Take responsibility for your one precious life – DHEA

This 2020 meta-analysis subject was DHEA:

“Twenty-four qualified trials were included in this meta-analysis. Statistically significant increases in serum IGF-1 levels were found only in participants who were:

  1. Women; or
  2. Supplementing 50 mg/d; or
  3. Undergoing intervention for > 12 weeks; or
  4. Without an underlying comorbidity; or
  5. Over the age of 60 years.

DHEA supplementation led to an overall increase of ~16 ng/ml in serum IGF-1 levels, as well as increases of ~23 [women] and ~20 ng/ml [age > 60]. Diseased and healthy subjects ages ranged from 20 to 72 years old.”

Discussion section explanations of the above:

  1. “Women are more susceptible to biochemical and clinical shifts caused by DHEA supplementation.
  2. The majority of investigations tested DHEA at a dose of 50 mg/d.
  3. The majority of studies were performed for > 12 weeks.
  4. Participants with no comorbidities were also older in many studies.
  5. Older patients have a natural decline in the production of IGF-1 and DHEA.

Additional rigorous RCTs are warranted to better define whether and to what extent changes in IGF-1 levels caused by DHEA supplementation are relevant for health benefits.”

https://www.sciencedirect.com/science/article/abs/pii/S0531556520302977Impact of dehydroepianrosterone (DHEA) supplementation on serum levels of insulin-like growth factor 1 (IGF-1): A dose-response meta-analysis of randomized controlled trials” (not freely available)


More on IGF-1 from The influence of zinc supplementation on IGF-1 levels in humans: A systematic review and meta-analysis which was cited for “Previous studies have demonstrated that IGF-1 levels can be affected by several factors.”

“IGF-1 is a growth factor synthesized in the liver, and elicits a myriad of effects on health due to its participation in the GH-IGF-1 axis, where it:

  • Is involved in tissue homeostasis;
  • Has anti-apoptotic, mitogenic, anti-inflammatory, antioxidant and metabolic actions;
  • Contributes to skeletal muscle plasticity, maintenance of muscle strength and muscle mass;
  • Neural and cardiovascular protection;
  • Development of the skeleton;
  • Possesses insulin-like effects, and
  • Is a key factor in brain, eye and lung development during fetal development.

IGF-1 plays important roles in both growth and development, and its levels vary depending on age, with peaks generally observed in the postnatal period and at puberty. IGF-1 levels influence the release of GH [growth hormone] from the hypophysis [pituitary gland] via a negative feedback loop.

A rapid decrease in IGF-1 levels is registered during the third decade of life. Levels gradually decrease between the third and the eighth decade of life.”


The Group 3 “> 12 weeks” finding was reinforced by perspectives such as:

Group 4 “with no comorbidities” was narrowly defined. All of us have degrees of diseases in progress. Consider aging effects:

  • Aging as a normal disease “Aging and its diseases are inseparable, as these diseases are manifestations of aging. Instead of healthy aging, we could use the terms pre-disease aging or decelerated aging.”
  • Aging as an unintended consequence “Epigenetic ageing begins from very early moments after the embryonic stem cell stage and continues uninterrupted through the entire lifespan. Ageing is an unintended consequence of processes that are necessary for development of the organism and tissue homeostasis thereafter.”
  • Organismal aging and cellular senescence “If we assume that aging already starts before birth, it can be considered simply a developmental stage, required to complete the evolutionary program associated with species-intrinsic biological functions such as reproduction, survival, and selection.”
  • An environmental signaling paradigm of aging “The age-phenotype of a cell or organ depends on its environment and not its history. Organisms, organs, and their cells can be reset to different age-phenotypes depending on their environment.”

These perspectives are less important than what each of us choose to do about our own problems. Take responsibility for your one precious life.

Get serious about advanced glycation end products (AGEs)

Ever heard about AGEs? Here are three papers that describe how AGEs affect humans.

First is a 2020 Italian review Common Protective Strategies in Neurodegenerative Disease: Focusing on Risk Factors to Target the Cellular Redox System:

“Neurodegenerative disease is an umbrella term for different conditions which primarily affect the neurons in the human brain. Currently, neurodegenerative diseases are incurable, and the treatments available only control the symptoms or delay the progression of the disease.

Neurotoxicity can be induced by glycation reactions. Since glycation is a nonenzymatic process, proteins characterized by a slow turnover are those that more easily accumulate AGEs.

Methylglyoxal (MG) can occur as glycolysis by-product, but it is also present in foods (especially cooked and baked), beverages (mainly those fermented), and cigarette smoke, and it is considered the most potent precursor of AGE formation. More than 20 different AGEs have been identified in foods and in human tissues.

AGE accumulation, oxidative stress, and inflammation are related to AGE ability to bind specific receptors called RAGE. RAGE expression increases during aging, cancer, cardiovascular diseases, AD [Alzheimer’s], PD [Parkinson’s], and other neurodegenerative diseases.”


A 2015 study by some of the same authors Antiglycative activity of sulforaphane: a new avenue to counteract neurodegeneration? was cited for a treatment in addition to changing one’s diet to be AGE-less.

“When MG production is increased by high glucose or oxidative stress, glycated proteins accumulate in the brain and lead to glycative stress, playing a fundamental role in the establishment of different neurodegenerative disorders.

Our results indicated that SF [sulforaphane] counteracts ROS by two possible mechanisms of action: an increase of intracellular GSH [glutathione] levels and an enhancement of MG-detoxification through the up-regulation of the glyoxalase (GLO1) systems. GLO1 up-regulation is mediated by the transcription factor Nrf2. SF has been demonstrated to activate Nrf2.

Another mechanism by which SF exerts its neuroprotective activity against MG-induced glycative damage is the modulation of mitogen-activated protein kinase (MAPK) signaling pathways involved in apoptotic cell death. All MAPK signaling pathways are activated in AD.

Brain-derived neurotrophic factor (BDNF) is associated with neuronal survival through its interactions with the tyrosine receptor kinase B (TrkB) and p75 cellular receptors. BDNF expression levels are reduced in the brain of AD patients. SF pre-treatment, before MG addition, not only further increased BDNF levels, but also significantly induced TrkB protein levels reverting MG negative effect on this receptor.

SF totally reverts the reduction of glucose uptake caused by MG exposure. SF can be defined as a multitarget agent modulating different cellular functions leading to a pro-survival frame of particular importance in the prevention / counteraction of multifactorial neurodegenerative diseases.”


A 2020 review Non-enzymatic covalent modifications: a new link between metabolism and epigenetics investigated glycation:

“Non-enzymatic covalent modifications (NECMs) by chemically reactive metabolites have been reported to manipulate chromatin architecture and gene transcription. Unlike canonical post-translational modifications (PTMs), NECMs accumulate over time and are much more dependent on the cellular microenvironment.

A. Guanine residues in DNA and RNA can undergo methylglyoxal glycation, thereby inducing DNA and RNA damage. This DNA damage has few corresponding repair pathways.

B. Histones are primary glycation substrates because of their long half-lives and abundant lysine and arginine residues. Histone glycation was found to induce epigenetic dysregulation through three distinct mechanisms:

  1. Competition with essential enzymatic PTMs for sites (e.g., glycation adducts replace H3K4me3 and H3R8me2);
  2. Changing the charge states of histone tails and subsequently affecting the compaction state of the fiber; and
  3. Altering three-dimensional chromatin architecture by inducing both histone-histone and histone-DNA crosslinking.

Epigenetic impacts of histone glycation were shown to be dependent on sugar concentration and exposure time. Histone and DNA glycation may lead to long term epigenetic impacts on immune responses.

C. Glycation of multiple lysine residues of NRF2 inhibits its oncogenic function. Sugar molecules can influence epigenetic events through glycation of transcription factors and/or their associated regulatory proteins.”

The Transcription factor glycation section referenced a 2011 paper Regulation of the Keap1/Nrf2 system by chemopreventive sulforaphane: implications of posttranslational modifications:

“Nrf2 mRNA level is unaffected by treatment with sulforaphane, suggesting that cellular expression of Nrf2 protein is posttranscriptionally regulated. Posttranslational modifications of Keap1 and Nrf2 proteins seem to play an important role in the regulation of ARE‐dependent gene expression.”


Other curated AGEs papers include:

Broccoli sprout synergies

I was asked for examples of broccoli sprout synergies with supplements mentioned in Week 19 of Changing to a youthful phenotype with broccoli sprouts. I take them together an hour or two before meals to keep meal contents from lowering sulforaphane bioavailability. Sulforaphane peaks in plasma between 1 and 2 hours after ingestion.

sulforaphane peak plasma

I started splitting broccoli sprout doses after reading the first study of A pair of broccoli sprout studies. The second study was Untargeted metabolomic screen reveals changes in human plasma metabolite profiles following consumption of fresh broccoli sprouts.

Those subjects ate only “a single dose of fresh broccoli sprouts (providing 200 μmol SFN equivalents) at 8 AM on study day 1.” A 200 μmol amount of sulforaphane is a 35 mg weight.

For comparison, my daily consumption is a worst-case 52 mg sulforaphane from microwaving 131 g of 3-day-old broccoli sprouts per Estimating daily consumption of broccoli sprout compounds. Every day for 22 weeks now. 🙂

The second study’s measurements through 48 hours produced this informative graphic and text:

“Of the features we identified using metabolite databases and classified as endogenous, eleven were significantly altered.

  • Glutathione (GSH) – a major intracellular antioxidant that conjugates with SFN during metabolism – was significantly decreased in plasma at 6, 12 and 24 hours following sprout intake.
  • GSH precursors glutamine (3 and 24 hours) and cysteine (12 and 24 hours) also decreased.
  • We observed significant decreases in dehydroepiandrosterone (DHEA) at 3, 6 and 12 hours.
  • Decreases in fatty acids reported here suggest that even a single dose of broccoli sprouts may alter plasma lipids in healthy adult populations.

While this study focuses largely on potential effects of SFN, broccoli sprouts contain many other bioactive components (e.g., indoles) that could be responsible for our observations as well as additional health benefits.”

Supplements I take twice daily with broccoli sprouts:

  • 1 gram L-glutamine for replenishment and other purposes;
  • 25 mg DHEA to replenish and other effects;
  • 15 mg then 50 mg zinc, which has a role in GSH metabolism;
  • 500 mg glucosamine (anti-inflammatory, crosstalk with Nrf2 signaling pathway);
  • 500 mg acetyl-L-carnitine (induces Nrf2-dependent mitochondrial biogenesis); and
  • 1400 IU then 2000 IU Vitamin D. A major portion of its effects is Nrf2 activation, like sulforaphane. A virtuous circle develops when taken with broccoli sprouts in that the Vitamin D receptor is a Nrf2 target gene inducible by sulforaphane, which then upregulates Nrf2 expression levels.

One of the things eating Boring Chicken Vegetable Soup twice a day does is replenish cysteine. I eat that and steel-cut oats (another cysteine source) separately from broccoli sprouts.

I take 1 gram flax oil with breakfast and dinner instead of with broccoli sprouts. Haven’t found relevant research on whether broccoli sprout compounds decrease omega-3 polyunsaturated alpha linolenic acid C18:3 as they do these six endogenous fatty acids.


Both studies investigated effects of fresh broccoli sprouts. Timing of their measured decreases and increases are different for me because I microwave broccoli sprouts up to but not exceeding 60°C (140°F).

A section of Microwave broccoli seeds to create sulforaphane highlighted metabolic differences among fresh broccoli sprouts, microwaved broccoli sprouts, and broccoli sprout supplements.

“A metabolic profile resulting from my current practices is probably between the Sprout and BSE (broccoli sprout extract) divided-dose statistics:

  1. Sulforaphane intake is greater than eating raw broccoli sprouts because microwaving 3-day-old broccoli sprouts creates an increased amount of sulforaphane in them before eating.
  2. Sulforaphane uptake from microwaved broccoli sprouts is quicker than eating raw broccoli sprouts. It may not be as immediate as taking sulforaphane supplements, which are usually powders.
  3. Sulforaphane dose from microwaved broccoli sprouts is less dependent on an individual’s metabolism than eating raw broccoli sprouts.
  4. Sulforaphane release from microwaved broccoli sprouts continues on to the gut as does eating raw broccoli sprouts. Sulforaphane release from supplements typically ends in the stomach.”

One thing I didn’t mention in that blog post was that glucoraphanin also increased by microwaving per Microwave broccoli to increase sulforaphane levels. A coauthor clarified a chart’s 60°C (140°F) glucoraphanin amount increased by 27% (2.78 / 2.18 μmol).

Metabolism of broccoli sprout glucoraphanin and other glucosinolates that aren’t preferentially hydrolyzed by microwaving and thorough chewing is assisted in the gut twice a day by:

  • 6 billion IU acidophilus; and
  • 750 mg fructo-oligosaccharides.

Take responsibility for your one precious life – Trained immunity

This 2020 review subject was the normal progression of our immune systems:

“Age-related alterations in the immune system result in high susceptibility to infections, increased risk of hospitalization and mortality. Defects in adaptive immunity underlie the markedly low vaccine efficiency in the elderly. Despite reduced cellular functions, a systemic increase in inflammatory markers, so-called inflammaging, is observed in aged individuals.

Trained immunity is a newly emerging concept that showed that innate immune cells possess non-specific immunological memory established through epigenetic and metabolic reprogramming upon encountering certain pathogenic stimuli.

Novel approaches targeting innate immunity to improve host responses are crucial to evade the consequences of the aged immune system. It is an emerging concept that innate immune cells can manifest memory-like properties that are not antigen-specific and exhibit enhanced responsiveness upon later challenges with heterologous stimuli. Whether trained immune responses change as people age is yet to be explored.”

https://academic.oup.com/intimm/advance-article/doi/10.1093/intimm/dxaa052/5885077 “Overcoming immune dysfunction in the elderly: trained immunity as a novel approach”


Previous papers by this review’s corresponding coauthor were curated in:

There’s no reason to rely entirely on the review’s elaborate vaccination schemes to develop trained immunity. Take responsibility for your one precious life and Train your immune system every day!

Eat broccoli sprouts for your hair!

This 2017 review explored broccoli sprout compounds effects on head hair:

“Skin appendages, notably hair follicles (HFs), can be exposed to high levels of reactive oxygen species (ROS), which are generated through metabolic reactions occurring mostly in the mitochondria, peroxisomes and the endoplasmic reticulum as well as in the plasma membrane. Despite their involvement in redox stress and cellular damage, ROS also have key roles in physiological signalling processes, including but not limited to, control of stem cell quiescence / differentiation, regulation of innate and adaptive immune responses and importantly, normal HF development.

HFs are composed of a series of concentric keratinocyte layers with a central hair shaft, all of which are encapsulated by a mesenchymal connective tissue sheath. Within this structure is an area known as the ‘bulge’, housing a population of epithelial and melanocyte stem cells. The hair bulb, the lowermost portion of the HF, contains transient amplifying cells that produce the rapidly proliferating matrix keratinocytes that give rise to the various cell types of the inner root sheath and hair shaft itself.

Putative impact of NRF2 activation on protection against hair disorders:

  1. Accumulation of excess ROS within crucial HF compartments (i.e. bulb and bulge) can be induced by endogenous and exogenous stressors associated with androgenetic alopecia (AGA), alopecia areata (excessive mast cell degranulation), chemotherapy, UV exposure and even physiological processes such as melanogenesis.
  2. In the HFSCs [hair follicle stem cells] of the bulge, this can lead to reduced FOXP1 signaling, increased senescence and P21-mediated telogen retention, contributing the hair ageing.
  3. In the hair bulb, negative consequences of excessive ROS can include reduced matrix keratinocyte proliferation and Bcl-2 expression, coupled to increased p53 activity and apoptosis. This redox imbalance may also stimulate the dermal papilla-derived TGF-b1 release associated with AGA.
  4. NRF2 activation via SFN [sulforaphane] can induce the expression of numerous downstream targets, hence suggesting the potential to counteract excessive ROS and associated pathologies, for example via enhanced clearance of reactive species, detoxification, NADPH generation and GSH maintenance.
  5. In addition, NRF2 may down-regulate genes that would negatively impact on proliferation and stimulate apoptosis.
  6. Ultimately, the activation of NRF2 has the potential to protect against HF miniaturization, chemotherapy-induced apoptosis, HFSC aging and hair greying, through maintenance of normal redox homeostasis.

Whereas eumelanin (black) is involved in natural UV protection by reducing generation of free radicals, pheomelanin (red) can trigger generation of ROS. It would certainly be interesting to determine whether NRF2 activity is therefore higher in individuals with red as opposed to black hair, in order to mitigate any negative impact from higher ROS generation.

Modulation of NRF2 activity is an attractive approach for further study in the prevention of hair greying and HFSC ageing. The remarkable prospect for NRF2 activators in modulating other oxidative stress-linked disease states, strongly advocates for the development of NRF2 targeting as a novel strategy in modulating redox-associated disorders of the HF.”

https://onlinelibrary.wiley.com/doi/abs/10.1002/bies.201700029 “Oxidative stress management in the hair follicle: Could targeting NRF2 counter age‐related hair disorders and beyond?” (not freely available)


This review was cited in a 2020 Exploring the possibility of predicting human head hair greying from DNA using whole-exome and targeted NGS data:

“This study aimed to assess the potential of genetic data to predict hair greying in a population of nearly 1000 individuals from Poland. Most of the prediction information was brought by age alone. Genetic variants explained < 10% of hair greying variation and the impact of particular SNPs on prediction accuracy was found to be small.

Study population included 673 males (67.4%) and 325 (32.6%) females. The mean age of the participants was 30.5 ± 8.8.

Hair greying was recorded in 14.3% of individuals aged 18–30 and the prevalence of grey hair was noted to be significantly higher in young males when comparing to young females (17.8 and 9.2%, respectively). The incidence of grey hair increased to 29.5% in the group of people aged 18–40 years and was 84.2% when people aged ≥40 years were considered.

Because pleiotropy is so common, it would be impossible to predict natural phenotypes avoiding genes involved in determination of pathological phenotypes. The penetrance of individual SNP variants is usually low and they altogether can only explain a small fraction of the predisposition to the disease.

Prediction of hair greying status solely based on genetic information is currently impossible.”


A 2020 review had a pertinent evaluation scheme:

“Geroprotectors are pharmacological agents that decrease the rate of aging and extend lifespan. We proposed a set of primary and secondary selection criteria for potential geroprotectors. Primary criteria:

  1. The life extension in experiments with wild type animal models. The geroprotector should prolong the life of the model beyond the intact maximum lifespan, protecting it from one or more mechanisms of aging.
  2. Improvement of molecular, cellular, and physiological biomarkers to a younger state or slow down the progression of age-related changes in humans.
  3. Most potential geroprotectors are preventive only when applied at relatively high concentrations. The lifespan-extending dose should be several orders of magnitude less than the toxic dose.
  4. Minimal side effects at the therapeutic dosage at chronic application.
  5. The potential benefit of taking a geroprotector may come after a long period. Potential geroprotectors should initially improve some parameters of health-related quality of life: physical, mental, emotional, or social functioning of the person.”

https://www.mdpi.com/2076-3921/9/6/529/htm “Terpenoids as Potential Geroprotectors”


IMG_20200822_064852

Aging as a normal disease

This 2018 review explained:

“Aging is the sum of all age-related diseases. Aging and its diseases are inseparable, as these diseases are manifestations of aging.

An aged appearance (e.g., grey hair, wrinkles, cushingoid body types and loss of muscles) are manifestations of pre-diseases. For example, an aged appearance may reflect hypercortisolism, sarcopenia, osteoporosis, skin pre-diseases.

Instead of healthy aging, we could use the terms pre-disease aging or decelerated aging. Treatments are generally more effective at pre-disease stages, associated with hyper-function, than at disease stages, associated with functional decline.

The decision to treat or not to treat is often determined by whether it is possible to treat.

A treatment that slows aging increases both healthspan (subclinical period) and lifespan, whereas a treatment that increases lifespan (e.g., coronary bypass, defibrillation) is not necessarily increase healthspan. The goal of both anti-aging therapies and preventive medicine is to extend healthspan (by preventing diseases), thus extending total lifespan.

The fact that aging is an obligatory part of the life of all organisms is not important. Aging can be treated as a pre-disease to prevent its progression to diseases. Aging does not need to be defined as a disease to be treated.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286826/ “Disease or not, aging is easily treatable”




Grow a broccoli sprouts Victory Garden today!

By request, here’s what I recommend after growing and eating broccoli sprouts every day for the past twenty weeks.

1. Develop a strategic goal. Eating broccoli sprouts can achieve several goals. Mine has been to address inflammation.

2. Use a relevant model. I used the 2018 clinical trial Effects of long-term consumption of broccoli sprouts on inflammatory markers in overweight subjects. For ten weeks the trial’s subjects daily ate 30 grams of fresh super sprouts that were at least a week old.

3. Develop tactical goals. I initially adopted a goal of 60 grams of regular sprouts started with one tablespoon of broccoli seeds. I follow 3-day-old broccoli sprouts have the optimal yields and Microwave broccoli to increase sulforaphane levels guidelines. A major difference from the model is that I create broccoli sprout hydrolysis compounds just before eating 3-day-old broccoli sprouts by microwaving them.

4. Obtain materials and equipment. Assuming you have a microwave, items that may not already be in your kitchen:

  • Broccoli seeds. A 2.5 lb package may last seven weeks using two tablespoons a day. Vendors of broccoli seeds intended for home sprouting don’t differentiate their products with study evidence, so get what’s affordable.
  • A fine mesh strainer. I use an 8-inch diameter one that isn’t long for this world because it has a lip that catches seeds, coats, and sprouts.
  • Filtered water.
  • A thermometer that can measure up to 60°C (140°F).
  • Seven bowls that hold at least 16 fluid ounces. If your Victory Garden will be one-tablespoon batches started twice a day, it will look something like this, with the seventh bowl in the dishwasher:

5. Adopt methods. If you acknowledge that something you did or didn’t do is probably the cause of variability, you can make improvements.

  • I use a 12-6-6 schedule to rinse broccoli sprouts three times a day. It produces better results than a 12-12 twice daily rinse schedule.
  • I shape batches with a teaspoon so that all sprouts touch.
  • The teaspoon and strainer are rinsed in between straining batches to prevent potential problems in one batch from spreading to others. They are also cleaned in the dishwasher every day.
  • Every a.m. and p.m. I take the five oldest batches off my pantry shelf, and soak them for five minutes.
  • While those five batches are soaking, I start a new batch by soaking one tablespoon of broccoli seeds. The 12-hour-old batch is strained, rinsed, strained again, then both bowls put on my pantry shelf.
  • I strain the five soaking batches, put the four younger ones on the shelf, and close the pantry door.
  • I reimmerse the 3-day-old broccoli sprouts batch in 100 ml filtered water, then microwave it on 1000W full power for 35 seconds to achieve up to but not exceeding 60°C (140°F).
  • I strain the microwaved broccoli sprouts, and wait five minutes to allow further myrosinase hydrolization of glucoraphanin and other glucosinolates into sulforaphane and other healthy compounds.
  • I mix in homemade unsalted sauerkraut when I eat microwaved broccoli sprouts. It helps ensure that I thoroughly chew sprouts. Whatever glucosinolate hydrolization hadn’t already taken place will be initiated by chewing.
  • About six hours between starting new a.m. and p.m. batches, I soak the five oldest batches for five minutes, strain them, and put them back on the shelf.

6. Adapt tactics to achieve goals. I didn’t get expected results after five weeks of eating broccoli sprouts started from one tablespoon of seeds, so I doubled the daily starting amount to two tablespoons. I split starting amounts of seeds into a.m. and p.m. one-tablespoon portions after reading A pair of broccoli sprout studies. I don’t eat sprouts immediately before, during, or after meals per Bioavailability of Isothiocyanates From Broccoli Sprouts in Protein, Lipid, and Fiber Gels which found that eating protein, fats, and fiber along with broccoli sprouts lowered compounds’ bioavailability.

7. Never give up. Growing a Victory Garden is a way to take responsibility for your one precious life. The primary enemy of such efforts is Madness of Crowds behavioral contagion. If you can keep that from infecting you, you can look forward to transformational experiences like I had during Week 9.

8. Take a walk every day.

Sleep

If you can stand the woo of two Californians trying to outwoo each other, listen to these five podcasts with a sleep scientist.

https://peterattiamd.com/matthewwalker1/

“Ambien, sedation, hypnotives, are not sleep.

Sleep is a life support system. It’s the Swiss army knife of health.

Lack of sleep is like a broken water pipe in your home that leaks down into every nook and cranny of your physiology.

Sleep research is not being transmitted to clinical practice.”


I live on the US East Coast. Hyperbole in normal conversations outside of urban centers is an exception.

It’s different on the West Coast. For example:

  • Interviewer assertions regarding heart rate variability should be compared and contrasted with Dead physiological science zombified by psychological research evidence that:

    “A broad base of further evidence was amassed within human cardiac, circulatory, and autonomic physiology such that the hypotheses do not work as described.”

  • Interviewer favorable comments for MDMA (Ecstasy) “to deal with issues of underlying trauma, anxiety, and depression.”

Week 20 of Changing to a youthful phenotype with broccoli sprouts

Following up Week 19:

1. I went overboard this week with broccoli sprout measurements. Rinsing broccoli sprouts on a 12-6-6 schedule, each day’s WET and DRY a.m. weights were usually less than p.m. weights. But were they significant weight differences?

  1. Having no moisture for 12 hours vs. 6 hours produced a significant difference in DRY a.m. vs. p.m. weights (A).
  2. Moisture was the equalizer, though, as WET a.m. vs. p.m. weights weren’t significantly different (B).
  3. (C) Were a.m. WET weight gain percentages the same as p.m.? No.
  4. Although most of Week 19’s measurements were taken on an 8-8-8 schedule, its 65.5 ± 4.4 g WET average was confirmed by both 61.8 ± 6.2 g a.m. and 66.4 ± 4.7 g p.m. distributions.

I’ll guess that a laboratory with automatic rinsing every 6 hours would change differences in DRY a.m. vs. p.m. weights (A) and WET weight gain percentages (C) to become insignificant. Removing human causes of variability would improve results.

2. Per Week 19’s item 2, eating protein, fats, and fiber along with broccoli sprouts lowered compounds’ bioavailability. I’m looking for accompaniments that won’t have adverse effects.

Eating 60+ grams of broccoli sprouts twice a day is a lot. Mixing in sauerkraut tastes alright, but commercial brands have too much sodium.

3. It’s been 11 weeks since I posted A claim of improved cognitive function. I made many such connections after a transformational Week 9.

I had no idea that would happen. And I won’t come down no more.

4. Tomorrow will be Day 140 of eating broccoli sprouts every day. I’ve successfully addressed inflammation, and will maintain current practices.

Left ankle and knee twinges are among reminders of other aging phenotype aspects. The body clock reset described in An environmental signaling paradigm of aging apparently requires more than what I’ve been doing.

Eat broccoli sprouts for your skin!

This 2020 Swiss review subject was the interaction of Nrf2 activators and skin:

“The electrophile and Nrf2 activator dimethyl fumarate (DMF) is an established and efficient drug for patients suffering from the common inflammatory skin disease psoriasis. DMF is being tested for pharmacological activity in several other inflammatory skin conditions.

dmf

Psoriasis is a chronic inflammatory skin disease affecting 2–4% of the population and plaque psoriasis is the most common type, affecting about 90% of all patients. As about 30% of all patients suffer from moderate and severe psoriasis, there is a strong need for efficient systemic treatment options with few side effects.

SFN [sulforaphane] blocks NF-κB activity by several mechanisms. SFN oxidizes IκB, thereby inhibiting its phosphorylation and downstream NF-κB activation, but also targets specific cysteine residues of p50/p65, causing a reduction in DNA binding.

More indirect effects have also been suggested. SFN induces HO-1 expression via Nrf2, which in turn inhibits NF-κB. The isothiocyanate can also react with and oxidize components of cellular redox buffers, such as glutathione and thioredoxin, which are required to retain NF-κB’s DNA-binding capacity.

NLRP3 is believed to be critically involved in common diseases, whereas its role in immunity is rather minor. The mechanisms underlying NLRP3 inflammasome activation are of high medical interest.

Electrophiles can directly inhibit inflammasome activation. SFN inhibits activation of NLRP3 in the absence of NRF2 expression in a very fast manner, suggesting that transcriptional effects are not relevant for NLRP3 inhibition. SFN inhibits NLRP3 even in KEAP1 knockout cells.

All these results demonstrate that electrophiles can inhibit the inflammasome pathway in a direct manner, perhaps via the modification of reactive cysteine residues of inflammasome proteins or those which regulate activation of these complexes.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072181/ “Electrophiles against (Skin) Diseases: More Than Nrf2”


These reviewers focused on a pharmaceutical. Read this article for progress made on a generic:

“Biogen is expected to appeal this ruling against its Tecfidera patent protection, which is not due to expire until 2028. Its list price is reported to be about $2,026 for a two-week (14 day) supply at 120 mg.

‘The District Court decision clears the legal pathway for us to bring our dimethyl fumarate product to market, and we are working with the FDA to accelerate our regulatory approval target action date, which currently is November 16.'”


Broccoli or Sulforaphane: Is It the Source or Dose That Matters? listed 15 mouse studies and 4 human studies of sulforaphane treatments of skin diseases in Supplementary Material Table S3.

From Novel Nrf2 activators from microbial transformation products inhibit blood–retinal barrier permeability in rabbits:

“The cysteine residue of sulforaphane works as a weak electrophile and it interacts with cysteine residues of Keap1. Dimethyl fumarate is also a weak electrophile.

Nrf2 activity was evaluated by NQO1 induction activity in Hepa1c1c7 cells. RS9 was the most potent and the concentration needed to double (CD) the specific Nrf2 activity was 0.2 nM. The CD values for bardoxolone methyl, sulforaphane and dimethyl fumarate were 0.9 nM, 154.4 nM and 13.3 μM respectively.”


1. This review didn’t mention dimethyl fumarate’s NQO1 induction CD value because..? It’s one of Nrf2 signaling pathway’s main studied parameters along with HO-1. For example, from Autism biomarkers and sulforaphane:

“This time point was chosen based on our earlier observations of the kinetics of upregulation of Nrf2-dependent genes by SF, and was expected to capture the increased mRNA production of both very fast (HO-1) and relatively slow (NQO1) responders.”

2. What about adverse effects? From Sulforaphane and RNAs:

“DMF 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.”

3. What about prevention mechanisms for skin problems? Skin care isn’t just cancer prevention.


So, what can a person do to treat an inflammation problem in our largest organ – skin?

  • Pay $2,026 every two weeks to take a daily 120 mg dose of a brand name pharmaceutical?
  • Wait around for some hypothetical future “development of new tailor-made molecules and drugs for the many inflammatory conditions which are associated with Nrf2, NF-κB and inflammasomes”?
  • Try other treatments that just address symptoms, not causes?

Or eat daily clinically-relevant broccoli sprout dosages for < $500 a year?