Immune system

Eat broccoli sprouts to maintain your cells

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

Two more papers cited Precondition your defenses with broccoli sprouts, starting with a 2024 review of broccoli compounds’ influences on autophagy and cellular function:

“Promotion of autophagy has been related to lifespan expansion, tumor suppression, and maintenance of metabolic health. Alterations in this pathway have been related to human diseases or pathological states including neurodegenerative diseases, stroke, metabolic alterations, or cancer.

We describe the different types of glucosinolates (GSL), grouped depending on the structure of their side chain, with special attention to those GSL and their derived isothiocyanate (ITC) which have been suggested to be of relevance to treat or prevent human diseases, their structure, and plant source.

gsl-itc

It has been shown that SFN activates TFEB, boosting expression of genes required for autophagosome and lysosome biogenesis. SFN induced a short burst of ROS necessary for TFEB activation, and TFEB activity was required for SFN-induced NRF2 activation and protection against acute and chronic oxidative stress.

TFEB was also required for SFN-induced removal of excessive mitochondrial ROS, indicating an important role for mitophagy in SFN-induced antioxidant response. Thus, direct activation of NRF2 by SFN or other ITC can promote autophagy.

Research on autophagy has been characterized by controversies regarding autophagy mediating survival or cell death, or its role in health and disease, not only because autophagy is a complicated process with context dependent roles depending on the cell type or the step of the autophagic pathway being modulated, but also, because in occasions, autophagy is not measured correctly.

An interesting area of research would be to decipher effects of NRF2-regulated or NRF2-independent autophagy induction by ITC, and whether these effects would determine the role of the autophagic process in cellular survival or death. Also, it is needed to clarify which of the effects regulated by ITC are mediated by autophagy, and which ones are not, and the importance of autophagy induction in the therapeutic effects mediated by ITC.”

https://link.springer.com/article/10.1007/s11101-024-09944-w “Glucosinolates, isothiocyanates, and their role in the regulation of autophagy and cellular function” (not freely available)

This paper’s contact coauthor (who provided access to the full paper) is also the contact for Our model clinical trial for Changing to a youthful phenotype with broccoli sprouts.

The coauthors of Exercise substitutes? published a 2024 human cell study:

“While physical activity is an excellent inducer of mitochondrial turnover, its ability to ubiquitously activate and enhance mitochondrial turnover prevents definitive differentiation of the contribution made by each pathway. We employed three agents which are activators of important biological markers involved in antioxidant signaling, mitochondrial autophagy, and mitochondrial biogenesis.

Results suggest that early time points of treatment increase upstream pathway activity, whereas later time points represent increased phenotypic expression of related downstream markers. Findings suggest that spatiotemporal progression of these mechanisms following drug treatment is another important factor to consider when examining subcellular changes towards mitochondrial turnover in muscle.”

https://www.sciencedirect.com/science/article/pii/S2666337624000398 “Sulforaphane, Urolithin A, and ZLN005 induce time-dependent alterations in antioxidant capacity, mitophagy, and mitochondrial biogenesis in muscle cells”

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Year Four of Changing to a youthful phenotype with sprouts

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

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

Foods are the same as Week 189 except I eat two raw eggs in the morning after Avena sativa oat sprouts. Supplements are the same except I stopped the ProdromeGlia plasmalogen precursor supplement due to it being out-of-stock.

It’s annoying because after a few days, my sense of smell and taste improvements reverted without ProdromeGlia. I’ve continued ProdromeNeuro, but it seems that its combination with ProdromeGlia was essential for stopping my left ulnar nerve elbow pain, which returned after a week without ProdromeGlia.

2. You may have noticed that earlier this month, a U.S. government agency was forced by a lawsuit to delete their 2021 propaganda pieces against a medication that’s safer than acetaminophen. I had a prescription that local pharmacies suddenly wouldn’t fill in August 2021.

Plenty of workarounds have been available, though. I hadn’t mentioned it before, but a prophylactic weekly intake may have played a part in me not being sick even one day this decade.

Another part was that my living and working in the Washington DC area for 30+ years through 2017 taught me, as an initial response, to not believe a single word of what a government employee said. I’ve since extended that to many other types of compromised people, such as medical professionals.

3. Our ancestors evolved to deal with everyday bacteria, viruses, and other pathogens. Train your immune system every day! disclosed that I was in Milan, Italy on the same February 22-23, 2020 weekend that ten towns were closed south of Milan. I still haven’t experienced any symptoms.

  • One factor in immune response was that fifteen years previous, I’d taken daily steps with yeast cell wall β-glucan to guard against the phenotypical immune system collapse of old age.
  • Another factor was that I’d ridden the filthy Washington DC Metro twice a day to-and-from work for years, and had already been exposed to who knows what.

Treat your gut microbiota well. Give them what they want – including cruciferous sprouts – and expect reciprocity.

what

Ergothioneine dosing, Part 2

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

Continuing Part 1 with a 2024 rodent healthspan and lifespan study:

“We investigated the effects of daily oral supplementation of ergothioneine (ERGO) dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice.

11357_2024_1111_Fig1_HTML

The ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age. This was compatible with dramatic suppression by ERGO of age-related increments in plasma biomarkers. ERGO also rescued age-related impairments in learning and memory ability.

Ingestion of ERGO may promote longevity and healthy aging in male mice, possibly through multiple biological mechanisms.”

https://link.springer.com/article/10.1007/s11357-024-01111-5 “Ergothioneine promotes longevity and healthy aging in male mice”

Subjects’ plasma ergothioneine levels of an estimated 4 ~ 5 mg/kg daily dose were:

11357_2024_1111_Fig3_HTML

A human equivalent daily dose is an estimated 22 mg to 28 mg (4 or 5 mg x .081 x 70 kg).

The third paper in Part 1 cited a 2017 clinical trial that provided 5 mg and 25 mg ergothioneine doses for 7 days, resulting in these plasma ergothioneine levels:

figure 3

The first paper of Part 1 referenced a 2020 human study where the dose was 5 mg/day for 12 weeks, but I don’t have access to it. It’s unclear whether humans could continually raise ergothioneine levels by daily consumption throughout our lives as did this rodent study.

A 2024 paper reviewed the importance of ergothioneine to humans:

“We propose that the diet-derived compound ergothioneine (ET) is an important nutrient in the human body, especially for maintenance of normal brain function, and that low body ET levels predispose humans to significantly increased risks of neurodegenerative and possibly other age-related diseases.

Work by multiple groups has established that low ET levels in humans are associated not only with cognitive impairment/AD but also with other age-related conditions, including frailty, Parkinson’s disease, vascular dementia, chronic renal disease, cardiovascular disease, and macular degeneration. Low ET levels also correlate with increased risk of developing preeclampsia in pregnant women [53].

Plasma ET levels from healthy (age-matched) vs unhealthy individuals in Singapore – Mild cognitive impairment (MCI); Alzheimer’s disease (AD); vascular dementia (VaD); Parkinson’s disease (PD); age-related macular degeneration (AMD):

1-s2.0-S0891584924001357-gr2_lrg

  • Does low ET cause or contribute to age-related neurodegeneration, or
  • Does disease cause low ET, or
  • Low ET and increased disease risk are both caused by something else, as yet unidentified?

Prevention of neurodegeneration is especially important, since by the time dementia is usually diagnosed damage to the brain is extensive and likely irreversible.”

https://www.sciencedirect.com/science/article/pii/S0891584924001357 “Are age-related neurodegenerative diseases caused by a lack of the diet-derived compound ergothioneine?”

Whether or not the healthy individuals ate mushrooms daily in the above graphic was lost while conglomerating multiple studies.

Note that scales of the above two human graphics are a thousand times smaller than the above rodent graphic. I thought that maybe the rodent study made a plasma ergothioneine calculation error, but didn’t see one in the provided Supplementary data.

Reference 53 of the second paper is a 2023 human study:

“We analysed early pregnancy samples from a cohort of 432 first time mothers. Of these 432 women, 97 went on to develop pre-term or term pre-eclampsia (PE).

If a threshold was set at the 90th percentile of the reference range in the control population (≥462 ng/ml), only one of these 97 women (1%) developed PE, versus 96/397 (24.2%) whose ergothioneine level was below this threshold. One possible interpretation of these findings, consistent with previous experiments in a reduced uterine perfusion model in rats, is that ergothioneine may indeed prove protective against PE in humans.”

https://portlandpress.com/bioscirep/article/43/7/BSR20230160/233119/Relationship-between-the-concentration-of “Relationship between the concentration of ergothioneine in plasma and the likelihood of developing pre-eclampsia”

Eyeballing the Healthy individuals in the above graphic, none of those 544 people were below this study’s 462 ng threshold.

A 2023 companion article analyzed the third paper’s unusual findings:

“These results suggest that there might be a dichotomized association between ergothioneine concentrations and preeclampsia; and only a high ergothioneine level over 90th percentile of the control population could be protective against preeclampsia.

Univariable results showed that ergothioneine had a significant non-linear association with preeclampsia and it would start to offer protective effect from 300 ng/ml onward. Analysis also confirmed that body mass index was significantly associated with an increased risk of preeclampsia.

A large observational study could strengthen the causal association between ergothioneine and preeclampsia. If confirmed, a randomized controlled trial (RCT) assessing whether ergothioneine supplementation can reduce risk of preeclampsia will be imminently feasible. Ideally, such RCT should compare placebo with a range of different doses of ergothioneine to identify the best or minimal effective dose, given its good safety records, including in pregnancy, with a no-observed-adverse-effect level (NOAEL) of 800 mg/kg body weight per day.”

https://portlandpress.com/bioscirep/article/43/8/BSR20231076/233395/Dose-related-relationship-between-ergothioneine “Dose-related relationship between ergothioneine concentrations and risk of preeclampsia”

My daily mushroom ergothioneine dose is around 7 mg, and I weigh about 70 kg. I don’t think a daily 800 mg/kg ergothioneine dose would be desirable for anybody, regardless of what experts say.

How many times have public health employees been wrong this decade? Would you bet your or your child’s health on their advice?

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Sulforaphane’s effects on autism and liver disease

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

Here are two more papers that cited Precondition your defenses with broccoli sprouts, starting with a 2024 human / rodent study investigating gut microbiota / sulforaphane’s effects on autism:

“Sulforaphane (SFN) has been found to alleviate complications linked with several diseases by regulating gut microbiota (GM), while the effect of GM on SFN for autism spectrum disorders (ASD) has not been studied. We evaluated therapeutic effects of SFN on maternal immune activation (MIA)-induced ASD-like rat model and pediatric autism patients aged 4–7 years.

OSU-SO for social interactive OSU behavioral subscores, OSU-CO for non-verbal communicative OSU behavioral [significant] subscores, and OSU-ST for repetitive or ritualistic OSU behavioral subscores:

fnut-10-1294057-g0005

Although gut microbiota composition was significantly altered in SFN-treated ASD-like rats, alteration of GM was not evident in ASD patients after 12 weeks of SFN treatment. Limitations in this study:

  1. Studies were conducted in male rats and boys only;
  2. The sample size of our clinical study is relatively small [6 SFN-treated boys] and needs to be further expanded in the future; and
  3. This study only uncovered a potential link between gut flora and the therapeutic effects of SFN on ASD.

SFN treatment alleviates social deficits in MIA-induced ASD-like rats and ASD patients, and improvements might be associated with gut microbiota.”

https://www.frontiersin.org/articles/10.3389/fnut.2023.1294057/full “Therapeutic efficacy of sulforaphane in autism spectrum disorders and its association with gut microbiota: animal model and human longitudinal studies”

The 2022 Efficacy of Sulforaphane in Treatment of Children with Autism Spectrum Disorder: A Randomized Double-Blind Placebo-Controlled Multi-center Trial (not freely available) was referenced for sulforaphane (actually, glucoraphanin with myrosinase enzyme) doses:

“Dosing was weight-based:

  • Two tablets/day for 10–29 lb;
  • Three tablets/day for 30–49 lb;
  • Four tablets/day for 50–69 lb.

An estimated delivery of approximately 24, 36, and 48 μmol of sulforaphane daily was expected in the respective SF dosage groups.”

Weights of the above μmol estimated dose amounts per https://pubchem.ncbi.nlm.nih.gov/compound/sulforaphane are 4.3, 6.4, and 8.5 mg, respectively. An average weight of a 4-year-old boy is 36 lbs / 16.3 kg, and a 7-year-old boy is 51.1 lbs / 23.2 kg.

This study’s maternal immune activation was done by injecting lipopolysaccharide into pregnant rats. Would injecting pregnant women with immune-activating substances have similar harmful effects on the fetus? We don’t have evidence because unbiased and unconflicted studies looking for such effects weren’t sponsored and/or published before immune-activating substances’ deployments.

A 2024 rodent study investigated sulforaphane’s effects on diabetic liver damage:

“We investigated whether sulforaphane, an Nrf2 activator and antioxidant, prevents diabetes-induced hepatic ferroptosis, and the mechanisms involved. Results showed that diabetes-induced inactivation of Nrf2 and decreased expression of its downstream antiferroptotic molecules critical for:

  • Antioxidative defense (catalase, superoxide dismutases, thioredoxin reductase);
  • Iron metabolism (ferritin heavy chain (FTH1), ferroportin 1);
  • Glutathione (GSH) synthesis (cystine-glutamate antiporter system, cystathionase, glutamate-cysteine ligase catalitic subunit, glutamate-cysteine ligase modifier subunit, glutathione synthetase); and
  • GSH recycling – glutathione reductase (GR)

were reversed/increased by sulforaphane treatment.

Diabetes-induced increases in serum glucose and triglyceride levels were also significantly reduced by sulforaphane. Taken together, our results demonstrate a potent effect of SFN in inhibiting ferroptotic death of hepatocytes under diabetic conditions in vivo, thereby alleviating liver injury.

This is the first study to demonstrate the protective role of SFN against ferroptosis in the liver of diabetic mice. This nominates sulforaphane as a promising phytopharmaceutical for the prevention/alleviation of ferroptosis in diabetes-related pathologies.”

https://iubmb.onlinelibrary.wiley.com/doi/10.1002/biof.2042 “Sulforaphane prevents diabetes-induced hepatic ferroptosis by activating Nrf2 signaling axis”

Improving peroxisomal function

gettingwell4 4-5 stars Advanced knowledge, Brain development, Brainstem, Cerebellum, Cerebrum, Epigenetics, Immune system, Lower brain, Memory, Stress , , , ,

A 2024 review provided details about “mysteries” in peroxisome research:

“Peroxisomes are key metabolic organelles with essential functions in cellular lipid metabolism (e.g., β-oxidation of fatty acids and synthesis of ether phospholipids, which contribute to myelin sheath formation), and metabolism of reactive oxygen species (ROS), particularly hydrogen peroxide. Loss of peroxisomal function causes severe metabolic disorders in humans.

Additional non-metabolic roles of peroxisomes have been revealed in cellular stress responses, regulation of cellular redox balance and healthy ageing, pathogen and antiviral defence, and as cellular signalling platforms. New findings also point to a role in regulation of immune responses.

In our previous reviews, we addressed the role of peroxisomes in the brain, in neurological disorders, in development of cancer, and in antiviral defence. To avoid repetition, we refer to those articles where appropriate, and to more specialised recent reviews on peroxisome biology.

418_2023_2259_Fig5

Proper functioning of peroxisomes in metabolism requires the concerted interaction with other subcellular organelles, including the endoplasmic reticulum (ER), mitochondria, lipid droplets, lysosomes, and the cytosol. A striking example of peroxisome-ER metabolic cooperation is de novo biosynthesis of ether phospholipids.

Metabolic activities of peroxisomes, such as ɑ- and β-oxidation of fatty acids, plasmalogen synthesis, and ROS/reactive nitrogen species metabolism, have been linked to numerous immune-related pathways. Roles for peroxisomes in immune and defence mechanisms have opened a new field of peroxisome research, and highlight once more how important peroxisomes are for human health and disease.

It is still not fully understood how peroxisomal functions and abundance are regulated, what kinases/phosphatases are involved, or how peroxisomes are linked to cellular signalling pathways and how they act as signalling platforms.”

https://link.springer.com/article/10.1007/s00418-023-02259-5 “The peroxisome: an update on mysteries 3.0”

Last Friday was Day 90 of a 90-day trial of plasmalogens coincident with improving peroxisomal function via resistance exercise and time-restricted eating. A sticking point has been leg resistance exercises. Ankle issues are interfering with progress, although beach walks aren’t similarly affected. I’m almost back to an upper body exercise routine of five years ago, and I’ve added a half-dozen abs exercises.

I’ll continue taking the two Prodrome plasmalogen precursor supplements (ProdromeGlia and ProdromeNeuro) and with efforts to improve peroxisomal function. Since achieving effective resistance exercise levels is taking longer than expected, and my crystal ball is out-of-commission, I don’t have a realistic end time estimate for stopping the supplements.

Get a little stress into your life

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

Two reviews on beneficial effects of mild stress, starting with a 2024 paper coauthored by the lead researcher of Sulforaphane in the Goldilocks zone:

“This paper addresses how long lifespan can be extended via multiple interventions, such as dietary supplements, pharmaceutical agents, caloric restriction, intermittent fasting, exercise, and other activities. This evaluation was framed within the context of hormesis, a biphasic dose response with specific quantitative features describing the limits of biological/phenotypic plasticity for integrative biological endpoints.

Human maximum longevity has remained relatively constant in the 110–120 year time period. Yet, research with C. elegans indicates that hormetic processes increase both average (median/mean) and maximum lifespans. These observations were consistently shown by different research teams using highly diverse stressors but with generally similar experimental methods. Thus, lifespan can be increased in an overall average manner but also within the context of the maximum lifespan potential via hormetic processes, which has not been shown to occur in human population studies.

In multiple experimental and epidemiological contexts, antioxidants have prevented lifespan extension of numerous hormetic agents and blocked human health benefits (e.g., exercise), supporting the hypothesis that oxidative stress is necessary for healthspan improvements and lifespan extension.

Maximum lifespan may be prolonged by extending the lifespan of healthy subjects. Median lifespan would be enhanced by protecting those who are susceptible to genetic/environmental diseases.

Most experimental studies indicate that maximum hormetic lifespan benefits are in the 15 – 25% range when responses are optimized. Human-based benefits could be expected to be less than this maximum range. The issue of hormetic synergies is important to consider, but the available data to date indicates that these benefits are also constrained by limits of biological plasticity.”

https://www.sciencedirect.com/science/article/abs/pii/S1568163723003409 “Hormesis determines lifespan” (not freely available) Thanks to Dr. Evgenios Agathokleous for providing a copy.

A 2023 review of nematode studies was cited three times:

“While stress response pathways are important in allowing organisms to survive acute and chronic stresses, these pathways also contribute to longevity under unstressed conditions. Multiple stress response pathways are required for normal lifespan in wild-type worms, and all of the stress response pathways discussed in this review contribute to the longevity of long-lived mutants.

Four stress response pathways were consistently required for longevity:

  1. The FOXO transcription factor DAF-16-mediated stress response;
  2. The Nrf2 homolog SKN-1-mediated oxidative stress response;
  3. The cytoplasmic unfolded protein response (cyto-UPR); and
  4. The endoplasmic reticulum unfolded protein response (ER-UPR)

are required for normal lifespan, and may contribute to the extended lifespan of long-lived mutants. Developing strategies to activate these pathways, at the right time(s) and in the right tissue(s), may help to promote healthy aging and ameliorate age-onset disease.”

https://www.sciencedirect.com/science/article/pii/S1568163723001009 “Biological resilience and aging: Activation of stress response pathways contributes to lifespan extension”

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Eat broccoli sprouts for your liver, Part 2

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

A 2023 review cited Part 1 and caught up other relevant research on sulforaphane effects through early 2023:

“A growing number of studies have reported that sulforaphane (SFN) could significantly ameliorate hepatic steatosis and prevent development of fatty liver, improve insulin sensitivity, attenuate oxidative damage and liver injury, induce apoptosis, and inhibit proliferation of hepatoma cells through multiple signaling pathways.

SFN inhibits lipogenesis and oxidative stress while enhancing lipid droplet degradation through modulating expression of genes involved in lipid synthesis, metabolism, and oxidation. SFN modulates autophagy, lipolysis, mitochondrial function, and ER stress to alleviate fatty liver through AMPK-, AHR-, PGC1α-, and FGF21-mediated pathways.

fphar-14-1256029-g001

There is still a gap between basic research and clinical application of SFN. More efficient delivery systems and precise dose schedules of SFN are expected to be developed in future studies, which would improve its solubility, stability, and bioavailability, and reduce inter-individual variations in humans.”

https://www.frontiersin.org/articles/10.3389/fphar.2023.1256029/full “Therapeutic potential of sulforaphane in liver diseases: a review”

These reviewers did alright gathering papers. That’s only part of what needed to be done, with the other part being reading, understanding, and interpreting these papers.

First example: Sulforaphane in the Goldilocks zone was cited [reference 12], but applicability to this review with its main point “The stimulatory zone for in vitro studies proved to be consistently in the 1-10 μM range” as in Figure 10 “Effects of R-sulforaphane on phase II enzyme activation in precision-cut liver slices of young adult male Albino Wistar rats” wasn’t understood:

figure 10

These reviewers complained:

“Few dose-response studies on SFN have been reported, and the range of its effective doses is unclear. Doses used in most animal studies have exceeded the highest dose of SFN used in humans.”

So it might have taken a little bit more effort, but these reviewers could have highlighted studies where sulforaphane liver treatments were in the 1-10 μM potentially therapeutic range.

Another example: these reviewers said “The half-life of SFN is very short due to its rapid metabolism in the human body.” They missed a point that the second paper in How much sulforaphane is suitable for healthy people? [reference 46] made in section 6.4. “NQO1 Pharmacokinetics following SFN Ingestion:”

“Maximal induction of NQO1 occurred at around 24 hours, declining thereafter (Figure 8). This peak represents an approximate 2.8-fold induction over baseline.

These findings are useful when considering the effect of SFN as an intervention material in acute compared with chronic conditions. A significant increase in NQO1 occurred between 6 and 12 hours, a timeframe that may not be sufficiently responsive for management of an acute state, leaving one to conclude that NQO1 induction is best suited to chronic conditions where a rapid response may not be necessary.”

OMCL2019-2716870.008

Sulforaphane’s effects of inducing NQO1 for its cytoprotective, antioxidant, and other functions lasts for days, regardless of when sulforaphane leaves the bloodstream.

Take acetyl-L-carnitine if you are healthy

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

Eight 2023 acetyl-L-carnitine / L-carnitine papers, starting with three healthy human studies:

“Thirty healthy volunteers aged between 19 and 52 years were divided randomly into two equal groups, one of which received 1000 mg of L-carnitine (LC) per day over a 12-week period. Total cholesterol and HDL-C increased significantly after supplementation. LC could be useful in impeding development of heart diseases in subjects with low HDL-C.”

https://journaljammr.com/index.php/JAMMR/article/view/5166 “L-Carnitine Increases High Density Lipoprotein-Cholesterol in Healthy Individuals: A Randomized Trial”

Rationale for dose selection wasn’t provided, and the possibility of limited results due to poor study design wasn’t mentioned.

“This study examined effects of 12 weeks of LC supplementation on bone mineral density (BMD) and selected blood markers involved in bone metabolism of postmenopausal women participating in a resistance training (RT) program. Participants’ diets were supplemented with either 1 g of LC-L-tartrate and 3 g of leucine per day (LC group) or 4 g of leucine per day as a placebo (PLA group), in a double-blind fashion.

Because the study protocol consisted of both exercise and supplementation, some favorable changes in the BMD could be expected. However, it was not possible to detect them in the short study period. No significant modification in BMDs of the spine, hip, and total skeleton and no differences between groups in one-repetition maximum could be due to the relatively short duration of the RT intervention.”

https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-023-00752-1 “Effect of a 3-month L-carnitine supplementation and resistance training program on circulating markers and bone mineral density in postmenopausal women: a randomized controlled trial”

Same comments as the first study regarding no rationale for dose selection, and no mention that limited results were possibly due to an inadequate dose.

In a letter to the editor, a researcher took issue with a study’s methodology:

“Based on finding that intravenous provision with carnitine alone does not increase muscle carnitine accretion, and on the above-reevaluated data, it appears that the basis for carnitine with caffeine being able to increase muscle carnitine levels, and thereby manipulation of muscle metabolism and exercise performance, is uncertain.

Carnitine bioavailability in any group would have been 9.5%. This assessment would be in line with previously recorded values of 5%–18% carnitine bioavailability. It is firmly believed that low carnitine bioavailability is attributable to the inability of kidneys to reabsorb carnitine when the threshold concentration for tubular reabsorption (about 40–60 μmol/L) has passed this value.

The authors’ proposed long-term use of carnitine supplementation as an aid to improve fat oxidation in type II diabetes also seems to lack provision.”

https://physoc.onlinelibrary.wiley.com/doi/10.14814/phy2.15736 “LTE: Does caffeine truly raise muscle carnitine in humans?”

Two genetic studies:

“Our findings suggest that humans have lost a gene involved in carnitine biosynthesis. Hydroxytrimethyllysine aldolase (the second enzyme of carnitine biosynthesis) activity of serine hydroxymethyl transferase partially compensates for its function.”

https://www.researchsquare.com/article/rs-3295520/v1 “One substrate-many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse”

“Reported prevalence of primary carnitine deficiency (PCD) in the Faroe Islands of 1:300 is the highest in the world. The Faroese PCD patient cohort has been closely monitored and we now report results from a 10-year follow-up study of 139 PCD patients.

PCD is an autosomal recessive disorder that affects the function of organic cation transporter 2 (OCTN2) high-affinity carnitine transporters, that localizes to the cell membrane and transport carnitine actively inside the cell. Without proper functioning OCTN2 carnitine transporters, renal reabsorption of carnitine is impaired, and as a consequence, patients suffering from PCD have low plasma levels of carnitine. This can disturb cellular energy production and cause fatigue, but also in extreme cases lead to cellular dysfunction and severe symptoms of coma and sudden death.

PCD patients seem to adhere well to L-carnitine treatment, even though they have to ingest L-carnitine tablets at least three times a day. Overall mean L-carnitine dosage was 66.3 mg/kg/day.”

https://onlinelibrary.wiley.com/doi/10.1002/jmd2.12383 “Patients with primary carnitine deficiency treated with L-carnitine are alive and doing well—A 10-year follow-up in the Faroe Islands”

The average daily dose is (66.3 mg x 70 kg) = 4,641 mg. A third of this dose would be about 1.5 g.

The first study of Acetyl-L-carnitine dosing also suggested dosing L-carnitine three times a day because of 10-20% bioavailability.

A study with unhealthy humans:

“This retrospective study analyzed medical records of adult patients between March 2007 and April 2019, with presenting complaints of fatigue and lethargy. Acetyl-L-carnitine has physiological functions similar to L-carnitine but has higher bioavailability and antioxidant properties. This study confirmed that a triple combination therapy with γ-linolenic acid, V. vinifera extract, and acetyl-L-carnitine can improve arterial stiffness in patients.

Our study had some limitations:

  1. The study population may not be representative of the entire Korean adult population.
  2. The study did not have a medication-free control group. Instead, the comparison group comprised patients with medication compliance <80%.
  3. Drop-out rate of the triple-combination therapy (46.2%, 147/318) was relatively high, indicating the possibility of bias due to loss to follow-up.
  4. The study did not consider lifestyle factors such as smoking, diet, and physical activity level, which may affect arterial stiffness.
  5. The study did not examine interactions among drugs comprising the combination therapy, although all drugs are known to positively impact blood vessels.”

https://onlinelibrary.wiley.com/doi/10.1111/jch.14708 “Efficacy of γ-linolenic acid, Vitis vinifera extract, and acetyl-L-carnitine combination therapy for improving arterial stiffness in Korean adults: Real-world evidence”

This study’s acetyl-L-carnitine dose was 500 mg three times a day.

Wrapping up with two rodent studies:

“Acetyl L-carnitine (ALCAR) has proved useful in treatment of different types of chronic pain with excellent tolerability. The present work aimed at evaluating the anti-hyperalgesic efficacy of ALCAR in a model of persistent visceral pain associated with colitis.

The acetyl group in the ALCAR molecule can enhance cholinergic signalling by promoting synthesis of neurotransmitter acetylcholine, which plays an important role in both the enteric and central nervous systems. Acetylcholine signalling has significant antinociceptive effects in development of visceral pain, so it has been proposed as a therapeutic target.

ijms-24-14841-g001

ALCAR significantly reduced establishment of visceral hyperalgesia in DNBS-treated animals, though the interventive protocol showed a greater efficacy than the preventive one.

  • The interventive protocol partially reduced colon damage in rats, counteracting enteric glia and spinal astrocyte activation resulting from colitis.
  • The preventive protocol effectively protected enteric neurons from inflammatory insult.

These findings suggest the putative usefulness of ALCAR as a food supplement for patients suffering from inflammatory bowel diseases.”

https://www.mdpi.com/1422-0067/24/19/14841 “Anti-Hyperalgesic Efficacy of Acetyl L-Carnitine (ALCAR) Against Visceral Pain Induced by Colitis: Involvement of Glia in the Enteric and Central Nervous System

This study cited multiple animal studies that found acetyl-L-carnitine was effective for different types of pain. I’ve taken it every day for nineteen years, and haven’t noticed that effect.

“Repetitive mild traumatic brain injuries (rmTBI) may contribute to development of neurodegenerative diseases through secondary injury pathways. Acetyl-L-carnitine (ALC) shows neuroprotection through anti-inflammatory effects, and via regulation of neuronal synaptic plasticity by counteracting post-trauma excitotoxicity. This study aimed to investigate mechanisms implicated in etiology of neurodegeneration in rmTBI mice treated with ALC.

ALC is an endogenously produced carnitine metabolite present in tissue and plasma, and readily crosses the blood brain barrier, unlike its unacetylated form. ALC is also a commonly available nutritional supplement, with a known safety profile, and had been well-studied for its role in aiding β-oxidation of long chain fatty acids in the mitochondria.

While some studies have shown promise for improving clinical and psychometric outcomes in individuals with probable Alzheimer’s disease (AD) and mild cognitive impairment, other studies that included participants with moderate AD progression were less conclusive. It may be that this lack of improvement is related to a therapeutic window of opportunity. Once neurodegenerative mechanisms have commenced, a reversal of these processes is not attainable.

There is currently a lack of evidence for safe therapeutics that can be administered long-term to reduce the risk of individuals developing cognitive and neuropsychological deficits after rmTBIs. Prophylactic ALC treatment in a paradigm of neurotrauma may be a way to maximize its therapeutic potential.

While brain structures display differential vulnerability to insult as evidenced by location specific postimpact disruption of key genes, this study shows correlative mRNA neurodegeneration and functional impairment that was ameliorated by ALC treatment in several key genes. ALC may mitigate damage inflicted in various secondary neurodegenerative cascades – confirmed by improvements in behavioral and cognitive function – and contribute to functional protection following rmTBI.”

https://www.frontiersin.org/articles/10.3389/fphar.2023.1254382/full “Repetitive mild traumatic brain injury-induced neurodegeneration and inflammation is attenuated by acetyl-L-carnitine in a preclinical model”

I read many traumatic brain injury papers earlier this year, but only curated two in Brain endothelial cells. I came away thinking that there’s no permanent recovery from TBIs, as just symptoms are effectively treated.

Most TBIs happen to old people who have diminished brain reserves. I didn’t see studies that factored in evidence of what happened earlier in injured people’s lives that created TBI susceptibility but wasn’t remembered.

Unlike other years, I haven’t watched any football this season. It’s unsettling that transient entertainment value continues to take precedence over permanent effects on players’ lives.

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Guardians at your gates

gettingwell4 Immune system, Just me

This post emphasizes human agency in training our innate immune system. Otherwise, we are like agentless jellyfish I see almost every day on the beach, moved by tides and blown by winds, to their stranded graves.

I don’t cite studies here because none have been published regarding recent developments in human innate immune responses. Researchers keep their jobs by going along with the current narrative, no matter the evidence. I’ve presented evidence for taking personal responsibility for your own one precious life many times this decade.

There’s a JN.1 variant now that has emerged due to being evolutionarily driven to escape people’s adaptive immune systems who had one or more of the 2+ billion experimental gene therapy injections worldwide. People who are focused on this variant “tree” and missing the “forest” are allowing themselves to be herded for at least the tenth time this decade.

What can people who didn’t initially trust their innate immune systems, and subsequently slammed its functionality, do now in late 2023?

One avenue for redemption may be that taking off-patent anti-virals proven decades ago will work prophylactically. Even if people wait until they experience symptoms, luckily, the same proven anti-virals when administered early will also work therapeutically. Maybe people’s innate immune systems will recover, maybe they won’t, in which case they’ll hopefully keep taking anti-virals instead of unproven gene therapies.

Those who didn’t allow themselves to be propagandized this decade, and who initially trusted their innate immune systems’ functioning to maintain their health, will be fine. If they haven’t subsequently trained their innate immune systems, though, they may take longer to recover from another outbreak caused by people who acquiesced to experimental gene therapies.

I’ve trained my innate immune system every day for the past 19 years with yeast cell wall β-glucan because every disease is connected to the immune system. I’ve also exercised my endogenous antioxidant responses with weak pro-inflammatory isothiocyanates in broccoli sprouts every day for 3.5+ years.

Daily drills with weak threats will keep our body’s evolved systems tuned up and ready for real emergencies. Being sick takes away our ability to act independently, while simultaneously making us dependent on the broken medical care system.

So what is your preference? Be energized at sunrise?

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Or washed up on the beach?

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What you expect may not be what you find

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

I’m halfway through a 90-day trial of plasmalogens coincident with improving peroxisomal function via resistance exercise and time-restricted eating. I haven’t curated related 2023 papers I’ve read concerning plasmalogens, peroxisomes, sphingolipids, ceramides, and mitochondrial interactions with these, mainly because I haven’t seen human-pertinent aspects similar to Dr. Goodenowe’s efforts.

The 2023 papers I’ve read have more to do with researcher incentives rather than actual human benefits. I’d guess that researchers care about these related subjects to the extent that they want to be the first to publish arcane details about them, like peroxisomes in the parotid salivary gland.

One area I expected to see a difference at the regimen’s beginning was in my peripheral nervous system Schwann cells. Instead, I had taste and smell improvements in my primary olfactory nervous system olfactory ensheathing cells, which are highly similar to Schwann cells. I was also happy to experience an immediate halt to my ulnar nerve elbow pain after what I interpret as ProdromeNeuro effects and perhaps coincident ProdromeGlia effects on items upstream of Schwann cells.

Here are three papers on Schwann cells that I haven’t yet seen as applicable to my current regimen, starting with a 2022 review:

“We summarise contributions of neurotransmitter receptors in regulation of morphogenetic events of glial cells, with particular attention paid to the role of acetylcholine receptors in Schwann cell physiology. This redundant and complex integrated regulation system could be explained as a mechanism of preserving glial cell physiology. In case of a single receptor signalling dysfunction, other neurotransmitters can overcome the deficit, preserving functions of glia and health of the nervous system.

Increased knowledge in medicinal chemistry and in bioinformatics accompanied by drug delivery studies might open a fascinating therapeutic perspective for cholinergic mimetics for treatment of several nervous system pathologies, and in reducing neuroinflammation both in the central and peripheral nervous systems.”

https://www.mdpi.com/2227-9059/11/1/41 “Emerging Roles of Cholinergic Receptors in Schwann Cell Development and Plasticity”

A 2023 study investigated the vagus nerve’s Schwann cells’ impact with gut function:

“The vagus nerve is the longest extrinsic cranial nerve in the body. It regulates gut physiology through the intrinsic nervous system (myenteric and submucosal plexus) and enteric glial cells interactions, which participate in controlling intestinal absorption, secretion, immune homeostasis, and motility.

Normal intestinal motility is critical for nutrition assimilation and several biological functions. The loss of normal gut function aggravates inflammation, oxidative stress, and other cellular stressors.”

https://bmcbiotechnol.biomedcentral.com/articles/10.1186/s12896-023-00781-x “A critical role for erythropoietin on vagus nerve Schwann cells in intestinal motility”

I haven’t curated a Buck Institute for Research on Aging sponsored study for a while, since their 2015 A study of how “age” itself wasn’t a causal factor for wound-healing differences detracted from science and their 2020 Linear thinking about biological age clocks wasted resources.

This 2023 rodent study couldn’t investigate anything outside of Buck’s limited paradigm’s echo chamber. This sponsor would rather break their arms patting themselves on their backs pretending they’re advancing science than fund relevant human research successes that do advance science:

“Following peripheral nerve injury, successful axonal growth and functional recovery require Schwann cell (SC) reprogramming into a reparative phenotype. This work provides the first characterization of senescent SCs and their influence on axonal regeneration in aging and chronic denervation.”

https://www.embopress.org/doi/full/10.15252/emmm.202317907 “Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury”

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Building your plasmalogen savings account

gettingwell4 4-5 stars Advanced knowledge, Acetylcholine, Brain development, Cerebrum, Dopamine, Epigenetics, Immune system, Limbic system, Lower brain, Memory, Neurochemicals, Stress , , , , , ,

A webinar from earlier this week with Dr. Goodenowe, a clinical trial facilitator, and a physician:

From the Q&A segment:

“Is there a particular age where it’s recommended to test for plasmalogen levels? And what levels would be considered normal?

That’s a good question. That actually raises this whole concept of optimal health and this concept of aging.

The best way to think about it – we talked about this paycheck-to-paycheck situation, where as long as our bills are paid every day, technically we think we’re normal. But we still feel this sense of health anxiety – if you will – like we just don’t know if my car breaks down, or my water heater breaks down, do I have enough money to pay these events in my life?

That’s what health feels like to a lot of people, because they’re just kind of getting by. From a health perspective, they’re considered normal, but they have no reserve capacity, and they have no vitality in terms of health.

Plasmalogens are a type of molecule that you build a savings account of, over years, over decades. Your heart builds them up, your brain builds them up, and you slowly accumulate them. Then when you get an oxidative stress like what’s happening now in today’s world with all the covid and myocarditis and brain fog – a lot of these things are being caused because that reserve of plasmalogens has been depleted.

We want plasmalogens for a longevity perspective. There are other situations that can have low plasmalogens, other things can really knock your plasmalogens down.

So you want to start early, you want to build a savings account, and you want to maintain it. Maintain health and function, and create a sustained surplus for optimal health, for optimal neuromuscular performance.”

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Another reason to chew broccoli sprouts

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

This 2023 review explored a naturally produced antimicrobial:

“This review focuses on the role of abundant hypothiocyanous acid (HOSCN), a potent oxidant that kills bacteria but is non-toxic to human cells. Produced from thiocyanate (SCN−) and hydrogen peroxide (H2O2) in a variety of body sites by peroxidase enzymes, HOSCN has been explored as an agent of food preservation, pathogen killing, and even improved toothpaste.

Lactoperoxidase (LPO) is considered the main producer of HOSCN, and is secreted in saliva, tears, breastmilk, and lacrima of mammals. LPO regulates the oral microbiome and keeps breastmilk free of pathogens during the first few weeks after delivery. LPO has long been understood to play a role in prevention of dental caries.

Thiocyanate is mostly acquired from diet. Many food plants contain glucosinolates – precursors to isothiocyanates – found in vegetables of order Brassicales (broccoli, cabbages, turnips, mustard, horseradish, etc.).

HOSCN is likely to exist at substantial concentrations in the oral cavity and the respiratory tract, and is probably present under any inflammatory circumstances. Oxidative damage caused by HOSCN is largely reversible, since HOSCN cannot oxidize thiols to sulfinic or sulfonic acid.

mmi15025-fig-0002-m

The study of bacterial HOSCN stress response is in its infancy. Results summarized above suggest overlaps with both ROS and RCS responses, particularly in the areas of redox homeostasis (e.g., glutathione metabolism), cysteine metabolism, and prevention of protein aggregation, but considerable work needs to be done to more fully characterize this response.”

https://onlinelibrary.wiley.com/doi/10.1111/mmi.15025 “Hypothiocyanite and host–microbe interactions”

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What is the health utility of white blood cell type count ratios?

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

This post explores CBC ratios of neutrophils-to-lymphocytes (NLR) and lymphocytes-to-monocytes (LMR) as healthy biomarkers.

Uses of the neutrophils-to-lymphocytes ratio asserted:

A normal range of NLR is between 1–2, and values higher than 3.0 and below 0.7 in adults are pathological.

I saw only one study out of 151 references, reference 61 from 2017, that demonstrated a “below 0.7” range. All of its sampled subjects had sepsis or septic shock, though. Not exactly people from which to derive healthy parameters for the general population.

I looked through all 2023 papers of the 223 papers that cited this review. I didn’t see any that questioned a healthy status of a low neutrophils-to-lymphocytes ratio in humans. Almost all 2023 papers focused on diseases, not health, as if that’s what we want from researchers and medical professionals.

So if a review gets enough citations, its assertions become a fait accompli, elevated to an indisputable fact. Nevermind that unlike study researchers, reviewers aren’t bound to demonstrate evidence from tested hypotheses. Citing paper writers also aren’t obligated to actually read and understand what they cite.

I looked at papers that cited any of the four papers in Uses of the lymphocytes-to-monocytes ratio. There were hundreds of citations over the years, but I didn’t see any 2023 papers that related the LMR to health rather than disease.

The reciprocal monocytes-to-lymphocytes ratio may have prognostic value or “association with” other disease conditions. But do patients care about abstract values such as area under the curve?

Are hormone ratios useful in explaining health? Behavior? Neurobiology? Anything? had a similar situation:

“Analysis of individual variables offers more information and a more accurate picture of underlying relationships.”

This paper suggested by analogy that researching treatments to increase lymphocyte and/or decrease monocyte absolute counts rather than change ratios should be emphasized for health.

Labcorp blood tests from earlier this week came back yesterday. I’ll repeat a paragraph from another blog post that illustrates my viewpoint on them:

“Every explanation of those reference ranges, and optimal ranges built from all-cause mortality statistics, requires a suffix “of people who didn’t positively change their healthspan and lifespan.”

  • What value is there in optimizing (pick a measurement) against those outcomes?
  • Why compare my efforts, or results, or any other aspect of my life, to people who didn’t actionably care about their one precious life?”

Relevant white blood cell type counts and ratios from the current and three previous blood tests are:

nlr lmr

I’ve trained my innate immune system every day for the past 19 years with yeast cell wall β-glucan because every disease is connected to the immune system. I also haven’t been sick even one day this decade.

Let’s start with high-specificity C-reactive protein (hsCRP). Bookend values show very low inflammation over the past 2.5 years. Missing and regular CRP <1 values were due to medical professionals ignoring my written instructions.

Next are innate immune system monocytes, counts of which haven’t changed over the past 2.5 years. There have been no viruses, bacteria, fungi, or parasites that survived initial defenses. So monocyte-derived dendritic cell and macrophage activity hasn’t changed.

Next are adaptive immune system lymphocyte (T cells, natural killer cells, and B cells) counts that had a steady 31% increase from 1.6 to 2.1. It would be interesting to see which lymphocyte subtypes responded to the various therapeutic regimes I’ve implemented over these past 2.5 years. But I won’t become a lab rat to find out.

Last are innate immune system neutrophil counts, which our bone marrow makes copious amounts every day to fight infections. Mine have undergone a 43% decrease over the past 2.5 years. My bone marrow apparently doesn’t have metabolic imperatives to produce more short-lived neutrophils, probably because there isn’t a health emergency to immediately defend against.

To summarize, focusing on white blood cell type counts rather than their ratios better serves health purposes. The CBC test has coarse measures, though, so more refinement could be achieved.

Here’s an epigenetic clock summary of this week’s metabolomic results:

2023 epigenetic age

This summary from 2.5 years ago used the same calculations:

2021 epigenetic age

Maybe the additional 5.6 year difference in this first measurement instead of an opposite 2.5 year change along with chronological age is a signal that I’m getting more healthy. Maybe it’s noise. Recent memories argue against phenotypic age having anywhere near the impact of chronological age.

Comparing my two results against people who didn’t positively change their healthspan and lifespan has limited value, although this could reduce their denominator’s influence. We each have our life at stake, and bad things will happen on their own. If we want good things to happen, we have to make them happen.

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A good activity for bad weather days

gettingwell4 4-5 stars Advanced knowledge, Acetylcholine, Beliefs, Brain hemispheres, Cerebellum, Cerebrum, Dopamine, Epigenetics, Glutamate, Immune system, Limbic system, Lower brain, Memory, Neurochemicals, Stress, Thalamus , , , , , , , ,

A free educational series recorded in 2021-2022 available at https://drgoodenowe.com/dr-goodenowes-educational-seminars/ takes the viewer through underlying research and principles of Dr. Goodenowe’s approach to health. It’s advertised as lasting four hours, but took me two days to view.

The series’ discussions and references are background material to better understand later presentations and interviews. Points of interest included:

  • Seminar B100 shows that the metabolomic profile of people who regularly eat broccoli is different than others.
  • B109 clarifies how peroxisomal function is improved through resistance exercise and intermittent fasting.
  • C103 and C104 show how plasmalogens act against neurodegeneration (Parkinson’s disease and multiple sclerosis).

Texts below videos are additional information, not transcripts. C101 text is historically informative.

The B200 ProdromeScan tutorial will take more study. But unlike Labcorp tests, ordering a ProdromeScan requires using a practitioner in Dr. Goodenowe’s network.

I sent the following to Prodrome customer service earlier this month:

Please add me to your approved list for ProdromeScan.

Customer service replied:

“We only add health professionals to an approved list, not individuals.”

I responded:

Good morning. I looked at the websites of doctors who are associated with Dr. Goodenowe who are near me. All of them are too compromised for me to establish a doctor / patient relationship. But I’m glad they left up their blog posts from earlier this decade so I could see who they really were before I reached out to them.

I request an exception to the policy.

Customer service replied:

“There is no exception that can be made to this policy. You need to be a patient of a certified practitioner.”

I’ll escalate my request before my 90-day trial of Prodrome Glia and Neuro products ends so I can get an appropriate metabolomic status. Right now, I won’t involve someone I can’t trust just to know my ProdromeScan information that’s additional to next week’s Labcorp tests.

My treatment-result metabolomic data is probably not mature today on Day 29 of ProdromeGlia and ProdromeNeuro supplementation, resistance exercise, and intermittent fasting. I otherwise wouldn’t have experienced these two events:

I have a quibble with the series’ recommendations for taking N-acetyl cysteine. Relevant views and research:

Switch on your Nrf2 signaling pathway pointed out:

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

If someone bombs themself everyday with antioxidants, they’re doing nothing to improve training of their endogenous systems’ defensive functions. What happens when they stop bombing? One example was a 2022 human study that found GlyNAC-induced improvements dissolved back to baseline after supplements stopped.

Also, Precondition your defenses with broccoli sprouts highlighted NAC’s deleterious effects on autophagy and lysosome functions:

“TFEB activity is required for sulforaphane (SFN)-induced protection against both acute oxidant bursts and chronic oxidative stress. 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.”

If a secondary goal of taking NAC per is also necessary for the formation of glutathione, taurine can do that without an antioxidant bomb. Taurine supplementation will free up cysteine to do things other than synthesize taurine, like synthesize glutathione.

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Week 189 of Changing to a healthy phenotype with sprouts

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

1. I started eating 3-day-old microwaved Sango red radish sprouts ten weeks ago, but stopped two weeks ago due to stomach irritation. Earlier this year I tried them for a week using a different microwaving method, and found their glucoraphasatin pungency too much to stomach.

A technique of putting red radish sprouts in a bowl then into a Ziploc bag and using 40% power on my 1000W microwave for 10 seconds tamped their pungency down enough for a while. I use that technique every morning for a 3-day-old microwaved broccoli / red cabbage / mustard sprout mix.

I stopped eating Avena sativa oat sprouts in the evening because they don’t fit into a time-restricted eating regimen of ≤ 8 hours started last month. I still eat 3-day-old Avena sativa oat sprouts begun with 20 grams of hulled grains in the morning along with hulless Avena nuda oats.

I consider Avena nuda oats to be a sprouted grain food. After soaking 18-20 hours, about a quarter of the 82 g starting grains have visible sprouts when I eat them. 91% of Avena nuda oats visibly sprouted given a three-day germination period. So most of the Avena nuda oats that don’t show sprouts after soaking 18-20 hours have already started to germinate.

2. I’ve reduced food intake with TRE, and usually finish eating for the day before 4:00 p.m. This first item was reduced and the others deleted due to volume – too much food within 8 hours:

  • Advanced glycation end products-less chicken vegetable soup stretches for the prep day and three more days instead of two more days.
  • A daily avocado.
  • 85 g hard tofu.
  • 85 g precooked garbanzo / dark red kidney / pinto / black bean mix with untoasted sesame seeds. Will probably restart this the next time TPTB cause empty grocery store shelves.

I changed these two items after my sense of smell and taste improved:

  • I split 283 g of sliced white, crimini, portobello, and shitake mushrooms into the three leftover AGE-less chicken vegetable soup servings rather than into all four servings. Don’t need an umami bomb for prep day soup to taste good.
  • Stopped adding 3 g inulin daily to green tea. Don’t need a sweet taste.

Usually drink three cups of green tea and a cup of aluminum-free coffee before noon.

3. Supplements changed with TRE. Although the ProdromeNeuro loading dose and the 3-day-old broccoli / red cabbage / mustard sprout mix both have about 30-35 calories, I use the later mix as the start of TRE.

When I think an item’s desired results could be antagonized by having other items in the stomach, I’ll take it without eating anything else an hour before or an hour after. I’ll use meal numbers below rather than breakfast / lunch / dinner nomenclature as divisions among them are compressed.

Before Meal 1
– 3.2 g ProdromeNeuro, with nothing else an hour before or after
– 1.5 g yeast cell wall β-glucan (Glucan 300), with nothing else an hour before or after

Meal 1
– 3-day-old microwaved broccoli / red cabbage / mustard sprouts started from 10.7 g of seeds, with nothing else an hour before or after

Meals 2, 3, and 4
– 5 g total taurine
– 3.75 g total glucosamine hydroxychloride / 3 g total chondroitin sulfate, Kirkland Signature
– 3 g total acetyl-L-carnitine, Now
– 1.8 g total chondroitin sulfate, Now
– Hyaluronic acid, Nature’s Lab, 1 serving total
– 9 mg total boron, Swanson Triple Boron Complex

Meals 2 and 4
– Balance oil (total 1400 mg linoleic acid / 350 mg linolenic acid)
– 3 g total betaine anhydrous (TMG), Now
– 2 g total arginine alpha-ketoglutarate, Swanson

Meal 2 only
– Minerals and vitamins (RDA mainly), Kirkland Signature Daily Multi
– 25 mcg D3

Meal 3 only
– 56.7 g desalted capers
– 28.35 g walnuts
– 5 g creatine
– 600 mcg Vitamin K2 MK-7, Now

Meal 4 only
– 1.2 g lecithin, Now
– 30 mg zinc monomethionine / 0.3 mg copper, Now
– 25 mg lutein / 5 mg zeaxanthin
– 50 mcg D3

After Meal 4
– 3.2 g ProdromeGlia, with nothing else an hour before or after

4. I’ll get blood tests next week without involving medical professionals other than Labcorp employees. I’ll compare results to a May 2023 annual physical done in the week I started retirement to see whether I’ve changed my phenotype to be more healthy during these less-stressful past six months.

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