Natural sulforaphane effects

This 2022 rodent cell study used the natural form of sulforaphane to replicate experiments performed with mixtures of its natural and unnatural forms:

“Natural sulforaphane (SFN) exists as a single enantiomer with a RS absolute configuration. Most studies focusing on its biological activities, in particular its anti-inflammatory and antioxidant activities, have been conducted using its racemic (rac) form. rac-SFN has shown these effects in several in vitro and in vivo models.

(R)-sulforaphane

These findings demonstrate that (R)-SFN was able to:

  • Modulate inflammatory response and oxidative stress induced by LPS stimulation in murine peritoneal macrophages;
  • Reduce pro-inflammatory enzyme expression (iNOS, COX-2 and mPGES-1) and cytokine production (IL-1β, IL-6, IL-17, IL-18 and TNF-α);
  • Inhibit MAPK, JAK2/STAT-3, and canonical and non-canonical inflammasome signaling pathways;
  • Reduce NO and ROS levels and up-regulate the Nrf-2/HO-1 axis; and
  • Modulate epigenetic changes through histone methylation (H3K9me3) and deacetylation (H3K18ac).

(R)-SFN could be a new epinutraceutical compound useful for management of several immunoinflammatory diseases.”

https://www.mdpi.com/1424-8247/15/8/966/htm “Immunomodulatory Effects of (R)-Sulforaphane on LPS-Activated Murine Immune Cells: Molecular Signaling Pathways and Epigenetic Changes in Histone Markers”


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Epigenetic effects of plasma concentrate

“We use data from a safety study (n = 18, mean age 74) to investigate whether human umbilical cord plasma concentrate (hereinafter Plasma Concentrate) injected weekly (1 ml intramuscular) into elderly human subjects over a 10-week period affects different biomarkers, including epigenetic age measures, standard clinical biomarkers of organ dysfunction, mitochondrial DNA copy number (mtDNA-CN), and leukocyte telomere length.

More than 20 clinical biomarkers were significantly and beneficially altered. Telomere length and mtDNA-CN were not significantly affected by treatment.

An increase in entropy means that the methylome becomes noisier. We found that entropy was significantly decreased after treatment. Decreased entropy may implicate rejuvenation of the epigenetic landscape after plasma concentrate treatments.

changes in methylation entropy

Treatment reduced DNA methylation-based GrimAge by an average of 0.82 years, suggesting a reduction in morbidity and mortality risk. By contrast, no significant results could be observed for epigenetic clocks that estimate chronological age.

Our study lends credence to the notion that there are youth-promoting factors in the secretome of umbilical cord plasma. This conclusion has also been reached by other researchers that have provided treatment with stem cells, which do not work by plasma dilution but primarily by providing humoral factors and changing the microenvironment of cells and tissues. While there may be youth-promoting microvesicles or humoral factors that are at work, we do not want to rule out the possibility that it is ‘young and undamaged’ albumin that leads to the improvements noted, especially in light of recent evidence for such a mechanism.

This first human epigenetic clock study of plasma concentrate treatments revealed age-reversal effects according to a well-established DNA methylation-based estimator of morbidity and mortality risk. Future placebo-controlled replication studies are warranted with a larger number of participants over a longer study period, which our laboratory has undertaken to pursue.”

https://onlinelibrary.wiley.com/doi/10.1111/acel.13696 “Umbilical cord plasma concentrate has beneficial effects on DNA methylation GrimAge and human clinical biomarkers”


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Improving dietary fiber research

Two 2022 papers on aspects of dietary fiber research, starting with a review:

“Considerable attention has been given to unraveling the interaction between fiber type and gut microbiota utilization, focusing mainly on single, purified fibers. Studying these fibers in isolation might give us insights into specific fiber effects, but neglects how dietary fibers are consumed daily and impact our digestive tract: as intrinsic structures that include the cell matrix and content of plant tissues.

Food processing per se is not health-detrimental. Certain foods are barely digestible without any processing, and for specific populations, e.g. those suffering from malnutrition or diseases, food processing is crucial. However, increased digestibility has resulted in negative health outcomes related to obesity and welfare diseases.

whole grain

Intrinsic structural features of plant cells likely slow down fiber fermentation, inducing a lag phase, but do not necessarily reduce the absolute amount of short-chain fatty acids (SCFA) produced. Consequently, there is a gradual release of SFCA, which means that SCFA production is not restricted to the proximal colon but spread throughout the whole colon, including its distal parts, benefiting local, mucosal health.

This translates into beneficial, systemic, peripheral effects as distal SCFA infusion in vivo has shown to induce more pronounced effects on biomarkers than proximal. Delayed fermentation of intrinsic fibers presents a highly relevant feature that isolated, single fibers do not have.

Instead of further processing our already extensively processed foods to create new products, we should minimize this processing, and exploit health benefits associated with the original cell matrix of plant tissues.”

https://www.frontiersin.org/articles/10.3389/fimmu.2022.954845/full “Intrinsic dietary fibers and the gut microbiome: Rediscovering the benefits of the plant cell matrix for human health”


Reference 115 was a human study by the same researchers:

“We investigated the impact of dried chicory root in a randomised, placebo-controlled trial with 55 subjects at risk for type 2 diabetes. Evidence for a trophic chain including Bifidobacterium and Anaerostipes spp. was recapitulated by in vitro incubations that resulted in high levels of butyrate and propionate production from the treatment product.

butyrate and propionate microbial network

We observed a simultaneous increase in faecal and circulating SCFA levels, and a marked improvement in dynamic markers of glucose control. In subjects with a low relative abundance of Blautia spp. – a genus that previously has been associated with T2D – static glycaemic markers also decreased pronouncedly.

Our results demonstrate a strong modulatory potential on gut health and microbial metabolism by native inulin and cell wall fibres pectin, cellulose and hemicellulose in the intrinsic form of dried chicory roots.”

https://www.cambridge.org/core/journals/gut-microbiome/article/dried-chicory-root-improves-bowel-function-benefits-intestinal-microbial-trophic-chains-and-increases-faecal-and-circulating-short-chain-fatty-acids-in-subjects-at-risk-for-type-2-diabetes/6209AEAFBDDB181197F22AE24388186B# “Dried chicory root improves bowel function, benefits intestinal microbial trophic chains and increases faecal and circulating short chain fatty acids in subjects at risk for type 2 diabetes”


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Garlic vs. broccoli

This 2022 human study compared effects of two supplements:

“We test the hypothesis that consuming glucoraphanin (from broccoli) or alliin (from garlic) results in the accumulation of sulforaphane and alliin and their associated metabolites in the human prostate gland in a randomised, double-blinded, 2 × 2-factorial, dietary supplement, four-week intervention study.

The predominant sulphur-containing metabolite in garlic is alliin, which is odourless and non-volatile. When the plant tissue is damaged, alliinase enzymes rapidly convert alliin to allysulfenates that condense to form allicin and other thiosulfinates, predominantly γ-glutamyl S-allyl-L cysteine (γ-SAC) and S-allyl-L cysteine (SAC).

The BroccoMax/GRN supplements (530 mg) contained 97.7 ± 6.70 µmol glucoraphanin. The Kwai/alliin supplements (715 mg) contained four garlic-derived metabolites: alliin (35.2 ± 0.52 µmol), γ-SAC (19.3 ± 1.91 µmol), SAC (1.8 ± 0.16 µmol), and allicin (21.4 ± 2.10 µmol).

Mean excretion of sulforaphane and its metabolites as a percentage of ingested glucoraphanin [aka bioavailability] was 56.21% (range 21–91%, SD ± 18.66).

sulforaphane bioavailability

Alliin was detected within the prostate of every participant. Estimation of dietary intake of alliaceous vegetables is challenging due to their widespread presence in processed foods, and it is likely that intake is often underestimated.

We provide evidence that sulforaphane can be detected in human prostate tissue following regular consumption of glucoraphanin supplements. In contrast, alliin and associated metabolites were not more abundant in prostates of men receiving the alliin garlic-derived supplement. It is conceivable that alliin does accumulate in human prostate tissue, but its turnover is much slower than that of sulforaphane so that a longer allium-free diet is required prior to an intervention to assess its accumulation.

Accumulation of sulforaphane and presence of alliin in prostate tissue, as demonstrated in this study, may result in local effects on healthy and cancerous cells through a variety of mechanisms. This may explain the reduced risk of prostate cancer incidence and progression following consumption of cruciferous and alliaceous vegetables.”

https://www.mdpi.com/2072-6643/14/16/3263/htm “Accumulation of Sulforaphane and Alliin in Human Prostate Tissue”


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Epigenetic clocks so far in 2022

2022’s busiest researcher took time out this month to update progress on epigenetic clocks. If I curated every study he’s contributed to, it would require at least three blog posts a week. I’ll link to a few he’s posted in August 2022 that are more appreciated in the researcher community.

“In my lab, we are looking for clocks that apply to multiple species at the same time, for example, universal pan-mammalian clocks. It’s all about enhancing translation.

If you have an intervention that rejuvenates a mouse, a rat, a dog, and a cat according to the same clock, then chances are high that it will also work in humans. Naked Mole-Rat Hyaluronan Synthase 2 Promotes Longevity and Enhances Healthspan in Mice

Several groups, including mine, are working on single cell methylation clocks. Researchers are building clocks that respond to lifestyle interventions, such as exercise.

Moving away from methylation, it would be nice to build similar clocks for other ‘omics’ data. Many researchers build clocks on the basis of other omics data, such as for chromatin, proteomics, and gene expression.

There are different platforms, but they all attempt to measure the same thing: biological age. LINE-1 RNA causes heterochromatin erosion and is a target for amelioration of senescent phenotypes in progeroid syndromes

Epigenetic clocks are ‘life course clocks.’ I don’t know any other biomarkers of aging that applies to fetal tissues as well, because most other biomarkers measure organ dysfunction. Epigenetic profiling and incidence of disrupted development point to gastrulation as aging ground zero in Xenopus laevis

There’s this company called Intervene Immune, founded by Greg Fahy, and they are using GrimAge and other epigenetic clocks in clinical trials. They are doing a Phase II clinical trial. By the way, I’m one of the participants.

I could name several other groups who are using epigenetic clocks in clinical trials. It would be interesting if more people would measure epigenetic age in clinical trials in humans, at least as a secondary outcome, because there’s always an opportunity to make a discovery.

If you compare GrimAge to other biomarkers, such as cholesterol or glucose levels, you will see similar noise levels there. Epigenetic clocks are remarkably robust compared to what else is used in the clinic. I would say that the issue with technical noise in epigenetic clocks has been solved.

I’m really glad that different companies and researchers pursue different avenues, since it diversifies our risk. If one of these approaches works, it will change the world.”

https://www.lifespan.io/news/steve-horvath-on-the-present-and-future-of-epigenetic-clocks/ “Steve Horvath on the Present and Future of Epigenetic Clocks”


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Don’t bother eating broccoli sprouts if you’re old?

I try to not curate research that wastes resources. Couldn’t help but present this 2022 rodent study:

“We aimed to evaluate if sulforaphane (SFN) long-term treatment was able to prevent age-associated cognitive decline in adult (15-month-old) and old (21-month-old) female and male rats.

Our results showed that SFN restored redox homeostasis in brain cortex and hippocampus of adult rats, preventing cognitive decline in both sexes. However, redox responses were not the same in males and females.

Old rats were not able to recover their redox state as adults did, but they had a mild improvement. These results suggest that SFN mainly prevents rather than reverts neural damage; though, there might also be a range of opportunities to use hormetins like SFN, to improve redox modulation in old animals.”

https://link.springer.com/article/10.1007/s10522-022-09984-9 “Long-term sulforaphane-treatment restores redox homeostasis and prevents cognitive decline in middleaged female and male rats, but cannot revert previous damage in old animals” (not freely available)


These researchers cited Sulforaphane in the Goldilocks zone for hormetic effects of sulforaphane, so I asked:

“Did you develop any preliminary dose/response data for stating ‘there might also be a range of opportunities to use hormetins like SFN to improve redox modulation in old animals’?”

They cited Broccoli sprouts activate the AMPK pathway for long-term effects of a small sulforaphane dose, so I asked:

“Also, the three studies cited for ‘0.5 mg/Kg, i.e. 2.82 μmol/Kg BW for 3 months’ were all mouse studies. Since this was a rat study, wouldn’t there be increased dose and duration equivalencies?”

I’ll update this blog post in the event either of my questions to these researchers are answered.

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Sulforaphane nose drops

This 2022 rodent study compared capabilities of intranasal nanoparticle sulforaphane and free sulforaphane to mitigate brain damage caused by a common cancer treatment:

“Non-invasive intranasal (IN) trafficking of therapeutic agents with nanocarriers can enhance efficacy of drug delivery, biodistribution, bioavailability, and absorption against enzymatic degradation and extracellular transportation. Direct IN trafficking of nanocarriers is expected to reduce drug wastage, administration frequency, and undesirable adverse effects.

The nasal route for brain-targeted delivery of sulforaphane (SF) loaded within iron oxide nanoparticles (Fe3O4-NPs) was based on improving physicochemical stability of SF, and to enhance its bioavailability by avoiding oral route drawbacks like extensive first-pass metabolism and intestinal drug degradation.

Cisplatin (CIS) significantly induced a significant increase in acetylcholinesterase activities and lipid peroxides, and a significant decrement in glutathione and nitric oxide contents. We aimed to explore the nanotherapeutic potential of intranasally delivered SF loaded within Fe3O4-NPs (N.SF) against CIS-induced neurotoxicity through different biochemical, behavioral, and histological investigations.

hippocampus damage

Treatment with N.SF was more capable of mitigating both CIS-induced striatal and cortical injuries. IN treatment with either SF or N.SF showed equal alleviative potential regarding CIS-induced hippocampal or cerebellar injury.

These encouraging results demonstrated the potential use of iron-oxide NPs as neurotherapeutic agents, and confirmed the possibility of developing a novel promising and non-invasive intranasal delivery system for treatment of CIS-induced neurotoxicity.”

https://link.springer.com/article/10.1007/s12640-022-00555-x “Neuroprotective Potential of Intranasally Delivered Sulforaphane-Loaded Iron Oxide Nanoparticles Against Cisplatin-Induced Neurotoxicity”


I found this study from it citing a paper in Do broccoli sprouts treat migraines?

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Non-patentable boron benefits

To follow up Is boron important to health? I’ll highlight a 2022 review of boron intake:

“Boron is essential for activity of several metabolic enzymes, hormones, and micronutrients. It is important for growth and maintenance of bone, reduction in inflammatory biomarkers, and increasing levels of antioxidant enzymes.

The average person’s daily diet contains 1.5 to 3 milligrams of boron. Boron intakes of 1–3 mg/day have been shown to improve bone and brain health in adults when compared to intakes of 0.25–0.50 mg/day.

One week of 10 mg/d boron supplementation resulted in a 20% reduction in inflammatory biomarkers TNF-α, as well as significant reductions (nearly 50%) in plasma concentrations of hs-CRP and IL-6. Calcium fructoborate, a naturally occurring, plant-based boron-carbohydrate complex, had beneficial effects on osteoarthritis (OA) symptoms. A double-blind study in middle-aged patients with primary OA found that all groups except the placebo group saw a reduction in inflammatory biomarkers after 15 days of food supplementation with calcium fructoborate.

Dietary boron intake significantly improves brain function and cognitive functioning in humans. Electroencephalograms showed that boron pharmacological intervention after boron deficiency improved functioning in older men and women, such as less drowsiness and mental alertness, better psychomotor skills (for example, motor speed and dexterity), and better cognitive processing (e.g., attention and short-term memory). Boron compounds can help with both impaired recognition and spatial memory problems.

We discussed the role of boron-based diet in memory, boron and microbiome relation, boron as anti-inflammatory agents, and boron in neurodegenerative diseases. Boron reagents will play a significant role to improve dysbiosis.”

https://www.mdpi.com/1420-3049/27/11/3402/htm “The Role of Microbiome in Brain Development and Neurodegenerative Diseases”


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If you lose mobility, you lose cognitive function

This 2022 human study used four epigenetic clocks to assess aging:

“This cohort study was a secondary analysis of 3 Women’s Health Initiative (WHI) ancillary studies among 1813 women eligible to survive to age 90 years by end of study period. The study found that increased epigenetic age acceleration (EAA) as measured by 4 epigenetic clocks was associated with lower odds of survival to age 90 years with intact mobility; results were similar when including intact cognitive functioning.

This study benefited from a large, racially and ethnically diverse sample of women who were followed up to at least age 90 years with detailed longitudinal data on a host of lifestyle and health history factors. This study is generalizable to WHI women owing to use of IPW weights, and may be generalizable to a large range of women in the United States.

zoi220662t1_1658260078.05222

Among 1813 women, there were:

  • 464 women who survived to age 90 years with intact mobility and cognitive functioning;
  • 420 women who survived to age 90 years without intact mobility and cognitive functioning; and
  • 929 women who did not survive to age 90 years.

Only 29 women were reclassified from the healthy longevity group to surviving to age 90 years without intact mobility and cognitive functioning. Although it was of great interest to investigate the association between EAA and survival to age 90 years with intact cognitive function independently, this study population did not have sufficient numbers of women who experienced loss of cognitive function (without loss of mobility) to do so.”

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2794706 “Analysis of Epigenetic Age Acceleration and Healthy Longevity Among Older US Women”


Early humans who lost mobility in our African savanna ancestral environment during the Pleistocene Epoch (approximately 2.6M to 12K years ago) were prey. I highly doubt that immobile individuals successfully became our ancestors.

I downgraded this study because these researchers misguidedly soiled worthwhile findings with BMI and education level non-causal associations. They intentionally did this, as several of them were coauthors of the execrable Epigenome-wide meta-analysis of BMI in nine cohorts: examining the utility of epigenetic BMI in predicting metabolic health.

See Findings, or fun with numbers? and Does a societal mandate cause DNA methylation? for opposing research.


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Findings, or fun with numbers?

This 2022 rodent study investigated bone mass phenotypes and sulforaphane:

“Mouse strains can have divergent basal bone mass, yet this phenotype is seldom reflected in the design of studies seeking to identify new modulators of bone resorption by osteoclasts. Sulforaphane exerts inhibitory effects on in vitro osteoclastogenesis in cells from C57BL/6 mice. We explore whether a divergent basal bone mass in different mouse strains is linked both to in vitro osteoclastogenic potential and to SFX-01 sensitivity.

osteoclasts in three mouse strains

Powerful antioxidants are an alternative to achieve beneficial bone effects and avoidance of osteoporotic bone loss. Sulforaphane (SFN) is a natural antioxidant found at high levels (as glucoraphanin) in cruciferous vegetables. SFN activates the NRF2 pathway and has anti-inflammatory effects, protecting against oxidative stress in many cell types.

These findings suggest that BM cells derived from animals with a high in vivo bone mass are less sensitive to M-CSF and RANKL in vitro leading to lower osteoclastogenesis. They also support the hypothesis that similar sensitivity extends to inhibitory effects of SFX-01 on osteoclast formation/function.

It is important to stress that osteoclasts generated in these strains may simply undergo multinucleation in a manner related to their underpinning genetics, and that by coincidence alone this is matched to their bone mass.”

https://onlinelibrary.wiley.com/doi/10.1002/cbf.3734 “High bone mass in mice can be linked to lower osteoclast formation, resorptive capacity, and restricted in vitro sensitivity to inhibition by stable sulforaphane”


I curated this study primarily for its honesty. I’ll link this post to future posts of studies where researchers lack similar honesty.

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Broccoli sprouts and your brain

A 2022 review of Nrf2 signaling hilariously avoided mentioning sulforaphane, although of ~4,000 sulforaphane published articles, two were cited. I’ll curate it anyway to highlight referenced brain effects.

“A good stability of NRF2 activity is crucial to maintain redox balance and therefore brain homeostasis. In this review, we have gathered recent data about the contribution of the NRF2 pathway in the healthy brain as well as during metabolic diseases, ageing, and ageing-related neurodegenerative diseases.

A functional NRF2 system is important to regulate both neuroinflammation, i.e., activation of microglia and astrocytes, and oxidative stress in the brain. NRF2 and NF-κB transcription factors regulate cellular responses to inflammation and oxidative stress in order to maintain brain homeostasis. Both pathways have been described to inhibit each other.

Nrf2 brain aging

Future challenges will be to establish novel therapies to:

  • Increase NRF2 activation in specific cell types and/or brain regions; and
  • Modulate NRF2 pathway in senescent cells.

Modulation of NRF2 signalling pathway by using specific food products [like unmentioned broccoli sprouts] and phytochemicals [like unmentioned sulforaphane], dietary supplements [like unmentioned Vitamin D3], drugs, and epigenetic modifiers, alone or in combination, will help to limit inflammatory diseases, ageing process, and subsequently ageing-related diseases.”

https://www.mdpi.com/2076-3921/11/8/1426/htm “Normal and Pathological NRF2 Signalling in the Central Nervous System”


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Eat broccoli sprouts for your offspring

This 2022 rodent study investigated effects of glucoraphanin supplementation during pregnancy and lactation:

“We investigated whether dietary intake of sulforaphane glucosinolate (SGS [properly termed glucoraphanin]) during pregnancy and lactation influenced composition of gut microbiota in offspring:

  • Dietary intake of SGS during pregnancy and lactation caused significant changes in diversity of gut microbiota in 3-week-old offspring (SGS-3W) and 10-week-old offspring (SGS-10W).
  • Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in SGS-10W after injection of lipopolysaccharide were significantly lower than those of CON-10W group.
  • There were sex differences of gut microbiota composition in both SGS-3W and SGS-10W offspring.

glucoraphanin during pregnancy and lactation

This study has some limitations:

  1. We did not investigate mechanisms of how dietary intake of SGS during pregnancy and lactation modulated gut microbial communities in offspring.
  2. We found several signaling pathways in beneficial effects of SGS food pellet, and further study of the role of maternal intake of SGS food in these pathways is needed.
  3. We did not investigate mechanisms of relationships between maternal intake of SGS and long-term anti-inflammatory action in adult offspring, and further detailed study including epigenetic modification is needed.

These data suggest that dietary intake of SGS during pregnancy and lactation might produce long-lasting beneficial effects in adult offspring through persistent modulation of gut microbiota. It is likely that modulation of gut microbiota by maternal nutrition may confer resilience versus vulnerability to stress-related psychiatric disorders in offspring.”

https://www.sciencedirect.com/science/article/pii/S0955286322001681 “Long-lasting beneficial effects of maternal intake of sulforaphane glucosinolate on gut microbiota in adult offspring”


This study published results of a mother’s glucoraphanin intake where offspring never ate glucoraphanin, with beneficial effects at both 3 weeks (~prepubescent human) and 10 weeks (~young human adult). Maybe future studies will continue this paradigm on to a second or third generation to see whether there are also transgenerational epigenetic effects.

This study’s methods extracted glucoraphanin from 1-day-old broccoli sprouts into a powder containing 135 mg (0.31 mmol) glucoraphanin per gram. Each 1 kg of of treatment chow included pellets containing (2.3 mmol / 0.31 mmol) x 135 mg = 1 gram of broccoli sprout powder, 0.1% of food intake.

Per Drying broccoli sprouts, dried 3-day-old broccoli sprouts contain 10% moisture, and fresh 3-day-old broccoli sprouts contain 82.6% moisture. A gram of 1-day-old broccoli sprout powder may be an approximate equivalent of (.826 / .1) = 8 grams fresh 3-day-old broccoli sprouts for a mouse / kg of daily food intake. A human equivalent dose is (.826 / .1) x .081 x 70 kg = 47 grams of fresh 3-day-old broccoli sprouts / kg of daily food intake.

That’s about how much 3-day-old, microwaved, glucoraphanin-containing broccoli and red cabbage sprouts I eat every day, starting from 7.2 grams of seeds. I sprout another 3.5 grams of yellow mustard seeds into the mixture for taste.


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Week 120 of Changing to a youthful phenotype with sprouts

It was time for an annual physical last Wednesday. My focus was to see whether reducing sulforaphane intake per Week 87 had the desired effect on thyroid measurements.

That and other adjustments did! Readings of TSH 2.91 (0.45 – 4.50 uIU/mL), free T4 1.22 (0.82 − 1.77 ng/dL), and free T3 2.4 (2.0 – 4.4 pg/mL) were all in-range. 🙂

thyroid


I won’t repeat the Week 63 workbook calculations done after last year’s annual physical. To me, that’s another form of magical thinking.

Every one 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?

I’m not deflecting with poor measurements:

  • 3 of the 5 values in last year’s optimal ranges got better, and the other 2 stayed the same; and
  • 2 of the 4 values that weren’t in last year’s optimal ranges came into those ranges, and the other 2 got better but stayed outside an optimal range.

We each have a lot at stake. Bad things like diseases of old age happen on their own. If we want good things to happen, we have to make them happen.

Consider this from The impact of transgenerational epigenetic inheritance and early life experiences:

“Every disease is connected to the immune system.”

Are people making good choices every day for their immune systems?

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Eat broccoli sprouts for metabolic syndrome

This 2022 rodent study investigated sulforaphane’s effects on insulin resistance:

“Insulin resistance is one of the defining clinical traits of metabolic syndrome, which represents a constellation of metabolic disorders, mainly comprising obesity, type 2 diabetes mellitus, atherogenic dyslipidemia, and hypertension. This study aimed to investigate therapeutic effects and potential mechanisms of sulforaphane (SFN) on high-fat diet (HFD)-induced insulin resistance. Control chow diet was 10 kcal% fat, and HFD was 60 kcal% fat.

  • SFN was found to effectively reduce body weight, fasting blood glucose, and hyperlipidemia, and improve liver function in HFD-fed mice.
  • SFN led to increased expression of antioxidant genes downstream of Nrf2, and decreased accumulation of lipid peroxides MDA and 4-HNE.
  • SFN significantly reduced glutathione peroxidase 4 (GPx4) inactivation-mediated oxidative stress by activating the AMPK and Nrf2 signaling pathways.

Data suggested that GPx4 could be a key target through which SFN might activate Nrf2/ARE signaling pathway to decrease the extent of insulin resistance induced in HFD-fed mice. Taken together, SFN ameliorated HFD-induced insulin resistance by activating the AMPK-Nrf2-GPx4 pathway, providing new insights into SFN as a therapeutic compound for alleviation of insulin resistance.”

https://www.sciencedirect.com/science/article/pii/S075333222200662X “Sulforaphane alleviates high fat diet-induced insulin resistance via AMPK/Nrf2/GPx4 axis”


This study’s sulforaphane dose was the same as Eat broccoli sprouts for your heart and Broccoli sprouts activate the AMPK pathway at 0.5 mg / kg. It was administered five times a week for 8 weeks to a subgroup of HFD-fed mice starting after 8 weeks of HFD.

A human equivalent oral dose to these three studies’ subcutaneous doses would be a low (0.5 mg x .081) x 70 kg = ~3 mg sulforaphane. Per Eat broccoli sprouts for your gut, my sulforaphane intake is six times that every day.

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Is boron important to health?

Three papers on boron, starting with a 2022 review:

“Boron-containing compounds (BCC) have effects in the metabolism of living organisms. Information regarding effects and interaction of these compounds was compiled, and potential applications for treating human metabolic disorders was suggested.

Dietary boron supplementation affects metabolism of calcium, magnesium, triglycerides, glucose, amino acids, reactive oxygen, nitrogen species, and hormones such as 17β-estradiol, calcitonin, and 25-hydroxy-cholecalciferol. When food is boron-deprived, there are adverse effects like depressed growth, reduced serum steroid hormone concentrations, changes in plasma and organ calcium and magnesium concentrations, plasma alkaline phosphatase, and bone calcification on animal biological functions.

boron effects

Exploration of basic BCC as metabolism regulators is expanding. Although mechanisms of action are uncertain, limitation of damage induced by reactive species, inflammatory modulation, or activities on some enzymes and membrane transporters are often related to reported effects.

An increasing number of new BCC are emerging as potential tools for prevention, diagnosis, and therapy of metabolism maladies such as diabetes, metabolic syndrome, osteoporosis, cardiovascular, and liver diseases. For those innovative BCC, mechanisms of action are often clear.”

https://link.springer.com/article/10.1007/s12011-022-03346-9 “Boron‑Containing Compounds for Prevention, Diagnosis, and Treatment of Human Metabolic Disorders” (not freely available) Thanks to Dr. Marvin A Soriano-Ursúa for providing a link to a freely available document.


A second paper was a 2021 human study:

“In our elderly population-based sample, a boron-rich diet appeared to be characterized by high intakes of plant foods presumed to be healthy, low intakes of plant foods presumed to be less healthy, and low intakes of all kinds of animal foods.

Higher plasma boron concentrations were related to lower BMI and circulating concentrations of CRP. Plasma boron concentrations were associated with age, phosphate, and plasma lipid metabolism, and showed seasonal variations.

Human intervention studies are warranted to derive causal relationships of circulating and dietary boron with human health and metabolism. Robust databases on boron content of foods are needed to facilitate investigation of dietary boron intake in human studies.

Clarification of the non-/essentiality of trace element boron for human health will form the basis to derive recommendations for a dietary boron intake being sufficient to exert boron’s proposed beneficial physiological roles.”

https://link.springer.com/article/10.1007/s00394-021-02730-w “Plasma boron concentrations in the general population: a cross-sectional analysis of cardio-metabolic and dietary correlates”

As noted in this study, public agencies don’t consider dietary boron content important enough to include in public databases. My daily boron dietary intake estimated from published private databases is:

  • Walnuts, 1.63 mg x (28.3 g / 100 g) = .5 mg
  • Red kidney beans, 1.4 mg x (12 g / 100 g) = .2 mg
  • Chickpeas, 0.71 mg x (40 g / 100 g) = .3 mg
  • Celery, 0.5 mg x (72 g / 100 g) = .4 mg
  • Carrots, 0.3 mg x ( 76 g / 100 g) = .3 mg
  • Coffee .07 mg x 3 cups = .2 mg

2 mg boron daily dietary total


A third paper was a 2022 rodent study:

“Sodium pentaborate pentahydrate (NaB) 1 and 2 mg elemental B/kg supplementation induces the anagen phase in rats via Wnt-1, β-catenin, VEGF, PDGF, and TGF-β1 signaling pathways, which are important molecular mechanisms involved in hair growth.

NaB 4 mg B/kg suppresses these pathways and adversely affects hair growth.”

https://www.sciencedirect.com/science/article/abs/pii/S0946672X22000876 “Sodium pentaborate pentahydrate promotes hair growth through the Wnt/β-catenin pathway and growth factors” (not freely available)

A human equivalent of this study’s rat 1 mg elemental boron intake is (1 mg x .162) x 70 kg = 11 mg.


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