total UFAs [unsaturated fatty acids] content in the sprouts in comparison to the florets, with very low amounts of harmful erucic [27] acid in sprouts (0.5%) and florets (2%), in comparison to the broccoli seeds (38% – data not shown).”

But its cited reference [27] Various concentrations of erucic acid in mustard oil and mustard said nothing about broccoli seeds.

Values were on a dry weight basis. Broccoli sprout age was four days.

2. Another search found this 2017 Erucic acid in feed and food position paper which stated:

“When in this Scientific Opinion the erucic acid content is reported as a percentage, this value refers to the percentage erucic acid in the total fatty acids on a weight basis.

A tolerable daily intake of 7 mg/kg body weight per day for erucic acid was established.”

See Beneficial dietary erucic acid? for important evidence available at the time that was intentionally overlooked and misinterpreted:

“Erucic acid is found to cause cardiac lipidosis in young animals, yet direct evidence of cardiac injury does not exist for young humans. Concerns about erucic acid safety and cardiotoxicity have been published in the press which are based on scientific reports in the 1970s that erucic acid disrupted oxidative phosphorylation and lead to accumulation of lipids in rat cardiac tissue.

Spanish toxic oil syndrome was a major concern, leading to questions about erucic acid cardiotoxicity. Yet it was found that not rapeseed oil per se, rather its carcinogen anilin-dye refined derivative caused cardiotoxicity.

Later, it was understood that reduced ATP production with erucic acid treatment was due to unapt isolation of rat cardiac mitochondria and lipid accumulation that was unique to rats that inherently harbour a low β-oxidative peroxisomal activity and tissue-specific metabolism of erucic acid. Similar structural or metabolic perturbations and tissue injuries were not encountered in monkeys, humans, and pigs.”

3. It referenced a 2002 Determination and Health Implication of the Erucic Acid Content of Broccoli Florets, Sprouts, and Seeds which stated:

“The erucic acid content of broccoli florets, sprouts, and seeds was found to be about 0.8, 320, and 12100 mg/100 g, respectively.”

Respective erucic acid percentages of total lipids on a fresh weight basis were provided as 0.4%, 1.1%, and 26.9%.

Florets, sprouts, and seeds had no relationships among them as they were different broccoli cultivars. Broccoli sprouts’ age wasn’t disclosed.

4. The 2002 study was updated in a 2004 Glucoraphanin and 4-Hydroxyglucobrassicin Contents in Seeds of 59 Cultivars of Broccoli, Raab, Kohlrabi, Radish, Cauliflower, Brussels Sprouts, Kale, and Cabbage which stated:

“All seed accessions contained substantial amounts of hexane-extractable lipids ranging from 21.8 to 42.0% (mean of 32.8%; 21.8-37.0 and 30.9% range and mean, respectively, for broccoli cultivars only), which were composed of 27.0-56.7% (mean of 46.7%;39.4-56.7 and 50.2% range and mean, respectively, for broccoli cultivars only) erucic acid.”

Seeds of the 2002 broccoli sprouts commercial product were measured at 31.4% lipids, with erucic acid content 51.6% of total lipids.

5. The 2018 study cited a 2013 Biochemical composition of broccoli seeds and sprouts at different stages of seedling development whose broccoli seed and sprout composition dry weights are in the below graphic:

  • Broccoli seed lipid percentage of total carbohydrates plus crude fiber would be 9.36 g / (58.89 g + 15.47 g) = 12.6%.
  • 3-day-old broccoli sprouts lipid percentage of total carbohydrates plus crude fiber would be 8.67 g / (54.4 g + 8.97 g) = 13.7%.
  • No erucic acid contents were disclosed.

These four studies all required further work:

  • 2002 couldn’t be bothered to use just one broccoli cultivar for its three measurements, or disclose broccoli sprout age.
  • 2004 couldn’t resolve many of their findings with other studies.
  • 2013 used weights to equate measurements, instead of relating germination stages back to a beginning number of seeds and their measurements.
  • 2018 provided a bogus reference and an unsupported “broccoli seeds (38% – data not shown).” It claimed similarity with 2013, but a statistics package would say otherwise. It also didn’t comply with disclosing fatty acids weight as a percentage of broccoli sprouts weight.

Home sprouting has to deal with:

  • unknown cultivar,
  • unknown glucoraphanin and other glucosinolates contents,
  • unknown sulforaphane and other healthy compounds, and now
  • unknown erucic acid content.

Let’s reverse Microwave broccoli seeds to create sulforaphane calculations with 3-day-old broccoli sprouts have the optimal yields information to estimate an erucic acid content in one tablespoon of broccoli seeds. Measurements from Week 18 and Week 19 of Changing to a youthful phenotype with broccoli sprouts.

  • Broccoli seed weight of one tablespoon 10.7 g.
  • Lipids weight (10.7 g x 12.6% [2013 study]) = 1.35 g.
  • Erucic acid weight in one tablespoon of broccoli seeds (1.35 g x 26.9% [2002 study]) = 0.36 g.

This 0.36 g erucic acid content would be lower than 2017 guidelines for my 70 kg weight (7 mg x 70) = 0.49 g.

Let’s reverse Estimating daily consumption of broccoli sprout compounds techniques to estimate an erucic acid content in my daily consumption of 3-day-old broccoli sprouts grown from two tablespoons of seeds:

  • 131 g 3-day-old broccoli sprouts.
  • Maximum lipids weight (131 g x 13.7% [2013 study]) = 17.9 g.
  • Maximum erucic acid weight in 3-day-old broccoli sprouts (17.9 g x 1.1% [2002 study]) = 0.20 g.

Plug in your own numbers, but it looks like caution isn’t warranted for broccoli seed consumption. Consequences of a possible erucic acid content may be less than broccoli seeds’ healthy aspects.

One mitigation may be to start germination. Pick a point between broccoli seeds’ % of total fatty acids and ending 0.5% of 4-day-old sprouts [2018 study].

Not concerned with a daily estimate < .49 g erucic acid for broccoli seeds and sprouts. Back to a PubMed “broccoli skin” search.

See Politically correct about erucic acid and broccoli seeds for a follow up.

Eat sauerkraut today!

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

This 2017 Spanish article reviewed health benefits of sauerkraut:

“During cabbage shredding and fermentation, a disruption of cabbage cells occurs, and GLS [glucosinolates] are hydrolyzed by myrosinase enzyme to a variety of GLS breakdown products. In particular, glucobrassicin is hydrolyzed into indol-3-carbinol (I3C) by myrosinase.

As the pH decreases during cabbage fermentation, I3C reacts nonenzymatically with ascorbic acid to yield ascorbigen (ABG). Studies have shown that ABG is the main GLS breakdown compound in sauerkraut, and it is present at levels between 3 and 18 μmol/100 g fw.

The antioxidant activity observed for sauerkraut in all studies was higher than that observed in raw cabbage.

It has been reported that doses between 53 and 150 μmol of ITCs [isothiocyanates] are enough to display anticarcinogenic effects. Taking into account that the content of ITCs in sauerkraut is in the range 22 μmol/100 g fw, it could be assumed that a weekly consumption of 200–250 g of sauerkraut would provide effective ITC doses to exert cancer chemopreventive effects.

Many studies reported that LAB [lactic acid bacteria] isolated from sauerkraut are potential probiotics.”

https://www.sciencedirect.com/science/article/pii/B9780128023099000248 “Sauerkraut: Production, Composition, and Health Benefits” (not freely available)

This introductory article presented interesting facts, but oversold sauerkraut. Dose and other conditional dependencies in order to achieve health and disease prevention benefits seemed to be beyond its scope.

A more considered view was offered in Fermented Food and Non-Communicable Chronic Diseases which referenced this article:

“Clinical data about the effects of sauerkraut on the human organism, health and disease are scarce. There is knowledge concerning particular compounds in sauerkraut and their impacts on diseases; however, a literature search revealed mostly cell line or rat experiments with very limited conclusions for humans.”

Earlier this month I started eating refrigerated sauerkraut twice a day with microwaved broccoli sprouts. I mix in three heaping teaspoons each time, and finish a 50 oz (1418 g) container in a week.

The mixture tastes better than just microwaved broccoli sprouts. It requires more chewing, which assists myrosinase hydrolization of broccoli sprout glucosinolates into sulforaphane and other healthy compounds.

Although sauerkraut isn’t a primary source, there may be beneficial amounts of probiotics etc. that increase what I get with broccoli sprouts and supplements.

I also started making my own sauerkraut using the commercial product’s juice as a starter. I add garlic but not salt. No results yet.

The amount of money being created has almost gone vertical

gettingwell4 Just me

From Saved by the printing press – for now:

“In the three-month period ended 6/11/2020, the Fed balance sheet expanded by 66% as it grew from $4.2 Trillion to $7.2 Trillion. Most of that growth has been the purchase of US Treasuries as the Fed has had to monetize deficits.

If you find yourself wondering how the government can issue this much debt and still maintain ‘full faith and credit’ in the currency then you are not alone.

Who is financing these deficits? The Fed.

The amount of money being created has almost gone vertical.”

Any doubt about where we’re headed?

“A display of extremely high food prices during hyperinflation” from Rare Historical Photos.

From Currency devaluation, the most destructive policy of all, the next trick to be pulled out of a hat:

“Devaluation policy sends false price signals into the economy, which leads to more investing mistakes than would otherwise happen.

Keynes wasn’t right about much, but early in his career he was absolutely right about currency devaluation. It is a process that engages all the hidden forces of economic law on the side of destruction, and it does so in a manner that not one man in a million will be able to diagnose.”

Transgenerational epigenetic inheritance of epimutations

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

My 600th curation is a 2020 rodent study from Dr. Michael Skinner’s labs at Washington State University:

“Numerous environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of disease and phenotypic variation. Alterations in the germline epigenome are necessary to transmit transgenerational phenotypes.

In previous studies, the pesticide DDT and the agricultural fungicide vinclozolin were shown to promote the transgenerational inheritance of sperm differential DNA methylation regions, non-coding RNAs and histone retention, which are termed epimutations. The current study was designed to investigate the developmental origins of the transgenerational differential histone retention sites (called DHRs) during gametogenesis of the sperm.

In addition to alterations in sperm DNA methylation and ncRNA expression previously identified, the induction of DHRs in the later stages of spermatogenesis also occurs. This novel component of epigenetic programming during spermatogenesis can be environmentally altered and transmitted to subsequent generations.

While the DHR may be consistent and present between the stages of development, the histone modifications may be altered. Several of the core histone retention sites absent in the DHRs had altered histone methylation. This adds a level of complexity to the potential role of histone retention in that it may be not only the retention, but also the alterations in histone epigenetic modifications.

The DHRs had positional associations with genes and the major functional categories were signaling, metabolism and transcription.

In the event the embryo stem cell population has a modified epigenetics and corresponding transcriptome, then all somatic cells derived from the stem cell population will have an altered cascade of epigenetic and gene expression programming to result in adult differentiated cells with altered epigenetics and transcriptomes. Previous observations have demonstrated in older adult human males alterations in histone retention develop and are associated with infertility.

Similar observations have also been provided for the development of differential DNA methylation regions (DMRs) induced by environmental toxicants such as DDT and vinclozolin. Since DHRs have a similar developmental programming, other epigenetic processes such as ncRNA are also anticipated to be similar.”

https://www.sciencedirect.com/science/article/pii/S0012160620301834 “Developmental origins of transgenerational sperm histone retention following ancestral exposures”

This study, like its dozens of predecessors performed year after year by this research facility, provided evidence for mechanisms of epigenetic transgenerational inheritance. The studied F3 generation members were great-grand-offspring, the first generation to have no direct exposure to DDT and vinclozolin.

As pointed out in A compelling review of epigenetic transgenerational inheritance:

“During the 1950s, the entire North American population was exposed to high levels of the pesticide DDT, when the obesity rate was < 5% of the population. Three generations later, the obesity frequency in North America is now ~45% of the population.”

There are varieties of mischaracterizations and hand-waving denials of epigenetically-inherited diseases. People don’t want to hear about and read proof that something we did or experienced disfavored our children, who unwittingly passed resultant problems on to their children, and which furthered on to their children’s children.

Transcendental experiences

gettingwell4 Just me

Among the everyday repetitive experiences and challenges, there are moments when I have to stop working, or pull into a parking lot, or just stop. Most of the time it’s when I’m listening to the transcendental music of Mozart written in the later years of his short life.

Start this next piece, and go about your business while listening. Even played at this modern pace, you may soon find the textures make you sit down, close your eyes, and wonder at places like from 12:00 to 12:30 and 22:30 to 23:00 what went on with Mozart and his audiences 233 years ago that evoked what’s still enjoyed today:

https://app.idagio.com/recordings/22495241

“I’ve been playing this symphony in the orchestra this week, alongside a symphony by Mozart’s contemporary, Antonio Salieri. It’s impossible to define fully what sets Mozart’s music apart from the well-crafted but ordinary Salieri. But the array of voices and motives swirling around in the “Prague” Symphony make this music come alive in a unique and sublime way.”

At other times, it’s listening to music Beethoven composed when he was almost deaf:

Hear the brook flow

Take responsibility for your one precious life – β glucan

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

From the main page of https://www.betaglucan.org/, a compilation for researchers:

“Beta Glucan extracted from yeast cell wall, can be a potent immune response potentiator and modulator. A common test to determine a glucan’s immune response potentiation effectiveness is the measure of the degree to which a glucan increases the nitric oxide burst, a pathogen killing agent.

Determinants of immune response activation and effectiveness are beta glucan source, processing, sizing and uniformity of beta glucan particles ingested. Particle size of 1-4 microns is optimum. Ingestion is optimized to prevent reaggregation.”

A sample of research:

“The tested (and suggested) daily dose remains in the range of 100–500 mg for stimulation of the immune system, whereas for a decrease in cholesterol levels a daily dose of 3 g is recommended.

Glucan supplementation prevents or even treats metabolic syndrome and decreases insulin resistance, dyslipidemia, and obesity. Glucan supplementation is a highly promising and inexpensive method of treatment for chronic respiratory problems.

Reactions known to be influenced by glucan are represented in white, reactions where glucan has no confirmed effects are shown in black.”

https://www.mdpi.com/1420-3049/24/7/1251/htm “Beta Glucan: Supplement or Drug? From Laboratory to Clinical Trials”

“Supplementation with glucan and vitamin D resulted in significant increase of vitamin D levels, improvements of HDL levels, and strong decrease of the total level of cholesterol.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5897984/ “Effects of β-glucan and Vitamin D Supplementation on Inflammatory Parameters in Patients with Diabetic Retinopathy”

“β-glucan inhibits tumor growth through induced systemic tumor-antigen specific T cell response, increased activity of T-cells in tumor, and decreased number of tumor-caused immunosuppressive cells. Sulforaphane inhibits CRC [colorectal cancer] carcinogenesis by modulating Nrf2 activity and inhibition of HDAC enzymes.

In a women’s health initiative prospective cohort during their 11.7-year follow up of dietary fiber and omega-3, -6 fatty acids, the results pointed out a reduced incidence of CRC for the association between a low dose of soluble fiber, a high dose of insoluble fiber, and a high dose of EPA and DHA.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321468/ “Chemoprevention of Colorectal Cancer by Dietary Compounds”

I first curated the above review and graphic in Train your immune system every day! 12 days into a self-quarantine after coming back from Milano, Italy, Monday, February 24, 2020. There’s a substantial probability that my traveling companion and I were exposed to COVID-19.

Yet neither of us had any symptoms then or since. My β-glucan, Vitamin D3, and zinc amounts were the same as described in that post, in Take responsibility for your one precious life – Vitamin D3, and in Take responsibility for your one precious life – Zinc.

Take responsibility for your one precious life – Vitamin D3

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

Where to start among 6,489 studies and reviews published during the past five years, results from a PubMed search of “dihydroxyvitamin D3.” How about:

“Vitamin D plays a fundamental role in body calcium and phosphorous homeostasis, ensuring proper functioning of the skeletomuscular system. Pleiotropic activities include:

  • Anti-inflammatory and immunomodulatory properties (predominantly downregulation of adaptive and upregulation of innate immunity);
  • An important role in reproduction, pregnancy, placental functions and fetal and child development;
  • Important in neurodevelopment as well as in the functioning of the adult central and peripheral nervous system;
  • Regulation of global metabolic and endocrine homeostasis and the functions of different endocrine organs, as well as in the functioning of the cardiovascular system;
  • Inhibits malignant transformation, tumor progression and has anti-cancer properties on a variety of tumors;
  • Formation of the epidermal barrier and hair cycling; and
  • Ameliorating effects on skin cancer and on proliferative and inflammatory cutaneous diseases.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342654/ “The serum vitamin D metabolome: What we know and what is still to discover”

Or maybe:

“A study in 6,275 American children and adolescents aged 1–21 years showed that 61% were 25-(OH)D3 insufficient and 9% deficient. In adults, up to 40% are 25-(OH)D3 insufficient and 6% deficient.

Once adequate vitamin D values are reached, to further preserve adequate vitamin D levels in adults, the IOM [Institute of Medicine] recommends a daily dose of 600 IU per day, while the Endocrine Society recommends a dose of 600–2000 IU per day (according to the amount of sunlight the individual is exposed to). There seems to be no additional health benefit in doses higher than 4000 IU/day.

Vitamin D supplementation was protective against acute respiratory tract infections in a 25-(OH)D3 deficient population, especially in those receiving daily or weekly supplementation. However, in children this protective effect could not be reproduced.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281985/ “Vitamin D’s Effect on Immune Function”

Not to forget Advanced glycation end products alter steroidogenic gene expression by granulosa cells: an effect partially reversible by vitamin D:

“This study suggests that there is a relationship between AGEs (advanced glycation end products) and their receptors (RAGE and sRAGE) with vitamin D. Understanding the interaction between AGEs and vitamin D in ovarian physiology could lead to a more targeted therapy for the treatment of ovarian dysfunction.”

Or similarities to broccoli sprouts’ main effect of Nrf2 signaling pathway activation:

“1,25(OH)2D3 plays a role in delaying aging by upregulating Nrf2, inhibiting oxidative stress and DNA damage, inactivating p53‐p21 and p16‐Rb signaling pathways, and inhibiting cell senescence and SASP.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516172/ “1,25‐Dihydroxyvitamin D exerts an antiaging role by activation of Nrf2‐antioxidant signaling and inactivation of p16/p53‐senescence signaling”

Why do we insist on giving ourselves non-communicable diseases?

I recently paid $22.53 after tax for a nearly two-year supply:

A better use of one’s money would be..?

My June 2020 serum 25-OH Vitamin D measurement was 76 on a scale of 0 to 100 from taking a total of 3,400 IU daily. It’s fat-soluble, so I take it along with 1 gram flax oil each time.

Take responsibility for your own one precious life.

What should be is different than what is

gettingwell4 Just me

A view from Hong Kong:

“If you read the explanations put forward by MMT advocates you could come away with the impression that the ‘theory’ is a discovery or original insight, but nothing could be further from the truth. What MMT actually does is employ accounting tautologies and a very superficial view of how monetary inflation affects the economy to justify theft on a grand scale.

When government creates money out of nothing and then exchanges that money for real resources, it is exchanging nothing for something. In effect, it is diverting resources to itself without paying for them. This is a form of theft, but it is surreptitious because the seller of the resources does not incur the cost of the theft.

MMT being bad from both ethical and economics perspectives probably won’t get in the way of its implementation. It has great appeal to the political class. For all intents and purposes MMT is already being put into practice in the US.

There is now a high probability of systemic collapse during this decade. What comes next could be worse.”

https://tsi-blog.com/2020/07/the-brave-new-world-of-mmt/ “The Brave New World of MMT”

Gold sniffs this out, rising from $1,400 to over $1,600, $1,700, $1,800, $1,900, $2,000 USD / oz. in 2020. How much higher will government theft take it?

mark-600x375

Image from Gold Switzerland.

Children playing with stacks of hyperinflated currency during the Weimar Republic, 1922

“Children playing with stacks of hyperinflated currency during the Weimar Republic, 1922” from Rare Historical Photos.

Take responsibility for your one precious life – Zinc

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

This 2020 review highlighted earlier clinical data on zinc:

  • “Zinc is known to modulate antiviral and antibacterial immunity and regulate inflammatory response.
  • Zinc possesses anti-inflammatory activity by inhibiting NF-κB signaling and modulation of regulatory T-cell functions.
  • The most critical role of zinc is demonstrated for the immune system.
  • Zinc regulates proliferation, differentiation, maturation, and functioning of leukocytes and lymphocytes.

Alteration of zinc status significantly affects immune response resulting in increased susceptibility to inflammatory and infectious diseases including acquired immune deficiency syndrome, measles, malaria, tuberculosis, and pneumonia. Zinc status is associated with the prevalence of respiratory tract infections in children and adults.

In view of the high prevalence of zinc deficiency worldwide (up to 17%), its impact on population health is considered as a significant issue. Certain groups of people, including infants, especially preterm ones, and elderly, are considered to be at high risk of zinc deficiency and its adverse effects.

Zinc was shown to have a significant impact on viral infections through modulation of viral particle entry, fusion, replication, viral protein translation and further release for a number of viruses including those involved in respiratory system pathology. Increasing intracellular Zn levels through application of Zn ionophores significantly alters replication of picornavirus, the leading cause of common cold.

The results of systematic analysis confirmed the efficiency of intake of at least 75 mg/day Zn in reduction of pneumonia symptom duration but not severity, with the response being more pronounced in adults than in children.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255455/ “Zinc and respiratory tract infections: Perspectives for COVID-19”

The review noted a 2014 rodent cell study which found:

“Labile zinc, a tiny fraction of total intracellular zinc that is loosely bound to proteins and easily interchangeable, modulates the activity of numerous signaling and metabolic pathways. Dietary plant polyphenols such as the flavonoids quercetin and epigallocatechin-gallate act as antioxidants and as signaling molecules. The activities of numerous enzymes that are targeted by polyphenols are dependent on zinc.

We have demonstrated the capacity of quercetin and epigallocatechin-gallate to rapidly increase labile zinc. The polyphenols transport zinc cations across the plasma membrane independently of plasma membrane zinc transporters.

The ionophore activity of dietary polyphenols may underlay the raising of labile zinc levels triggered in cells by polyphenols and thus many of their biological actions.”

https://pubs.acs.org/doi/10.1021/jf5014633 “Zinc Ionophore Activity of Quercetin and Epigallocatechin-gallate: From Hepa 1-6 Cells to a Liposome Model” (not freely available)

I get EGCG from drinking 4-5 cups of green tea every day, and 65 mg zinc from supplements. Microwave broccoli to increase flavonoid levels demonstrated 108.5% to 129.8% increases in quercetin and kaempferol levels from microwaving grocery-store broccoli. Microwaving 3-day-old broccoli sprouts may be expected to increase my worst-case calculation of daily 134 mg total flavonoids.

I’ve taken quercetin intermittently per Preliminary findings from a senolytics clinical trial. I’m changing that to take 100 mg quercetin daily.

Take responsibility for your own one precious life.