Precondition your defenses with broccoli sprouts

This 2020 human cell study elaborated on mechanisms mentioned in Eat broccoli sprouts for your hearing and Sulforaphane in the Goldilocks zone:

“NFE2L2/NRF2, a transcriptional factor that controls expression of multiple detoxifying enzymes through antioxidant response elements (AREs), is a target of sulforaphane (SFN). NFE2L2/NRF2 is a target gene of TFEB (transcription factor EB), a master regulator of autophagic and lysosomal functions, which we show here to be potently activated by SFN.

SFN induces TFEB activation by stimulating a moderate increase in reactive oxygen species (ROS). Subsequently, cells are preconditioned to activate a self-defense mechanism that protects against oxidative damage.

TFEB activity is required for SFN-induced protection against both acute oxidant bursts and chronic oxidative stress. By simultaneously activating macroautophagy / autophagy and detoxifying pathways, natural compound SFN may trigger a self-defense cellular mechanism that can effectively mitigate oxidative stress commonly associated with many metabolic and age-related diseases.


SFN-induced TFEB nuclear accumulation was completely blocked by pretreatment of cells by N-acetyl-cysteine (NAC), or by other commonly used antioxidants. NAC also blocked SFN-induced mRNA expression of TFEB target genes, as well as SFN-induced autophagosome formation.

SFN offers an exceptional therapeutic opportunity for many metabolic and age-related diseases, in which oxidative stress and impaired autophagy both contribute to pathologies.” “Sulforaphane activates a lysosome-dependent transcriptional program to mitigate oxidative stress”

This study explored cell mechanisms and confirmed opposing effects of NAC. I dropped NAC supplementation 62 weeks ago during Week 1 of eating broccoli sprouts every day, and dropped other antioxidants later.


Osprey breakfast

Part 2 of Eat broccoli sprouts for your hearing

Went to a free hearing test at Costco this week. Results weren’t significantly different than those from a doctor’s office 2.5 years ago:


Didn’t have many expectations, other than I’d be given a hard sell to buy hearing aids by a technician on commission. A young woman used several sales techniques which I was prepared for, and doubled down when I didn’t answer leading questions to her satisfaction.

The second study of Part 1 offered evidence that “The antioxidant pathway was difficult to be activated in the context of accumulation of ROS.” Other studies I’ve read but haven’t curated indicated that there weren’t effective treatments once hearing damage had occurred.

When you get exposed to loud noises, do your best to immediately mitigate that by enhancing your overall Nrf2 gene expression. Timely Nrf2 activation can fix hearing damage.

A curious deficiency of reactive oxygen species accumulated in the inner ear to sufficiently activate Nrf2 doesn’t happen in other parts of our bodies. I’ll guess that hearing loss may exist to turn old mammals into prey, as part of evolutionarily-determined limits on lifespan that protect against population overshoot. Take responsibility for your own one precious life.

Broccoli sprouts positively influence Sestrin proteins

Four papers on Sestrin, with the first a 2021 review:

“Sestrin 2 (Sesn2) is a member of the evolutionarily conserved and stress-inducible sestrin family. In mammals, this family is composed of Sesn1–3, and Sesn2 is the main member that responds to oxidative stress.

Sesn2 inhibits mammalian target of rapamycin (mTOR)-mediated cell over-proliferation by activating adenosine monophosphate-activated protein kinase (AMPK) and its kinase activity. Sesn2 also regulates redox balance by directly exerting antioxidant enzyme activity and regulating antioxidant signaling.

Inflammation, which is not regulated by oxidative stress, also plays an important role in cardiovascular diseases (CVDs). Sesn2 is involved in inflammation and immune regulation in many systems.

There is a positive feedback loop between Sesn2 and Nrf2:

sestrin2 nrf2

Sesn2 and p62 are expressed under oxidative stress. Sesn2 binds to ULK1 and p62 to form a functional complex, which promotes p62 phosphorylation, promoting p62-dependent autophagy degradation of Keap1.

Consequently, Nrf2 accumulates in cells, transfers to the nucleus, and promotes transcriptional activation of genes controlled by antioxidant response elements (ARE).

Circulating Sesn2 levels are elevated in a variety of CVDs, such as coronary heart disease, heart failure and atrial fibrillation, which indicates that Sesn2 is induced and plays a protective role in CVDs.” “Sestrin 2, a potential star of antioxidant stress in cardiovascular diseases” (not freely available)

A second paper was also a 2021 review:

“Sestrin2 acts as an antioxidant protein that diminishes accumulation of ROS and inhibits mTORC1 signaling. Both accumulation of ROS and activation of mTORC1 are associated with aging and age-related diseases.

Since plasma sestrin2 levels in patients with CAD and those with carotid atherosclerosis were shown to be high, it remains unclear whether or not an exogenous administration of sestrin2 could be beneficial for prevention of atherosclerotic disease.” “The Protective Role of Sestrin2 in Atherosclerotic and Cardiac Diseases”

A third paper was a 2020 human study:

“Sesn 1 and Sesn 2 levels were significantly reduced in sarcopenic compared to non-sarcopenic subjects. It can be concluded that sarcopenia can be diagnosed at the early stage by using serum sestrin as one potential biomarker.” “Serum sestrins: potential predictive molecule in human sarcopenia” (not freely available)

A fourth paper was a 2020 rodent study:

“Sulforaphane (SFN) alleviated hematological variations, oxidative stress, heart dysfunction and structure disorder, and cardiomyocyte apoptosis induced by potassium dichromate. Moreover, SFN:

  • Reduced p53;
  • Cleaved caspase-3, Bcl2-associated X protein, nuclear factor kappa-B, and interleukin-1β levels; and
  • Increased Sesn2, Nrf2, heme oxygenase-1, NAD(P)H quinone oxidoreductase-1; and
  • Phosphorylated AMPK levels.

This study demonstrated that SFN ameliorates Cr(VI)-induced cardiotoxicity via activation of the Sesn2/AMPK/Nrf2 signaling pathway.” “Sulforaphane attenuates hexavalent chromium-induced cardiotoxicity via the activation of the Sesn2/AMPK/Nrf2 signaling pathway” (not freely available)

I found these studies as well as the previous post Cow milk causes disease from their citing a 2015 study The antioxidant function of sestrins is mediated by promotion of autophagic degradation of Keap1 and Nrf2 activation and by inhibition of mTORC1 (not freely available).

Cow milk causes disease

This 2021 review followed up Epigenetic effects of cow’s milk and many papers since then:

“Epidemiological studies associate intake of cow milk with an increased risk of diseases, which are associated with overactivated mechanistic target of rapamycin complex 1 (mTORC1) signaling. Milk’s physiological function to maintain high mTORC1 signaling at the beginning of mammalian life turns into adverse health effects when this postnatal endocrine and epigenetic system is not discontinued as designated by physiological processing of the lactation genome.

Milk is a signaling interface between the maternal lactation genome and the infant’s cellular mTORC1 system that orchestrates growth, anabolism, metabolic, immunological, and neurological programming. Pasteurization combined with refrigeration exposed human milk consumers to bioactive milk exosome (MEX)-derived micro-ribonucleic acids (miRs), augmenting milk’s mTORC1 activity compared to boiled, ultra-heat-treated, or fermented milk.

milk-mediated mTORC1 signaling

Milk consumption activates five major pathways stimulating mTORC1 via:

  1. Growth factors, including growth hormone, insulin, and insulin-like growth factor 1;
  2. Amino acids, especially branched-chain amino acids;
  3. Milk fat-derived palmitic acid;
  4. Milk sugar lactose; and
  5. Epigenetic modifiers, especially MEX-derived miRs.

Understanding milk’s interaction with the central hub of metabolic regulation, mTORC1, will open new avenues for prevention of common diseases.” “Lifetime Impact of Cow’s Milk on Overactivation of mTORC1: From Fetal to Childhood Overgrowth, Acne, Diabetes, Cancers, and Neurodegeneration”

This reviewer is somewhat of a zealot. Still, he cited 555 references.

His genotype may tolerate lactose, but he didn’t argue for it:

“After breast feeding, mucosal expression of lactase, an intestinal enzyme hydrolyzing lactose into glucose and galactose, is downregulated in all mammals with the exception of Neolithic humans, who developed LCT [lactase gene] mutations allowing persistent lactase expression.

Lactose content of milk makes up around 2–8% by weight. Lactose hydrolysis provides glucose and galactose, which both activate mTORC1:

  • During glucose abundance and glycolysis, sufficient cellular energy is produced in the form of ATP, which suppresses AMPK activity. Aldolase operates as a sensor for glucose availability that directly links glucose shortage to activation of AMPK.
  • Galactose via induction of oxidative stress activates mTORC1. Galactose-induced overactivation of mTORC1 promotes senescence of neural stem cells and aging of mesenchymal stem cells.

Lactobacilli used in food and dairy fermentation increase NRF2 activation, resulting in NRF2-induced sestrin expression, which attenuates mTORC1 activation.”

Basal cognition

To follow up Electroceuticals, a 2021 article by Dr. Michael Levin:

“A key philosophical idea, borrowed from computer science, is substrate independence. Components of a living system can carry out appropriate, clearly specified cognitive functions.

Cognitive processes in embryogenesis and regeneration:


    • (a) An egg will reliably give rise to a species-specific anatomical outcome.
    • (b) This process is usually described as a feed-forward system where activity of gene-regulatory networks (GRNs) within cells results in expression of effector proteins that, via structural properties of proteins and physical forces, will result in the emergence of complex shape. This class of models (bottom-up process driven by self-organization and parallel activity of large numbers of local agents) is difficult to apply to several biological phenomena. Regulative development can alter subsequent steps to reach the correct anatomical goal state despite drastic deviations of the starting state.
    • (c) For example, mammalian embryos can be divided in half, giving rise to perfectly normal monozygotic twins, each of which has regenerated the missing cell mass.
    • (d) Mammalian embryos can also be combined, giving rise to a normal embryo in which no parts are duplicated.
    • (e) Such capabilities suggest that pattern control is fundamentally a homeostatic process—a closed-loop system using feedback to minimize error (distance) between a current shape and a target morphology. Although these kinds of decision-making models are commonplace in engineering, they are only recently beginning to be employed in biology. This kind of pattern-homeostatic process must store a setpoint that serves as a stop condition; however, as with most types of memory, it can be specifically modified by experience.
    • (f) In the phenomenon of trophic memory, damage created at a specific point on the branched structure of deer antlers is recalled as ectopic branch points in subsequent years’ antler regeneration. This reveals ability of cells at the scalp to remember spatial location of specific damage events and alter cell behaviour to adjust the resulting pattern appropriately—a pattern memory that stretches across months of time and considerable spatial distance and is able to modify low-level (cellular) growth rules to construct a pre-determined stored pattern that differs from genome-default for this species.
    • (g) A similar capability was recently shown in a molecularly tractable model system, in which genetically normal planarian flatworms were bioelectrically reprogrammed to regenerate two-headed animals when cut in subsequent rounds of asexual reproduction in plain water.
    • (h) The decision making revealed by cells, tissues and organs in these examples of dynamic remodelling toward specific target states could be implemented by cybernetic processes at various positions along a scale of proto-cognitive complexity.

A challenge for the field of basal cognition is to reveal gradualism of cellular properties underwriting this critical biological function to leverage an understanding of clear phase transitions observed in cognitive capacities. The origin and development of nervous systems is so far the most dramatic example.” “Uncovering cognitive similarities and differences, conservation and innovation”

Why aren’t more resources being directed toward these research efforts? Glad to see that at least one co-founder of Microsoft, Paul Allen, posthumously used his billions to sponsor science for human good.

Eat broccoli sprouts for your hearing

Two 2021 papers, both of which I found by each citing a 2009 Molecular mechanisms underlying cochlear degeneration in the tubby mouse and the therapeutic effect of sulforaphane (not freely available). First was a review:

“Hair cell damage and loss mediated by oxidative stress are important causes of hearing loss. Sensorineural hearing loss is the most common type of hearing loss, including noise induced hearing loss (NIHL), age-related hearing loss (ARHL), and ototoxic hearing loss.

Nrf2 reduces cell damage caused by oxidative stress, and maintains the dynamic balance of systematic redox by inducing and regulating expression of various antioxidant factors. This review summarizes correlation studies of Nrf2 in hearing loss, providing ideas for prevention and treatment of hearing loss with Nrf2 as the target.


There is positive feedback between p62-mediated autophagy and Nrf2. p62 promotes accumulation of Nrf2 and nuclear translocation. Concurrently, increased Nrf2 promotes p62 expression.

How Nrf2 regulates ROS changes in hair cells, and the upstream and downstream regulatory network of Nrf2 in hair cells, are still not fully understood. Studies on early prevention and treatment of hearing loss through the Keap1-Nrf2-ARE [antioxidant response element] signaling axis are still at the exploratory stage.” “The Role of Nrf2 in Hearing Loss”

Second paper was a rodent study:

“We examined oxidative stress and antioxidant response of the p62-Keap1-Nrf2 pathway in cochleae during age-related hearing loss (ARHL) and noise-induced hearing loss (NIHL). We elucidated the function of full-length and variant p62/Sqstm1 (referred to here as p62) in regulation of Nrf2 activation.

Cochlear damage was assessed by analyzing auditory brainstem response (ABR) and by counting hair cells (HCs). Malondialdehyde (MDA, a lipid peroxidation product) levels were measured in young and old mice to determine whether oxidative stress contributed to ARHL.

auditory brainstem response

  • (A) Audiometric threshold (dB) determined from click and pure tone evoked ABRs. Thresholds were each significantly different (P < 0.001) between young mice and old mice.
  • (B) HC loss percentage in basal cochlear turns. Significant differences (P < 0.001) were observed between young and old mice.
  • (C) MDA levels in the cochleae of old mice were significantly higher (P = 0.034) than those of young mice.

ROS accumulation is closely related to ARHL and NIHL. The inability of ROS accumulation to activate the Nrf2 antioxidant stress pathway under physiological conditions may be related to alternative splicing of p62 mRNA in cochleae.

However, the agonist of the Nrf2 pathway enhanced Nrf2 nuclear translocation. This suggests a mechanism in which the antioxidant pathway was difficult to be activated in the context of accumulation of ROS.” “New Target of Oxidative Stress Regulation in Cochleae:Alternative Splicing of the p62/Sqstm1 gene”

The study’s two-month-old mice were equivalent to a 20-year-old human. Its 13-to-14-month-old mice were equivalent to humans in their 60s to 70s.

I expected preconditioning to be mentioned in both papers. Maybe these researchers thought it was too obvious and didn’t need to be stated that:

  • Repeated use of a Nrf2 activator produces transient mild stress;
  • Which elicits a stronger response; and
  • Preconditions cells for future stress?

Sulforaphane in the Goldilocks zone and its cited papers exhaustively emphasized preconditioning’s importance. The main thing I’m trying to do with isothiocyanates is to send a weak pro-inflammatory signal to my endogenous ARE system to exercise natural defenses.

Twice-daily drills make me more proficient at responding to actual emergencies. Post-drill, my body recycles material to be ready to respond the next time.

I do the same thing once a day with β-glucan 1,3/1,6 to train my innate immune system. Microphages in my gut are the first responders. Like the very reactive isothiocyanates, I don’t take anything with, or an hour before or after β-glucan 1,3/1,6.

Why tolerate “the antioxidant pathway was difficult to be activated in the context of accumulation of ROS” when a sulforaphane “agonist of the Nrf2 pathway enhanced Nrf2 nuclear translocation”? For all we know, diminished natural defenses and hearing loss may exist to turn old mammals into prey.

Continued in Part 2.

Part 3 of Broccoli sprouts activate the AMPK pathway

This 2020 cell study investigated sulforaphane and three transcription pathways:

“Novel findings of this study are:

  1. AMPK controls only a subset within the Nrf2-dependent transcriptome;
  2. Altered Nrf2 levels or altered accessibility of regulatory ARE sites do not account for observed differences in target gene transcription between used wt and AMPK −/− cells;
  3. Rather, AMPK presence/activity ensures reduced Bach1 abundance with preferential Nrf2 over Bach1 binding to regulatory ARE sites, and finally stronger transactivation of selected target genes; and
  4. AMPK negatively controls bach1 mRNA expression.


In AMPK−/− cells, levels of BTB and CNC homology 1 (Bach1), a competitor of Nrf2 for ARE sites with predominant repressor function, were higher. Bach1 also bound to a greater relative extent to the examined ARE sites when compared to Nrf2.

Observed AMPK-mediated boost in transactivation of a subset of Nrf2 target genes involves downregulation of Bach1 and subsequent favored binding of activating Nrf2 over repressing Bach1 to examined ARE sites.


The discovered link between AMPK and Bach1 as well as the resulting selective influence on Nrf2 target gene expression are compelling and touch existing data:

  • Bach1 contributed to expression of only selected Nrf2 target genes in endothelial cells under hypoxic conditions which, in turn, are known to influence AMPK activity.
  • Bach1 levels are elevated during aging, in metastatic lung tumors or triple negative breast tumors with concomitant mitochondrial dysfunction, all events also partly connected with AMPK- and/or Nrf2 activity.

These issues strongly advocate for a closer look into interplay between cellular sensors and executors of the oxidative/xenobiotic and metabolic stress response, which likely will uncover additional layers of regulation of cellular stress resilience.” “AMPK Enhances Transcription of Selected Nrf2 Target Genes via Negative Regulation of Bach1”

This study hasn’t been cited even once since it was published eleven months ago. These researchers did a very good job of producing evidence for mechanisms of signaling pathways competing with and complementing each other.

This study provided further details to support Broccoli sprouts activate the AMPK pathway findings that sulforaphane first activates the AMPK pathway on the way to its main effect of Nrf2 pathway activation:

figure 8


To follow up A top-down view of biological goal-directed mechanisms, 2020 and 2021 presentations by Dr. Michael Levin of Tufts University:

“We want to able to design a living form at the level of anatomy, and have the system compile it down into a set of low level instructions that you would have to give to the cellular collective to make it do this. What we would like to do is to offload all that complexity onto cells, and control this  whole thing with inputs, experiences, or stimuli.

What evolution does is to exploit bioelectricity to implement networks that store these patterns, patterns that serve as memories and goal states.”


Appreciate Dr. Levin sticking with his findings for three decades now. Credit my son for refreshing my memory.

Eat mushrooms for a longer life?

Two papers, starting with a 2021 meta-analysis of mushroom intake:

“Mushroom consumption was associated with a lower risk of total mortality in this nationally representative sample of US adults.

median mushroom intake

15,546 participants were included, mean age 44.3 years. During a mean follow-up duration of 19.5 years, a total of 5,826 deaths were documented.

Participants who reported consuming mushrooms had lower risk of all-cause mortality compared with those without mushroom intake after adjusting for demographic, major lifestyle factors, overall diet quality, and other dietary factors including total energy.” “Association of mushroom consumption with all-cause and cause-specific mortality among American adults: prospective cohort study findings from NHANES III”

A 2019 review with two of the same coauthors:

“Mushrooms are inherently, or can easily be made to be, excellent dietary sources of 4 important bioactive compounds that decrease in humans as they age:

  • Selenium;
  • Vitamin D2;
  • Glutathione; and
  • Ergothioneine (Ergo).

All of these except for Ergo can be found in significant amounts in other foods, and mushrooms are by far the best human dietary source.

Humans produce a highly specific transport protein for Ergo that makes it highly bioavailable and avidly retained. Such specific transporters are rarely present for nonnutrient bioactive compounds.

mushroom ergothioneine glutathione

Mushrooms are a valuable source of protein, fiber, B vitamins, phenolic compounds, potassium, and β-glucans. An increase of 3 mg/d can be accomplished by consumption of about 100 g of fresh button mushrooms per day, or around 25 g of fresh specialty mushrooms such as shiitake, oyster, or maitake mushrooms.

One potential way to add fresh button mushrooms to the diet would be to embrace the meat-blend approach in which about 30% to 40% ground, fresh button mushrooms are blended with 60% to 70% ground beef to replace pure ground beef in burgers or other common commonly consumed dishes. Another approach could be to use small amounts of Ergo-rich specialty mushroom dried powder as a new food ingredient into current or new food products.” “Micronutrients and Bioactive Compounds in Mushrooms: A Recipe for Healthy Aging?” (not freely available)

I doubt that mushroom intake was a cause of more than a third of this meta-analysis’ participants dying before they reached age 64. The first study of The amino acid ergothioneine had better methodological approaches that related mushroom intake to mortality.

I’ve eaten more than triple the first graphic’s 72 grams for over a year, not because I knew of health effects, but because I like mushrooms. The second graphic is nice to know, but probably won’t go out of my way for ergothioneine content.

Brown your white fat cells with broccoli sprouts

A 2021 rodent study and a blog post with 51 references investigated fat cells:

“Sulforaphane (SFN) is a potent indirect antioxidant and a promising agent for controlling metabolic disorder disease. We evaluated efficacy of SFN against high fat diet (HFD)-induced-obesity mice, and investigated potential mechanisms.


  • Suppressed HFD-induced body weight gain;
  • Reduced fat cell [adipocyte] size;
  • Suppressed expression of key genes in adipogenesis;
  • Inhibited lipid accumulation in C3H10T1/2 [pre-adipocyte] cells;
  • Increased expression of brown adipocyte-specific markers and mitochondrial biogenesis in vivo and in vitro; and
  • Decreased cellular and mitochondrial oxidative stress.

sulforaphane influences fat cells

Gene expression profile of C3H10T1/2 cells after SFN treatment showed that SFN inhibited expression of core adipogenesis genes (Ppar-γ, Fas, Cebpβ and Scd1) and enhanced expression of browning genes (Chop, Temem 26, Ucp1, Pgc-1α, and Prdm16) in adipocyte differentiation and trans-differentiation. This result suggested possible conversion of white adipocytes into beige cells.

We report that SFN induces browning of mature C3H10T1/2 adipocytes based on promotion of mitochondrial biogenesis by means of upregulation of the AMPK and NRF2 signaling pathways, and enhancement of mitochondrial function. Our further research revealed that SFN can prevent HFD-induced obesity in C57BL/6N mice by inducing browning of white adipose tissue.” “The Protective Effects of Sulforaphane on High-Fat Diet-Induced Obesity in Mice Through Browning of White Fat”

Dr. Paul Clayton had a nuanced view of body fat and its browning:

“You can divide adipose tissue into three cell types:

  • White adipocytes account for 95% of all adipocytes and have a primarily storage function;
  • The primary function of brown adipocytes, which range from 1-5% depending on cold exposure and very specific types of chemo-stimulation i.e. β3-adrenergic, is generation of heat via mitochondrial uncoupling.
  • Beige adipocytes are intermediate. They aren’t interspersed in depots of white adipose tissue and can transform into brown-like adipocytes following cold exposure or adrenergic stimulation.

Bone marrow adipose tissue plays an important role in haematopoiesis and bone metabolism in more than one form:

  • One is located in distal bones (forearm and lower leg) and is pretty much stable;
  • The other form is in spine and proximal limb bones, and is inducible by environmental factors such as cold exposure, fasting, and anaemia.

White adipose tissue can be divided into visceral and sub-cutaneous deposits, and these tissues have different behaviours and functions, too.

From a clinical perspective, it’s important to know that adipocyte-related inflammatory effects can be neutralised with omega 3 fatty acids, which return fat cells to a ‘healthy’ configuration. Their inflammatory effects can also be inhibited by various polyphenols which, among other things, block release of pro-inflammatory microRNAs.

In my experience, combining omega 3s with lipophile polyphenols and AMPK-activators such as dammarane saponins and metformin, provide supra-additive benefits.” “Turn Fat into Muscle”

Still no mention of sulforaphane on the doctor’s blog, although it’s:

I came across this first study through a “PPAR sulforaphane” search. Discarding a supplement as a result, because I’m already doing enough!


The amino acid ergothioneine

A trio of papers on ergothioneine starts with a 2019 human study. 3,236 people without cardiovascular disease and diabetes mellitus ages 57.4±6.0 were measured for 112 metabolites, then followed-up after 20+ years:

“We identified that higher ergothioneine was an independent marker of lower risk of cardiometabolic disease and mortality, which potentially can be induced by a specific healthy dietary intake.

overall mortality and ergothioneine

Ergothioneine exists in many dietary sources and has especially high levels in mushrooms, tempeh, and garlic. Ergothioneine has previously been associated with a higher intake of vegetables, seafood and with a lower intake of solid fats and added sugar as well as associated with healthy food patterns.” “Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease”

I came across this study by its citation in a 2021 review:

“The body has evolved to rely on highly abundant low molecular weight thiols such as glutathione to maintain redox homeostasis but also play other important roles including xenobiotic detoxification and signalling. Some of these thiols may also be derived from diet, such as the trimethyl-betaine derivative of histidine, ergothioneine (ET).

image description

ET can be found in most (if not all) tissues, with differential rates of accumulation, owing to differing expression of the transporter. High expression of the transporter, and hence high levels of ET, is observed in certain cells (e.g. blood cells, bone marrow, ocular tissues, brain) that are likely predisposed to oxidative stress, although other tissues can accumulate high levels of ET with sustained administration. This has been suggested to be an adaptive physiological response to elevate ET in the damaged tissue and thereby limit further injury.” “Ergothioneine, recent developments”

The coauthors of this review were also coauthors of a 2018 review:

“Ergothioneine is avidly taken up from the diet by humans and other animals through a transporter, OCTN1. Ergothioneine is not rapidly metabolised, or excreted in urine, and has powerful antioxidant and cytoprotective properties.

ergothioneine in foods

Effects of dietary ET supplementation on oxidative damage in young healthy adults found a trend to a decrease in oxidative damage, as detected in plasma and urine using several established biomarkers of oxidative damage, but no major decreases. This could arguably be a useful property of ET: not interfering with important roles of ROS/RNS in healthy tissues, but coming into play when oxidative damage becomes excessive due to tissue injury, toxin exposure or disease, and ET is then accumulated.” “Ergothioneine – a diet-derived antioxidant with therapeutic potential”

I’m upping a half-pound of mushrooms every day to 3/4 lb. (340 g). Don’t think I could eat more garlic than the current six cloves.


I came across this subject in today’s video:

Foods for your vision

This 2021 review by five ophthalmologists and two researchers characterized findings of food effects on human vision:

“The most challenging ocular disorders are uncorrected / under-corrected refractive errors, ocular surface dysfunction / dry eye disease, cataracts, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD):

  • Severe visual impairment and blindness due to cataract or refractive error constitutes half of all global cases;
  • Glaucoma is the most common cause of irreversible blindness;
  • DR is the first cause of visual disability in working-age adults; and
  • AMD is the first cause of blindness in the elderly.

We identify directions for further research on:

  • The role of diet and nutrition in eyes and vision;
  • Potential antioxidant, anti-inflammatory, and neuroprotective effects of natural food (broccoli, saffron, tigernuts and walnuts);
  • The Mediterranean Diet; and
  • Nutraceutic supplements that may supply a promising and highly affordable scenario for patients at risk of vision loss.

We improve understanding of natural food nutritional hallmarks, benefits of the MedDiet, and appropriate oral supplements with vitamins, carotenoids and PUFAs for better eye and vision care.” “Searching for the Antioxidant, Anti-Inflammatory, and Neuroprotective Potential of Natural Food and Nutritional Supplements for Ocular Health in the Mediterranean Population”



Are you prepared?

“There is one type of inflation that the Fed has never had control over – as covered in the previous analysis – inflation caused by shortages and supply side shocks. To fix that kind of inflation requires fixing the physical shortage problem. We’re seeing this right now with the 12 month increase in prices of imports going up by 10.6%.

This isn’t just theory. It is our collective history. Persistent and difficult to overcome inflation was what happened in the late 1970s and early 1980s.

It seems almost like lost knowledge for many today, who are focused on the easier to understand concept of inflation created by excess money creation. What happened in practice was a different source of rising prices. The last time this happened it took decades to fully break the inflationary cycle.” “Climate Change & Court-Ordered Inflation”

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

Does sulforaphane treat autism?

A 2021 human study investigated sulforaphane treatments of autistic 3-to-12-year-olds:

“Sulforaphane (SF) led to non-statistically significant changes in the total and all subscale scores of the primary outcome measure. Several effects of SF on biomarkers correlated to clinical improvements. SF was very well tolerated and safe and effective based on our secondary clinical measures.


Clinical response to SF was associated with changes in mitochondrial function, and large intrasubject variability in this study was linked to underlying biological responses. The increase in ATP [adenosine triphosphate]-Linked Respiration associated with improvement in ABC [Aberrant Behavior Checklist] scores suggests that those individuals who showed improvements in behavior also had improved mitochondrial capacity to produce ATP.

Individuals who showed an improvement in ABC scores also showed a decrease in Proton Leak Respiration, suggesting that their mitochondria were better able to regulate oxidative stress. It is also possible that the increase in ATP production was related to improvement in the ability of mitochondria to handle oxidative stress.

SF had significant positive effects on oxidative stress, cytoprotective markers and cytokines, as well as mitochondrial function. These were promising findings that require further investigation of both clinical effects and mechanisms of action of SF.” “Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder”

Differences between this clinical trial and its pilot study curated in Autism biomarkers and sulforaphane included:

“HO-1 [heme oxygenase 1] functions to couple activation of mitochondrial biogenesis to anti-inflammatory cytokine expression. It was initially increased in the pilot study, then paradoxically decreased in the main study, on continued treatment for longer periods with SF.

Increased HO-1 is consistent with decreases in proinflammatory cytokines we observed initially in IL-6, IL-1β and TNF-α. Decreased levels of cytokines continued after HO-1 returned to baseline with longer duration of treatment and suggest a decreased inflammatory state.

These cytokines are usually elevated in children with ASD, but were decreased on treatment with SF: IL-6 and TNF-α at 15 (but not 30) weeks.”

This study made a good effort with autistic children. Its insignificant effects of sulforaphane treatments pointed toward an understanding that human experiences when we are fetuses can override many subsequent events, treatments, and life experiences.