Month: October 2022

Eat broccoli sprouts for longevity

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

This 2022 rodent study investigated effects of broccoli sprouts intake on health and longevity:

“The objective of this study was to assess effects of long-term broccoli sprouts (BrSp) feeding on longevity in rats, as well as on cardiometabolic health parameters. Twelve-week-old Long-Evans rats were randomized to control or BrSp groups.

Broccoli seeds were sprouted for 4 days then air dried for 7 days before use. Rats were fed 300 mg/kg body weight BrSp 3 days per week (Monday, Wednesday, Friday, to limit rat agitation) beginning at 4 months of age until death/euthanasia.

Mean age at death for the oldest 25% of male rats was higher in BrSp-fed rats (838 ± 18 days) than controls (754 ± 17 days). In females, BrSp feeding improved survival.

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BrSp feeding of rodents starting at 4 months of age caused:

  1. Extended life span in rats, albeit this was observed predominantly in females;
  2. Reduced body weight gain in females;
  3. Modest improvements in glucose handling in males;
  4. Marked blood pressure reduction in males; and
  5. Modest changes in behavioral traits examined at 18 months in both sexes.

These findings highlight sex-dependent benefits of BrSp on improving longevity and delaying cardiometabolic decline associated with aging in rats.”

https://www.mdpi.com/1660-4601/19/20/13468/htm “Broccoli Sprouts Promote Sex-Dependent Cardiometabolic Health and Longevity in Long-Evans Rats”

A human equivalent to this study’s dose is (.162 x 300 mg/kg)  x 70 kg = 3.4 grams dry weight three times a week. Per Drying broccoli sprouts, dried 3-day-old broccoli sprouts contain 10% moisture, and fresh 3-day-old broccoli sprouts contain 82.6% moisture. So 3.4 grams of broccoli sprout powder may be an approximate equivalent of 3.4 g x (.826 / .1) = 28 grams fresh broccoli sprouts.

Not sure why a dose regimen of “(Monday, Wednesday, Friday, to limit rat agitation)” was necessary, as that limited human applicability, lifespan results, and healthspan results. Still, this study was a step forward, and encouraged further lifespan and healthspan studies on broccoli sprout consumption.

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Broccoli leaves and stems vs. highly-processed food

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

This 2022 rodent study investigated whether obesity caused by typical diets could be affected by adding a flour made of broccoli by-products:

“Obesity usually arises as a consequence of an excess of energy intake relative to the expense of energy via metabolic and physical activity. However, combinations of genetic, behavioral, and environmental factors can also contribute to obesity.

Broccoli by-products flour (BF) supplementation helped to maintain a lower body weight, reduced adipose tissue accumulation, and enhanced basal activity of superoxide dismutase and glutathione S-transferase.

treatment groups

  1. CTR – Western diet, control group;
  2. WD – Western diet plus 0.20% cholesterol;
  3. CTR+1.34BF – control diet containing 1.34% BF;
  4. WD+0.67BF – Western diet plus 0.20% cholesterol with 0.67% BF;
  5. WD+1.34BF – Western diet plus 0.20% cholesterol with 1.34% BF;
  6. WD+0.67BF(4w) – Western diet plus 0.20% cholesterol for 10 weeks and then fed with the corresponding diet supplemented with BF at 0.67% for 4 weeks;
  7. WD+1.34BF(4w) – Western diet plus 0.20% cholesterol for 10 weeks and then fed with the corresponding diet supplemented with BF at 1.34% for 4 weeks.

The dose of BF used in testing was established assuming that an adult person of 60 kg consumes around 150 g fresh broccoli per serving, which corresponds to around 19.05 g dry weight according to our laboratory. Consumption of 19.05 g BF per person corresponds to a dose of 317.5 mg/kg. Applying a dose conversion formula between humans (60 kg) and mice (20 g) (25), the equivalent dose will be 3905.25 mg/kg in a mouse, corresponding to around 78 mg BF/mouse.

Assuming that an adult person consumes on average 3 servings of broccoli per week, the intake of 78 mg BF three times a week is equivalent to the intake of 234 mg BF/week/mouse, corresponding to an average daily intake of 33.43 mg BF/mouse. For a mouse with a 5 g average daily food intake, this corresponds to 0.67% (w/w) of the daily feed.

results

Care must be taken with interpreting results obtained from preclinical animal models, as doses and administration protocols are often not comparable between experimental animals and humans. It is difficult to mimic the complexity of human diseases, and effective doses are different due to differences between species. Another limitation is concentrations of beneficial compounds may vary according to different climatic conditions, growing seasons, and cultivars.

BF appears to have a beneficial effect in preventing weight gain and fat accumulation induced by hypercholesterolemic diets.”

https://iv.iiarjournals.org/content/36/5/2173 “Beneficial Effects of Broccoli (Brassica oleracea var italica) By-products in Diet-induced Obese Mice”

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If you were given a lens to see clearly, would you accept it?

gettingwell4 5+ stars Premium, Amygdala, Brainstem, Cerebrum, Cortisol, Epigenetics, Hippocampus, Hypothalamus, Limbic system, Locus coeruleus, Lower brain, Memory, Neurochemicals, Primal Therapy, Serotonin, Stress , , , , , , , ,

Two papers, starting with a 2022 rodent study of maternal behaviors’ effects on offspring physiologies:

“Early life adversity (ELA) is a major risk factor for development of pathology. Predictability of parental care may be a distinguishing feature of different forms of ELA.

We tested the hypothesis that changes in maternal behavior in mice would be contingent on the type of ELA experienced, directly comparing predictability of care in limited bedding and nesting (LBN) and maternal separation (MS) paradigms. We then tested whether predictability of ELA environment altered expression of corticotropin-releasing hormone (Crh), a sexually-dimorphic neuropeptide that regulates threat-related learning.

MS was associated with increased expression of Crh-related genes in males, but not females. LBN primarily increased expression of these genes in females, but not males.”

https://www.sciencedirect.com/science/article/pii/S2352289522000595 “Resource scarcity but not maternal separation provokes unpredictable maternal care sequences in mice and both upregulate Crh-associated gene expression in the amygdala”

I came across this first study by it citing a republished version of 2005 epigenetic research from McGill University:

“Early experience permanently alters behavior and physiology. A critical question concerns the mechanism of these environmental programming effects.

We propose that epigenomic changes serve as an intermediate process that imprints dynamic environmental experiences on the fixed genome, resulting in stable alterations in phenotype. These findings demonstrate that structural modifications of DNA can be established through environmental programming and that – in spite of inherent stability of this epigenomic marker – it is dynamic and potentially reversible.”

https://www.tandfonline.com/doi/full/10.31887/DCNS.2005.7.2/mmeaney “Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome”

This post commemorates the five-year anniversary of Dr. Arthur Janov’s death. Its title is taken from my reaction to his comment on Beyond Belief: Symptoms of hopelessness. Search his blog for mentions of the second paper’s coauthors, Drs. Meaney and Szyf.

Our lives are substantially a product of our parents’ actualized and unsatisfied needs. Our children and their children are reflections of us with our problems (unfelt needs) or elucidations (felt needs).

What if the price we pay for avoiding and pressuring down our feelings is: A wasted life?

What if the grand hypothesis worth proving is: For one’s life to have meaning, each individual has to regain their feelings?

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All about walnuts’ effects

gettingwell4 4-5 stars Advanced knowledge, Acetylcholine, Amygdala, Cerebrum, Epigenetics, Hippocampus, Hypothalamus, Immune system, Limbic system, Memory, Neurochemicals, Stress, Telomeres , , , ,

Five 2022 papers focusing on walnuts, starting with a comparison of eight tree nuts:

“The aim of the present study was to examine 8 different popular nuts – pecan, pine, hazelnuts, pistachio, almonds, cashew, walnuts, and macadamia. Total content of phenolic compounds in nuts ranged from 5.9 (pistachio) to 432.9 (walnuts) mg/100 g.

Walnuts had the highest content of polymeric procyanidins, which are of great interest as important compounds in nutrition and biological activity, as they exhibit antioxidant, anti-inflammatory, antimicrobial, cardio- and neuroprotective action. Walnuts are good sources of fatty acids, especially omega-3 and omega-6.”

https://www.sciencedirect.com/science/article/pii/S2590157522002164 “Nuts as functional foods: Variation of nutritional and phytochemical profiles and their in vitro bioactive properties”

A second study compared the same eight tree nuts plus Brazil nuts and peanuts:

“The highest total content of all analyzed flavonoids was determined in walnuts (114.861 µg/g) with epicatechin the most abundant, while the lowest was in almonds (1.717 µg/g). Epicatechin has antioxidant, anti-inflammatory, antitumor, and anti-diabetic properties. Epicatechin has beneficial effects on the nervous system, enhances muscle performance, and improves cardiac function.”

https://www.mdpi.com/1420-3049/27/14/4326/htm “The Content of Phenolic Compounds and Mineral Elements in Edible Nuts”

Next, two systematic reviews and meta-analyses of human studies:

“We carried out a systematic review of cohort studies and randomized controlled trials (RCTs) investigating walnut consumption, compared with no or lower walnut consumption, including those with subjects from within the general population and those with existing health conditions, published from 2017 to 5 May 2021.

  • Evidence published since 2017 is consistent with previous research suggesting that walnut consumption improves lipid profiles and is associated with reduced CVD risk.
  • Evidence pointing to effects on blood pressure, inflammation, hemostatic markers, and glucose metabolism remains conflicting.
  • Evidence from human studies showing that walnut consumption may benefit cognitive health, which is needed to corroborate findings from animal studies, is now beginning to accumulate.”

https://academic.oup.com/nutritionreviews/advance-article/doi/10.1093/nutrit/nuac040/6651942 “Walnut consumption and health outcomes with public health relevance – a systematic review of cohort studies and randomized controlled trials published from 2017 to present”

“We aimed to perform a systematic review and meta-analysis of RCTs to thoroughly assess data concerning effects of walnut intake on selected markers of inflammation and metabolic syndrome in mature adults. Our findings showed that:

  • Walnut-enriched diets significantly decreased TG, TC, and LDL-C concentrations, while HDL-C levels were not significantly affected.
  • No significant changes were noticed on anthropometric, cardiometabolic, and glycemic indices after higher walnut consumption.
  • Inflammatory biomarkers did not record statistically significant results.”

https://www.mdpi.com/2076-3921/11/7/1412/htm “Walnut Intake Interventions Targeting Biomarkers of Metabolic Syndrome and Inflammation in Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials”

Finishing with a rodent study that gave subjects diabetes with a high-fat diet, then mixed two concentrations of walnut extract in with the treatment groups’ chow:

“This study was conducted to evaluate the protective effect of Gimcheon 1ho cultivar walnut (GC) on cerebral disorder by insulin resistance, oxidative stress, and inflammation in HFD-induced diabetic disorder mice. After HFD feed was supplied for 12 weeks, samples were orally ingested for 4 weeks to GC20 and GC50 groups (20 and 50 mg/kg of body weight, respectively).

  • Administration of GC improved mitochondrial membrane potential function, and suppressed oxidative stress in the brain.
  • GC inhibited hepatic and cerebral lipid peroxidation and the formation of serum AGEs, and increased serum antioxidant activity to improve HFD-induced oxidative stress.
  • The HFD group showed significant memory impairment in behavioral tests. On the other hand, administration of GC showed improvement in spatial learning and memory function.

walnut brain effects

Based on these physiological activities, GC showed protective effects against HFD-induced diabetic dysfunctions through complex and diverse pathways.”

https://www.mdpi.com/1420-3049/27/16/5316/htm “Walnut Prevents Cognitive Impairment by Regulating the Synaptic and Mitochondrial Dysfunction via JNK Signaling and Apoptosis Pathway in High-Fat Diet-Induced C57BL/6 Mice”

How do you like my sand art?PXL_20221016_154923750

Measuring epigenetic DNA causes

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

This 2022 human cell study investigated DNA methylation and aging:

“Models based on DNA methylation can be used to predict the age of biological samples, but their interpretability is limited due to the lack of causal inferences. Neither existing epigenetic clocks nor DNA methylation changes are enriched in causal CpG sites. Causal CpGs include similar numbers of sites that contribute to aging and protect against it, yet their combined contribution negatively affects age-related traits.

One general approach for developing anti-aging interventions is to identify molecular changes during aging and use these changes as targets to modulate the aging process. A similar idea has also been applied to evaluate potential longevity interventions. However, this logic is intrinsically flawed, as correlation does not imply causation, and age-related changes are not necessarily causal to age-associated declines.

We developed a framework for integrating causal knowledge into epigenetic clock models and constructed DamAge and AdaptAge that measure age-related damaging and adaptive changes, respectively. DamAge acceleration is associated with various adverse conditions (e.g., mortality risk), whereas AdaptAge acceleration is related to beneficial adaptations.

causality clocks

We found that transcription factor (TF)-binding sites of BRD4 and CREB1 are enriched with CpG sites whose methylation levels promote healthy longevity, and TF-binding sites for HDAC1 are enriched with CpG sites whose methylation levels decrease healthy longevity.

  • BRD4 contributes to cell senescence and promotes inflammation, and higher DNA methylation at BRD4 binding sites may inhibit the downstream effects of BRD4 and promote healthy longevity.
  • CREB1 is related to type II diabetes and neurodegeneration, and mediates the effect of calorie restriction. Our data suggest that higher methylation at CREB1-binding sites may support its longevity effects.
  • HDAC1 is a histone deacetylase, and its activity increases with aging and may promote age-related phenotypes. Increased DNA methylation at HDAC1 binding sites may causally inhibit healthy longevity.

Our causality-informed clock models provide novel insights into the aging mechanisms and testing interventions that delay aging and reverse biological age.”

https://www.biorxiv.org/content/10.1101/2022.10.07.511382v1 “Causal Epigenetic Age Uncouples Damage and Adaptation”

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Eat broccoli sprouts to combat effects of BPA?

gettingwell4 2-3 stars Required further work, Epigenetics ,

This 2022 rodent study investigated abilities of both glucoraphanin and sulforaphane to reduce bisphenol A’s effects:

“There are only a few studies on the anti-obesogenic activity of sulforaphane (SFN) in bisphenol A (BPA)-induced obese C57BL/6J mice and 3T3-L1 cells. BPA is one of the endocrine disrupting chemicals that mimics bioidentical hormones and acts as an active agonist of glucocorticoid receptors to promote adipogenesis.

We investigated anti-obesogenic effects of broccoli sprouts powder (BSP) with a high glucoraphanin (GRA) content, mustard (Sinapis alba L.) seed powder (MSP) that has a high myrosinase activity, and sulforaphane-rich MSP-BSP mixture powder (MBP).

  • GRA content in BSP was 131.11 ± 1.84 μmol/g, and SFN was not detected.
  • SFN content in MBP was 162.29 ± 1.24 μmol/g, and GRA was not detected.
  • GRA and SFN were not detected in MSP.

Mice were administered:

  • BPA (500 μg/kg/day);
  • BPA supplemented with 100 mg/kg/day Gar (BPA + Gar);
  • 15 mg/kg/day MSP (BPA + MSP);
  • 150 mg/kg/day BSP (BPA + BSP); or
  • 100 mg/kg/day MBP (BPA + MBP)

for 12 weeks. The BPA + Gar group served as the positive control group, since studies showed that Garcinia cambogia extract induces weight loss.

bpa weight gain

Mice in the BPA group showed a significantly high body weight and epididymal adipose tissue weight, compared to the ND group mice. MSP treatment had no significant effects. Gar, BSP, and MBP treatment significantly decreased body weight and epididymal adipose tissue weight in BPA-induced obese mice.

BSP and MBP exert anti-obesogenic effects by activating the AMPK signaling pathway. Our results suggest that BSP and MBP could be effective in the treatment and prevention of BPA-induced obesity.”

https://www.mdpi.com/2072-6643/14/18/3814/htm “Anti-Obesogenic Effects of Sulforaphane-Rich Broccoli (Brassica oleracea var. italica) Sprouts and Myrosinase-Rich Mustard (Sinapis alba L.) Seeds In Vitro and In Vivo”

Human daily equivalent doses:

  • Sulforaphane was (.081 * 100 mg) x 70 kg = 567 mg, or (.567 g * 162.29 μmol/g) = 92 μmol. The μmol amount is reasonable, but the mg weight would be intolerable. I’ve contacted these researchers for clarification, and will update with their response.
  • Glucoraphanin in broccoli sprout powder at (.081 * 150 mg) x 70 kg = 851 mg looks reasonable. Broccoli sprout powder vendors recommend 1 gram.

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