Genetic factors

How will you feel?

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Consider this a partial repost of Moral Fiber:

“We are all self-reproducing bioreactors. We provide an environment for trillions of microbes, most of which cannot survive for long without the food, shelter and a place to breed that we provide.

They inhabit us so thoroughly that not a single tissue in our body is sterile. Our microbiome affects our development, character, mood and health, and we affect it via our diet, medications and mood states.

The microbiome:

  • Affects our thinking and our mood;
  • Influences how we develop;
  • Molds our personalities;
  • Our sociability;
  • Our responses to fear and pain;
  • Our proneness to brain disease; and
  • May be as or more important in these respects than our genetic makeup.

Dysbiosis has become prevalent due to removal of prebiotic fibers from today’s ultra-processed foods. I believe that dietary shift has created a generation of humans less able to sustain or receive love.

They suffer from reduced motivation and lower impulse control. They are more anxious, more depressed, more selfish, more polarized, and therefore more susceptible to the corrosive politics of identity.“

Other recent blog posts by Dr. Paul Clayton and team include Skin in The Game and Kenosha Kids.

Image from Thomas Cole : The Consummation, The Course of the Empire (1836) Canvas Gallery Wrapped Giclee Wall Art Print (D4060)

Problematic rodent sulforaphane studies

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I was asked to give an example of Human relevance of rodent sulforaphane studies. I’ll use the 2020 Sulforaphane Diminishes the Formation of Mammary Tumors in Rats Exposed to 17β-Estradiol.

1. This study’s sulforaphane dose was “100 μmol/kg SFN..gavage regimen on Monday, Wednesday and Friday for 56 weeks.” From the October 2019 Broccoli or Sulforaphane: Is It the Source or Dose That Matters? “Allometric scaling uses the correction factor for rat doses 0.162” and this graphic:

Interpreting the human-relevant range:

Interpreting that 8% of the rodent studies were clinically relevant to human sulforaphane doses as a lower boundary (1.43 µmol / kg) and tolerable to humans as an upper boundary (4 µmol / kg):

A human equivalent of this study’s dose is (100 μmol/kg x .162) = 16.2 µmol / kg. See the original blog post for a study showing that a majority of both treatment and control group subjects will refuse and stop with sulforaphane doses less than half of this study’s human equivalent.

2. From Week 28, “The maximum lifespan for rats and humans were set to 3.8 years and 122.5 years, respectively.” A human-equivalent multiplication factor that can be applied to a rat post-development time period is 122.5 / 3.8 = 32.2.

Assuming this study’s subjects could achieve maximum lifespan, a human equivalent of 56 weeks is (56 x 32.2) ≈ 1,803 weeks, or ≈ 34.7 years.

3. Let’s assert that the main purpose of animal studies is to help humans.

Was it possible for this study to achieve this goal when it used intolerable human-equivalent sulforaphane doses for a period equivalent to over three decades of our lives?

Yet its Discussion section proposed that it’s useful for human guidance on:

  • Obesity;
  • Breast cancer in premenopausal and postmenopausal women;
  • Hormone status;
  • Phospholipids for cellular health and homeostasis;
  • Serum free fatty acids and triglycerides; and
  • Lipid metabolism and DNA damage.

4. These researchers definitely knew what this study was going to do. A coauthor of the above referenced 2019 paper was also a coauthor of this study, who “conceived the original study design and supervised the project.”

Why did they do it? The coauthor’s shared apology – published in the October 2019 paper – for these types of studies was:

“Animal studies have not delivered all that might be expected of them. Pre-clinical experimentalists have not thought carefully about the selection of dose (or route) and its relevance to clinical utility.

Authors of this review have contributed to this dose skewing.”

This study was published in July 2020.

It wasn’t just a waste of resources. It detracted from science because people won’t recognize that its findings are inapplicable to humans.

Part 2 of Switch on your Nrf2 signaling pathway

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To follow up topics of Part 1‘s interview:

1. “We each have a unique microbial signature in the gut. Metabolites that you produce might not be the same ones that I produce. This makes clinical studies very difficult because you don’t have a level playing field.”

This description of inter-individual variability could inform researchers’ investigations prior to receiving experimental results such as:

Post-experimental analysis with statistical packages of these types of results is required. But it doesn’t produce meaningful explanations for such individual effects.

Analysis of individual differences in metabolism can better inform explanations, because it would investigate causes for widely-variable effects. Better predictive hypotheses could be a result.

2. Today I’m starting my 40th week of eating a clinically-relevant amount of microwaved 3-day-old broccoli sprouts every day. To encourage sulforaphane’s main effect of Nrf2 signaling pathway activation, I won’t combine broccoli sprouts with anything else either during or an hour before or after.

I had been taking supplements at the same time. This interview got me thinking about the 616,645 possible combinations of my 19 supplements and broccoli sprouts.

That’s way too many to be adequately investigated by humans. Especially because contexts for each combination’s synergistic, antagonistic, or additive activities may be influenced by other combinations’ results.

I’ll just eat food and take supplements outside of this sulforaphane window.

I’ve taken 750 mg fructo-oligosaccharides (FOS) twice a day for sixteen years. I’ve considered it as my only prebiotic. Hadn’t thought of either of these points:

  • “Polyphenols are now considered to be a prebiotic food for microflora in the gut. They tend to focus on producing additional amounts of lesser known species like Akkermansia muciniphila, and have a direct prebiotic effect. Microbiota break these big, bulky molecules down into smaller metabolites, which clearly are absorbed. Some beneficial effects that come from polyphenols are not from the original molecule itself, but from a variety of metabolites produced in the gut.
  • We use a prebiotic, actually called an immunobiotic, which is a dead lactobacillus plantarum cell optimised for its cell wall content of lipoteichoic acid. Lipoteichoic acid attaches to toll-like receptor 2, and that sets off a whole host of immune-modulating processes, which tend to enhance infection control and downregulate inflammation and downregulate allergenicity.”

3. “Quinone reductase is critical because it is the final enzyme in the phase two detox pathway that stops DNA being mutated or prevents deformation of DNA adducts which are mutagenic. I want to look at genes that govern redox balance, inflammation, detoxification processes, cellular energetics, and methylation.”

Gene functional group classifications are apparently required in studies, to accompany meaningless statistics. When I’ve read papers attaching significance to gene functional groups, it often seemed like hypothesis-seeking efforts to overcome limited findings.

I’ll start looking closer when study findings include Nrf2 signaling pathway targets quinone reductase, DNA damage marker 8-hydroxydeoxyguanosine, and enzymes glutathione peroxidase and glutathione S-transferase.

4. I bolded “unregulated inflammation” in Part 1 because it’s a phrase I’d ask to be defined if that site enabled comments. Thinking on inflammation seems to come from:

“We focus on the intestinal epithelial cell as a key player because if you enhance function of that cell, and Nrf2 is part of that story, once you get those cells working as they should, they are modulating this whole underlying immune network.”

An environmental signaling paradigm of aging and Reevaluate findings in another paradigm have a different focus. That paradigm looks at inflammation in the context of aging:

“A link between inflammation and aging is the finding that inflammatory and stress responses activate NF-κB in the hypothalamus and induce a signaling pathway that reduces production of gonadotropin-releasing hormone (GnRH) by neurons.

The case is particularly interesting when we realize that the aging phenotype can only be maintained by continuous activation of NF-κB. So here we have a multi-level interaction:

  1. Activation of NF-κB leads to
  2. Cellular aging, leading to
  3. Diminished production of GnRH, which then
  4. Acts (through cells with a receptor for it, or indirectly as a result of changes to GnRH-receptor-possessing cells) to decrease lifespan.

Cell energetics is not the solution, and will never lead to a solution because it makes the assumption that cells age. Cells take on the age-phenotype the body gives them.

Aging is not a defect – it’s a programmed progressive process, a continuation of development with the body doing more to kill itself with advancing years. Progressive life-states where each succeeding life-stage has a higher mortality (there are rare exceptions).

Cellular aging is externally controlled (cell non-autonomous). None of those remedies that slow ‘cell aging’ (basically all anti-aging medicines) can significantly extend anything but old age.

For change at the epigenomic/cellular level to travel up the biological hierarchy from cells to organ systems seems to take time. But the process can be repeated indefinitely (so far as we know).”

Switch on your Nrf2 signaling pathway

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An informative interview to start this year with the author of Sulforaphane: Its “Coming of Age” as a Clinically Relevant Nutraceutical in the Prevention and Treatment of Chronic Disease:

The Antioxidant Dilemma with Dr. Christine Houghton

“The thing about science is, the more you know, the more you realise you don’t know. And I have this enormous respect now for signalling processes that are going on within the cell, and not just signalling. The way mother nature switches on, switches off, foot on brake, foot on accelerator, continuously all of the time.

Things have changed in understanding the function of Nrf2 for a start, in controlling in many ways those cellular defences. We could then switch on Nrf2. You switch on a whole host of protective molecules all at the same time.

We use NAC [N-acetyl-cysteine] in the lab all the time because it stops an Nrf2 activation. So, that weak pro-oxidant signal that you use to activate 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.

The real advantage of sulforaphane is not only is it the most potent inducer of Nrf2, or activator, but it’s also highly bioavailable. It’s a very tiny, low-molecular weight, lipophilic molecule that just glides straight in through cell membranes. It’s about 80% bioavailable. Whereas big, bulky polyphenols are about 1% bioavailable just simply because of their chemical structure.

We focus on the intestinal epithelial cell as a key player because if you enhance function of that cell, and Nrf2 is part of that story, once you get those cells working as they should, they are modulating this whole underlying immune network.

I’m particularly interested in looking at core upstream factors that govern cellular defences. So, I want to look at genes that govern redox balance, inflammation, detoxification processes, cellular energetics, and methylation.

Intestinal epithelial, just like any other cell in the body, will respond to Nrf2 activation. It will respond to NF-κB downregulation. That’s going to enhance redox control. It’s going to reduce unregulated inflammation. It’s going to enhance detoxification processes. It’ll increase glutathione synthesis.

All of those core factors that any cell needs to work normally will be enhanced by activating Nrf2. And I use a high-yielding sulforaphane supplement of about 20 milligrams a day to do that. So, that’s the beginning.

Probiotics don’t typically colonise in an adult. That’s where we come back to this idea of restoring the gut ecosystem and using prebiotic foods.

In an ideal world, we’d be looking at 600 to 800 grams of non-starchy plant foods a day. In a real world, that isn’t always going to happen.

I never use the term leaky gut because it isn’t that. It’s a dynamic structure that becomes unresponsive.”

Hadn’t thought about weighing my daily AGE-less Chicken Vegetable Soup dinner (half) then tomorrow for lunch. Its total weight tonight was 2,575.5 grams.

  • Subtract 207.2 g wine, 985.6 g chicken broth, and 64.2 g noodles;
  • Add 131 g 3-day-old broccoli sprouts microwaved to ≤ 60°C (140°F) eaten earlier;
  • Subtract an estimated 170 g (6 oz.) chicken, didn’t measure juice squeezed from one lemon, didn’t estimate evaporation from 20 minutes cooking; and
  • Didn’t include either 81 g dry weight steel-cut oats which becomes 308 g for breakfast, or 103.8 g 3-day-old hulled oat sprouts.
  • Net 1,279.5 grams non-starchy plant foods

I’m doing alright by the “600 to 800 grams of non-starchy plant foods a day” guideline. Should exercise more, though, because I eat a lot.

Topics continued in Part 2.

A case for carnitine supplementation

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This 2020 review subject was carnitine, acetyl-L-carnitine, and its other molecular forms:

“Carnitine is necessary to deliver long-chain fatty acids from cytosol into mitochondria. Carnitine homeostasis is maintained by diet and renal absorption, as only a small amount (about 25%) is obtained by endogenous biosynthesis.

Defective fatty acid oxidation occurs with reduced intracellular levels of carnitine, leading to glucose consumption instead of lipid consumption, resulting in hypoglycemia. Non-metabolized lipids accumulate in tissues such as heart, skeletal muscle, and liver, resulting in myopathy and hepatic steatosis.

2000 mg/day is unlikely to provoke unwanted side effects and is safe for humans. In-depth studies are needed to identify a unique method of analysis which can guarantee efficient monitoring of supplement active component amounts.”

https://www.mdpi.com/1420-3049/25/9/2127/htm “The Nutraceutical Value of Carnitine and Its Use in Dietary Supplements”

The review listed animal studies of L-carnitine alone and in combination with:

  • Vitamin D3;
  • Coenzyme Q10;
  • Nicotinamide riboside;
  • Selenium;
  • L-arginine;
  • Anti-histamine drugs cetirizine hydrochloride and chlorpheniramine maleate; and
  • Hypertension drug olmesartan.

Human studies of its effects included:

  • Muscle soreness, damage biomarkers, and cramps;
  • Osteoarthritis knee pain and inflammation markers;
  • Ischemic cerebrovascular injury;
  • Peripheral neuropathy;
  • Nonalcoholic fatty liver disease;
  • Insulin resistance and Type 2 diabetes;
  • Kidney diseases;
  • Inherited diseases phenylketonuria and maple syrup urine;
  • Stress, depression, and anxiety;
  • Male infertility; and
  • Hepatitis C.

Sprouting hulled oats

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My Sprouting whole oats trial was a hassle with hulls and a poor germination rate. This week I used hulled oat seeds from a different vendor, and a different study, Degree of oat sprouting, as my model.

  • Oat variety of Avena sativa was a small seed, 7 mm x 2 mm. The model used “huskless oat ‘Gehl'” which is a different species (Avena nuda).
  • 100 seeds weighed 1.5 grams. There were over 1,300 seeds per 20 g batches.
  • Oat sprout batches were processed the same way I do broccoli sprout batches. A new batch started soaking to start germination every 12 hours, then was rinsed three times every 24 hours on a 6 hours – 6 hours – 12 hours cycle. I have an open question to the model’s corresponding coauthor to explain their “4.5‐hr wet steeping, 19‐hr air rest, and 4‐hr steeping, all at 20°C” procedures to start germination, since I didn’t have access to its cited study. The model grew oat sprouts for 1, 2, and 3 days.
  • Temperature in my kitchen was 21°C (70°F) because it’s winter outside. The model grew oat sprouts at 10, 14, 20, 25, and 30°C. Their findings included “Temperatures between 20° and 25°C yielded the most dramatic changes in properties of sprouted oats.”

I evaluated germination results per the model’s Degree of Sprouting finding:

“Length of the coleoptile [shoot] was selected as a criterion of categorization of degree of sprouting. Grains of degree 0 do not show any radicle [root] or coleoptile growth. Degree:

  1. Has visible embryos (small white point), while radicles and coleoptile are not visible;
  2. Shows a developed embryo emerging from the seed coat;
  3. Coleoptile lengths of at least half the oat grain length;
  4. Coleoptile lengths between half and a full grain length; and
  5. Coleoptile longer than a full grain length.”

Most of this trial wasn’t a big deal, adding just a few extra minutes onto what I do three times a day with broccoli sprouts. Here’s what this oat variety’s hulled seeds and 3-day-old sprouts looked like:

The tedious part was evaluating degrees of sprouting. I took as large a bottom-to-top sample as I could tolerate sorting (235 seeds / sprouts, about 17%), with these results:

A 97% germination rate. 🙂 Average weight of three 3-day-old batches was 51.9 grams, for a 260% weight gain. My 5-day-old whole oat sprouts trial had a 22% germination rate and a 221% weight gain.

The model’s Figure 3 Degree of Sprouting finding for 20°C and 25°C at 3 days was hard to read:

Don’t know how > 1% 0 degrees of sprouting at 20°C and 25°C reconciled with their statement “Germinability after 3 days was about 99% at all temperatures.” A numerical table wasn’t provided – yet another question for the corresponding author. Meanwhile, I’ll estimate:

Their hard-to-read Figure 3 also wasn’t completely congruent with their statement:

“Around 20% of grains sprouted at 20° and 25°C had a coleoptile longer than a full grain length (degree of sprouting 5).”

These oat sprouts tasted milder than my previous trial’s. With more than a third at a degree-of-sprouting 5 measurement, they’re sweet, concurrent with the model’s findings that:

“Increased amounts of reducing sugars and ascorbic acid were found particularly in the radicles and coleoptile. Coleoptile and radicle growth (input parameters for the degree of sprouting) and reducing sugars and α‐amylase activity are interdependent.”

Corresponding increased enzyme concentrations produced an aftertaste, though. I ate them along with either food or drink.

Can eating three-day-old oat sprouts of this Montana cultivated variety help with what I’m already doing? Here’s what I expect, given the model was a different oat species, and the Sprouting oats and Oat sprouts analysis studies used different oat cultivars.

1. In order of magnitude: increased antioxidants, GABA, phenolic compounds, protein, amino acids, β-glucan, and polyunsaturated fatty acids. Don’t know about GABA and protein, but the others may help counter inflammation.

2. Increased enzyme intake. The model study used α-amylase as a marker for α-amylase enzymes (catalyze starches), protease enzymes (catalyze proteins), and lipase enzymes (catalyze fats).

Oat sprouts analysis characterized increased α-amylase and lipase activities as undesirable in a sprouted oat flour context. More on enzymes in Part 2 of Sprouting hulled oats.

Week 37 of Changing to a youthful phenotype with broccoli sprouts

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1. Been wrong about a few things this past week:

A. I thought in Week 28 that extrapolating A rejuvenation therapy and sulforaphane results to humans would produce personal results by this week. An 8-day rat treatment period ≈ 258 human days, and 258 / 7 ≈ 37 weeks.

There are just too many unknowns to say why that didn’t happen. So I’ll patiently continue eating a clinically relevant 65.5 gram dose of microwaved broccoli sprouts twice every day.

PXL_20201015_105645362

The study’s lead researcher answered:

“Depends, it might take 37 weeks or more for some aspects of ‘youthening’ to become obvious. It might even take years for others.

Who really cares if you are growing younger every day?

For change at the epigenomic/cellular level to travel up the biological hierarchy from cells to organ systems seems to take time. But the process can be repeated indefinitely (so far as we know) so by the second rejuvenation you’re already starting at ‘young’. (That would be every eight to ten years I believe.)”

His framework is in An environmental signaling paradigm of aging.

B. I thought that adding 2% mustard seed powder to microwaved broccoli sprouts per Does sulforaphane reach the colon? would work. Maybe it would, maybe it wouldn’t, but my stomach and gut said that wasn’t for me.

C. I thought I could easily add Sprouting whole oats to my routine. I ran another trial Sprouting hulled oats using oat seeds from a different company and Degree of oat sprouting as a model.

2. Oat sprouts analysis paired studies were very informative, don’t you think? One study produced evidence over 18 germination-parameter combinations (hulled / dehulled seeds of two varieties, for 1-to-9 days, at 12-to-20°C).

Those researchers evaluated what mix of germination parameters would simultaneously maximize four parameters (β-glucan, free phenolic compounds, protease activity, and antioxidant capacity) while minimizing two (enzymes α-amylase and lipase). Then they followed with a study that characterized oat seeds sprouted under these optimal conditions.

I doubted PubMed’s “oat sprout” 20 search results for research 1977 to the present. Don’t know why they didn’t pick up both of these 2020 studies, but I’m sure that .gov obvious hindrances to obtaining relevant information like this won’t be fixed. What other search terms won’t return adequate PubMed results?

3. The blog post readers viewed this week that I made even better was Do delusions have therapeutic value? from May 2019. Sometimes I’ve done good posts describing why papers are poorly researched.

4. I’ve often changed my Week 4 recipe for an AGE-less Chicken Vegetable Soup dinner (half) then the next day for lunch. The biggest change brought about by 33 weeks of behavioral contagion is that I now care more about whether vegetables are available than whether or not they’re organic. Coincidentally, I’ve developed a Costco addiction that may require intervention.

  • 1/2 lemon
  • 4 Roma tomatoes
  • 4 large carrots
  • 6 stalks organic celery
  • 6 mushrooms
  • 6 cloves garlic
  • 6 oz. organic chicken breast fillet
  • 1 yellow squash, alternated with 1 zucchini
  • 1 cup sauvignon blanc
  • 32 oz. “unsalted” chicken broth, which still contains 24% of the sodium RDA

Pour wine into a 6-quart Instant Pot; cut and strain squeezed lemon; cut chicken into 1/4″ cubes and add; start mixture on Sauté. Wash and cut celery and stir in. Wash and cut carrots and stir in.

When pot boils around 8 minutes, add chicken broth and stir. Wash mushrooms, slicing into spoon sizes.

Wash and slice yellow squash / zucchini. Crush and peel garlic, tear but don’t slice. Turn off pot when it boils again around 15 minutes.

Wait 2-3 minutes for boiling to subside, then add yellow squash / zucchini, mushrooms, garlic, whole tomatoes. Let set for 20 minutes; stir bottom-to-top 5 and 15 minutes after turning off, and again before serving.

AGE-less Chicken Vegetable Soup is tasty enough to not need seasoning.

Oat sprouts analysis

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A research group published two 2020 studies on sprouting oat seeds. Their first study produced evidence over a range of germination parameters (hulled / dehulled seeds of two varieties, for 1-to-9 days, at 12-to-20°C):

“The aim was to investigate the influence of germination period and temperature on protein profile, bioactive potential (β-glucan and phenolic contents), antioxidant capacity, and on activity of enzymes (α-amylase, protease and lipase) from hulled and dehulled oat varieties. Multi-response optimization was used to identify optimal germination conditions that maximize sprouted oat flour quality.

  • Hulled (variety Barra) and dehulled (variety Meeri) germination was performed in dark at different temperatures (12, 14, 16, 18, and 20 ◦C) and duration (24, 60, 96, 156, and 216 h).
  • Germination at 16 ◦C for 216 h and 20 ◦C for 96 h produced the highest protein accumulation in varieties Barra and Meeri, respectively.
  • Germination for short periods (24–96 h) combined with medium temperatures (12–16 ◦C) retained β-glucan levels, but longer germination times (156–216 h) caused reductions of 47–64%. Endogenous β-glucanases increase activity during germination, causing hydrolysis of β-glucan.
  • Free phenolic compound content was between 1.6-fold and 2.8-fold higher when germination took place at high temperatures (16–18 ◦C) for longer times.
  • Antioxidant capacity was between 1.4 and 4.5-fold higher. High temperatures (16–18 ◦C) and longer germination times (156–216 h) positively influenced antioxidant capacity.

The effect of germination conditions strongly depended on genetic diversity and presence/absence of hull.

Optimal germination conditions maximize contents of β-glucan, free phenolic compounds, protease activity, and antioxidant capacity, and minimize activity of undesirable enzymes α-amylase and lipase. For variety Meeri, that corresponded to 18 ◦C and time 120 h.”

https://www.sciencedirect.com/science/article/abs/pii/S0023643820309440 “Changes in protein profile, bioactive potential and enzymatic activities of gluten-free flours obtained from hulled and dehulled oat varieties as affected by germination conditions” (not freely available)

Their second 2020 study analyzed properties of 4-day-old oat sprouts. Dehulled oat seeds (variety Meeri) were soaked at room temperature for 4 hours, then germinated in darkness at 18°C with humidity ≥ 90%.

“Sprouted oat powder was an excellent source of protein (10.7%), β-glucan (2.1%), thiamine, riboflavin, and minerals (P, K, Mg and Ca). It presented better amino acid and fatty acid compositions, and levels of γ-aminobutyric acid [GABA], free phenolics, and antioxidant capacity than control.

Protein content (g/100 g) and amino acid profile (g/100 g protein). Different letters within a row indicate p ≤ 0.05 statistical differences.

During germination, proteins are partially hydrolyzed increasing availability of free amino acids. Activity of glutamate decarboxylase enzyme is enhanced.

However, no significant reduction of glutamate content was observed. Glutamate is used for GABA and protein synthesis, but it is also produced by protein hydrolysis, glutamine synthetase-glutamate synthase cycle, and GABA transaminase reactions.

Sprouted oat powder exhibited 2.5-fold higher SPC [soluble (free) phenolic compounds] levels. De novo synthesis of phenolic compounds or liberation of phenolic compounds that are linked to macromolecules due to cell wall dismantling during germination could explain enhancement of SPC.

Sprouted oat powder displayed a 3-fold higher antioxidant capacity. Release of bound phenolic compounds and de novo synthesis of avenanthramides might be responsible.

Hydrolysis of β-glucan might also cause an increase in oxygen radical absorbance capacity. β-glucan oligosaccharides exhibit high radical scavenging activity and reducing power, and that could be related with exposure of their active hydroxyl groups and decrease of intermolecular hydrogen bonding during germination.”

https://www.sciencedirect.com/science/article/abs/pii/S0308814620318343 “Sprouted oat as a potential gluten-free ingredient with enhanced nutritional and bioactive properties” (not freely available)

Both studies started germination by:

“Twenty grams of oat seeds were used for germination. Soaking (1:6 ratio, w/v) was performed at room temperature (20 ◦C ±2 ◦C) for 4 h.”

Neither study included estimates of germination rates. I contacted the corresponding coauthor for that information, and they replied:

“The germination rate in hulled oat varieties was around 95% and in
dehulled one around 55-70% depending on the germination conditions.”

A broccoli sprouts study that lacked evidence for human applicability

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A 2020 study Combined Broccoli Sprouts and Green Tea Polyphenols Contribute to the Prevention of Estrogen Receptor–Negative Mammary Cancer via Cell Cycle Arrest and Inducing Apoptosis in HER2/neu Mice (not freely available) conclusion was:

“Lifelong BSp [broccoli sprouts] and GTP [green tea polyphenol] administration can prevent estrogen receptor–negative mammary tumorigenesis through cell cycle arrest and inducing apoptosis in HER2/neu mice.”

These researchers had unaddressed insufficiencies in this study that were also in their 2018 study as curated below. The largest item that required translation into human applicability was rodent diet content of 26% “broccoli sprout seeds.”

You may be surprised to read the below previous study’s unevidenced advice to eat double the weight of broccoli sprouts that I eat every day. You won’t be surprised that it’s not going to happen. Especially when no alternatives were presented because rodent diet details weren’t analyzed and published.

Sulforaphane is an evolved defense mechanism to ward off predators, and eating it is evolutionarily unpleasant. Will people in general and pregnant women in particular eat a diet equivalent to 26% “broccoli sprout seeds?”

Where were peer reviewer comments and researcher responses? Are these not public as they are by all Open Access journals hosted on https://www.mdpi.com/?

Sponsors and researchers become locked into paradigms that permit human-inapplicable animal research year after year. What keeps them from developing sufficient human-applicable evidence to support their hypotheses?

This 2018 Alabama rodent study investigated the epigenetic effects on developing breast cancer of timing a sulforaphane-based broccoli sprouts diet. Timing of the diet was as follows:

  1. Conception through weaning (postnatal day 28), named the Prenatal/maternal BSp (broccoli sprouts) treatment (what the mothers ate starting when they were adults at 12 weeks until their pups were weaned; the pups were never on a broccoli sprouts diet);
  2. Postnatal day 28 through the termination of the experiment, named the Postnatal early-life BSp treatment (what the offspring ate starting at 4 weeks; the mothers were never on a broccoli sprouts diet); and
  3. Postnatal day 56 through the termination of the experiment, named the Postnatal adult BSp treatment (what the offspring ate starting when they were adults at 8 weeks; the mothers were never on a broccoli sprouts diet).

“The experiment was terminated when the mean tumor diameter in the control mice exceeded 1.0 cm.

Our study indicates a prenatal/maternal BSp dietary treatment exhibited maximal preventive effects in inhibiting breast cancer development compared to postnatal early-life and adult BSp treatments in two transgenic mouse models that can develop breast cancer.

Postnatal early-life BSp treatment starting prior to puberty onset showed protective effects in prevention of breast cancer but was not as effective as the prenatal/maternal BSp treatment. However, adulthood-administered BSp diet did not reduce mammary tumorigenesis.

The prenatal/maternal BSp diet may:

  • Primarily influence histone modification processes rather than DNA methylation processes that may contribute to its early breast cancer prevention effects;
  • Exert its transplacental breast cancer chemoprevention effects through enhanced histone acetylation activator markers due to reduced HDAC1 expression and enzymatic activity.

This may be also due to the importance of a dietary intervention window that occurs during a critical oncogenic transition period, which is in early life for these two tested transgenic mouse models. Determination of a critical oncogenic transition period could be complicated in humans, which may partially explain the controversial findings of the adult BSp treatment on breast cancer development in the tested mouse models as compared the previous studies. Thus long-term consumption of BSp diet is recommended to prevent cancers in humans.”

“The dietary concentration for BSp used in the mouse studies was 26% BSp in formulated diet, which is equivalent to 266 g (~4 cups) BSp/per day for human consumption. The concentration of BSp in this diet is physiological available and represents a practical consumption level in the human diet.

Prior to the experiment, we tested the potential influences of this prenatal/maternal BSp regimen on maternal and offspring health as well as mammary gland development in the offspring. Our results showed there was no negative effect of this dietary regimen on the above mentioned factors (data not shown) suggesting this diet is safe to use during pregnancy.”

I didn’t see where the above-labelled “Broccoli Sprout Seeds” diet content was defined. It’s one thing to state:

“SFN as the most abundant and bioactive compound in the BSp diet has been identified as a potent HDAC inhibitor that preferably influences histone acetylation processes.”

and describe how sulforaphane may do this and may do that, and include it in the study’s title. It’s another thing to quantify an animal study into findings that can help humans.

The study’s food manufacturer offers dietary products to the public without quantifying all contents. Good for them if they can stay in business by serving customers who can’t be bothered with scientific evidence.

Any difference between the above-labelled “Broccoli Sprout Seeds” and broccoli seeds? Where was any evidence that “Broccoli Sprout Seeds” and SPROUTED “Broccoli Sprout Seeds” were equivalent per this claim:

“Equivalent to 266 g (~4 cups) BSp/per day for human consumption. The concentration of BSp in this diet is physiological available and represents a practical consumption level in the human diet.”

To help humans, this animal study had to have more details than the food manufacturer provided. These researchers should have either tasked the manufacturer to specify “Broccoli Sprout Seeds” content, or contracted out analysis if they weren’t going to do it themselves.

Regarding timing of a broccoli sprouts diet for humans, this study didn’t provide evidence for recommending:

“Long-term consumption of BSp diet is recommended to prevent cancers in humans.”

http://cancerpreventionresearch.aacrjournals.org/content/early/2018/05/15/1940-6207.CAPR-17-0423.full-text.pdf “Temporal efficacy of a sulforaphane-based broccoli sprout diet in prevention of breast cancer through modulation of epigenetic mechanisms”

Sprouting oats

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Three 2020 studies investigated properties of sprouted oats. This first study compared one oat cultivar’s seed and sprout contents for phenolic compounds, and evaluated oat sprouts’ protection against developing colon cancer:

“The purpose of this investigation was to evaluate whether sprouted oats (SO) of the Turquesa variety still possessed effective physiologically bioactive compounds, i.e., phenolics, flavonoids, AVAs [avenanthramides], and phytosterols, and whether it exerted antioxidant and anti-inflammatory effects, as well as the capacity to improve relevant intestinal parameters, in an AOM [azoxymethane] / DSS [dextran sulfate sodium]-induced CRC [colorectal cancer] mouse model.

Suboptimal intake of whole grains (38 g/d) was associated with CRC burden across 16 European countries. An optimal intake of 50–100 g/d was considered in our study to establish the dose administered in the AOM/DSS-induced CRC mouse model (75 g/d).

Seeds (100 g) were soaked in distilled water for 12 h then watered daily. Temperature and relative humidity were set at 25 °C and 60%. Germination was performed in darkness for five days. Germination percentage was determined based on total number of fully emerged seedlings.

We reached 100% of germination and a radicle length of 6.47 ± 0.22 cm. Sprouts were dried at 50 °C for 12 h, milled to a particle size of 0.5 mm, and stored at 4 °C until analyses.

Protein and lipid contents were higher in SO, whereas carbohydrate and ash contents were lower. A more than four-fold increase [0.64 mg/g to 2.79 mg/g] in TPC [total phenolic compounds] was obtained after five days.

We identified AVA-D as the most abundant AVA, followed by AVA-L, which had not been reported as one of the three most abundant AVAs in other oat varieties. Of the three most abundant AVAs previously reported, only AVA-B had a higher abundance in germination.

Phytic acid, an antinutritional compound present in oats, was 10 times lower in oat sprouts. Phytic acid has its content decreased by 15%–35% during even a short three-day germination due to activation of phytase activity. Although high doses of phytic acid inhibit absorption of metals and minerals in humans, it has been observed that, in small doses, it can function as a protective factor in several chronic degenerative diseases.

Mice in groups 3 and 4 were gavaged every morning with phenolic-AVA extract (0.084 mg GAE) and 30 mg of SO, respectively. We observed a mild anti-inflammatory effect of SO and AVA treatments, and a reduced adenocarcinoma incidence of 52.5% and 21.3%, respectively.

SO was more efficient in activating the Keap1-Nrf2 signaling pathway compared to treatment with AVA. Oat phenolic compounds together with β-glucans may be acting synergistically, thus offering greater protection for cancer prevention and treatment.”

https://www.mdpi.com/2304-8158/9/2/169/htm “Chemopreventive Effect of the Germinated Oat and Its Phenolic-AVA Extract in Azoxymethane/Dextran Sulfate Sodium (AOM/DSS) Model of Colon Carcinogenesis in Mice”

The supplementary material developed this oat cultivar’s seed and sprout profiles for 138 phenolic compounds. It measured C-type AVAs, but not A-type AVAs.

This was my model study for Sprouting whole oats.

A second study was reviewed in Eat oats today! and repeated here:

“The first evaluation of anti-inflammation effects of A-type AVAs was published from our own group. Fifteen A-type AVAs from commercial sprouted oat products interacted with lipopolysaccharide-induced nitric oxide production and iNOS expression.”

https://pubs.acs.org/doi/full/10.1021/acs.jafc.9b06812 “Quantitative Analysis and Anti-inflammatory Activity Evaluation of the A-Type Avenanthramides in Commercial Sprouted Oat Products” (not freely available)

Oat variety and sprout age weren’t available for the six sprouted oat products tested, so oat seed-to-sprout comparisons weren’t possible. A-type AVA comparisons among products were performed, but weren’t meaningful due to unknown varieties, ages, product processing, and storage.

A third study compared four grains’ sprouted and unsprouted contents:

“Seeds were soaked at 25°C in 1 L of distilled water for 20 (brown rice), 12 (sorghum and millet) and 8 h (oat), respectively. Hydrated grains were allowed to germinate with layering over wet cellulose pads in a humid chamber for 60 h at 25°C (oat seeds) or 30°C (brown rice, sorghum, and millet seeds) with 95% relative humidity.

All seeds derived from brown rice and oat were germinated after 48 h in the humid chamber. Germinated grains were dried at 50°C until reaching a moisture content of 10%. Sample seeds were milled to fine flour, screened through a 100-mesh sieve and stored at 4°C for further analysis.

After 60 h of germination, sprout length in sorghum and millet ranged from 8 to 24 mm, while sprouts obtained from brown rice and oat ranged from 3 to 6 mm.

Compared to raw flours, germinated flours derived from brown rice, sorghum, and millet had lower gelatinization enthalpy, whereas germinated oat flour showed higher gelatinization enthalpy.

During germination, enzymes are activated, catalyzing starch degradation, which may disrupt the double helical structure of starch. Consequently, less energy is required to unravel and melt double helices of starch in germinated flours. The increase in gelatinization enthalpy of germinated oat flour may be due to dissolution of hydrolyzed starch granules during germination.”

https://link.springer.com/article/10.1007%2Fs10068-020-00770-2 “Influence of germination on physicochemical properties of flours from brown rice, oat, sorghum, and millet” (not freely available)

The first study sprouted oats for five days to full germination and a minimum radicle length of 6.25 cm. The third study sprouted oats to full germination in 60 hours and a 3 mm minimum total length.

At the same 25°C, with 60% relative humidity and daily watering, it took 120 hours to achieve full germination. With 95% relative humidity, it took half that time.

Was humidity a relevant difference in oat sprout growth? Would Choyang variety oat sprouts increase their minimum 3 mm total length more than 20 times between Hours 60 and 120 to match the minimum Turquesa radicle length?

This is a count of PubMed “oat sprout” search results, 20 results total:

A “broccoli sprout” search returned 648 results. Is oat sprout research just getting started?

Eat oats today!

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

This 2020 food chemistry review provided phenolic-compound reasons to eat oats:

“Phenolamides result from the conjugation of hydroxycinnamic acids with amines. These products contain a variety of metabolic, chemical, and functional capabilities due to the large number of possible combinations among the parent compounds.

Of the currently known phenolamides, the most common are avenanthramides (AVAs), which are unique in oats. AVAs possess anti-inflammatory, anti-itch, anti-atherosclerosis, antioxidant, anti-cancer, anti-obesity, anti-fungal, anti-microbial, and neuroprotective properties.

Twenty-nine C-type AVAs have been identified in oats, and twenty-six A-type AVAs.

  • C-type AVAs in commercially available oat products range from 36.49-61.77 mg/kg (fresh weight).
  • A-type AVAs represent approximately 22.5% of total AVA levels in regular oats and 24.7-33.0% in commercial sprouted oats.

Steeping raw groats increased AVA concentrations.”

These reviews were referenced:

“Since publication of these two reviews, a few new studies reported AVAs’ beneficial health effects, mainly related to their anti-inflammatory and anti-cancer activities. AVAs can:

  • Significantly decrease IL-6, IL-8, and MCP-1 in endothelial cells;
  • Inhibit IL-1β- and TNF-α-induced NF-κB activation; as well as
  • Expression of adhesion molecules; and
  • Adhesion of monocytes to endothelial cell monolayer.

In 2020, the first evaluation of anti-inflammation effects of A-type AVAs was published from our own group. Fifteen A-type AVAs from commercial sprouted oat products interacted with lipopolysaccharide-induced nitric oxide production and iNOS expression.

Colloidal oatmeal’s natural components, AVAs, help to restore and maintain skin barrier function. AVAs are safe, well tolerated, and can be effective as adjuvant treatment in atopic dermatitis.

In one mouse model, a C-type AVA was able to mitigate many adverse effects of Alzheimer’s Disease. It restored hippocampal long-term potentiation and synaptic function, enhanced memory function, suppressed pro-inflammatory cytokines TNF-α and IL-6 levels, reduced caspase-3 levels, and increased pS9GSK-3β and IL-10 levels.

AVAs downregulated expression of hTERT and MDR1, pro-survival genes for cancer cells, and COX-2 mRNA and PGE2 levels, known pro-inflammatory markers. AVAs induced apoptosis by activating caspases 8, 3, and 2.”

https://pubs.acs.org/doi/10.1021/acs.jafc.0c02605 “The Chemistry and Health Benefits of Dietary Phenolamides” (not freely available)

Hadn’t thought about sprouting oats before this paper.

Clearing out the 2020 queue of interesting papers

gettingwell4 2-3 stars Required further work, Acetylcholine, Brain development, Cerebrum, Cortisol, Dopamine, Epigenetics, Glutamate, Hippocampus, Hypothalamus, Immune system, Limbic system, Lower brain, Memory, Neurochemicals, Serotonin, Stress , , , , , , , , , , , ,

I’ve partially read these 39 studies and reviews, but haven’t taken time to curate them.

Early Life

  1. Intergenerational Transmission of Cortical Sulcal Patterns from Mothers to their Children (not freely available)
  2. Differences in DNA Methylation Reprogramming Underlie the Sexual Dimorphism of Behavioral Disorder Caused by Prenatal Stress in Rats
  3. Maternal Diabetes Induces Immune Dysfunction in Autistic Offspring Through Oxidative Stress in Hematopoietic Stem Cells
  4. Maternal prenatal depression and epigenetic age deceleration: testing potentially confounding effects of prenatal stress and SSRI use
  5. Maternal trauma and fear history predict BDNF methylation and gene expression in newborns
  6. Adverse childhood experiences, posttraumatic stress, and FKBP5 methylation patterns in postpartum women and their newborn infants (not freely available)
  7. Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double‐blind, controlled feeding study
  8. Preterm birth is associated with epigenetic programming of transgenerational hypertension in mice
  9. Epigenetic mechanisms activated by childhood adversity (not freely available)

Epigenetic clocks

  1. GrimAge outperforms other epigenetic clocks in the prediction of age-related clinical phenotypes and all-cause mortality (not freely available)
  2. Epigenetic age is a cell‐intrinsic property in transplanted human hematopoietic cells
  3. An epigenetic clock for human skeletal muscle
  4. Immune epigenetic age in pregnancy and 1 year after birth: Associations with weight change (not freely available)
  5. Vasomotor Symptoms and Accelerated Epigenetic Aging in the Women’s Health Initiative (WHI) (not freely available)
  6. Estimating breast tissue-specific DNA methylation age using next-generation sequencing data

Epigenetics

  1. The Intersection of Epigenetics and Metabolism in Trained Immunity (not freely available)
  2. Leptin regulates exon-specific transcription of the Bdnf gene via epigenetic modifications mediated by an AKT/p300 HAT cascade
  3. Transcriptional Regulation of Inflammasomes
  4. Adipose-derived mesenchymal stem cells protect against CMS-induced depression-like behaviors in mice via regulating the Nrf2/HO-1 and TLR4/NF-κB signaling pathways
  5. Serotonin Modulates AhR Activation by Interfering with CYP1A1-Mediated Clearance of AhR Ligands
  6. Repeated stress exposure in mid-adolescence attenuates behavioral, noradrenergic, and epigenetic effects of trauma-like stress in early adult male rats
  7. Double-edged sword: The evolutionary consequences of the epigenetic silencing of transposable elements
  8. Blueprint of human thymopoiesis reveals molecular mechanisms of stage-specific TCR enhancer activation
  9. Statin Treatment-Induced Development of Type 2 Diabetes: From Clinical Evidence to Mechanistic Insights
  10. Rewiring of glucose metabolism defines trained immunity induced by oxidized low-density lipoprotein
  11. Chronic Mild Stress Modified Epigenetic Mechanisms Leading to Accelerated Senescence and Impaired Cognitive Performance in Mice
  12. FKBP5-associated miRNA signature as a putative biomarker for PTSD in recently traumatized individuals
  13. Metabolic and epigenetic regulation of T-cell exhaustion (not freely available)

Aging

  1. Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches
  2. Epigenetic regulation of bone remodeling by natural compounds
  3. Microglial Corpse Clearance: Lessons From Macrophages
  4. Plasma proteomic biomarker signature of age predicts health and life span
  5. Ancestral stress programs sex-specific biological aging trajectories and non-communicable disease risk

Broccoli sprouts

  1. Dietary Indole-3-Carbinol Alleviated Spleen Enlargement, Enhanced IgG Response in C3H/HeN Mice Infected with Citrobacter rodentium
  2. Effects of caffeic acid on epigenetics in the brain of rats with chronic unpredictable mild stress
  3. Effects of sulforaphane in the central nervous system
  4. Thiol antioxidant thioredoxin reductase: A prospective biochemical crossroads between anticancer and antiparasitic treatments of the modern era (not freely available)
  5. Quantification of dicarbonyl compounds in commonly consumed foods and drinks; presentation of a food composition database for dicarbonyls (not freely available)
  6. Sulforaphane Reverses the Amyloid-β Oligomers Induced Depressive-Like Behavior (not freely available)

Eat broccoli sprouts for your eyes

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

This 2020 review subject concerned a leading cause of blindness:

“Advanced glycation end products (AGEs) are toxic compounds that have adverse effects on many tissues including the retina and lens. AGEs promote formation of reactive oxygen species (ROS), which, in turn, boost production of AGEs, a vicious cycle.

Diabetic retinopathy (DR) is a devastating microvascular complication of diabetes mellitus and the leading cause of blindness in working-age adults. The onset and development of DR is multifactorial. Lowering AGEs accumulation may represent a potential therapeutic approach.

Once AGEs are formed, most are irreversible. Cataracts are perhaps the earliest pathobiology of AGEs:

Nε-(carboxymethyl)-lysine (CML) [a representative AGE] in lens crystallins from diabetic (■) and non-diabetic (♦) subjects as a function of age.

The glyoxalase system is a protective mechanism that slows down synthesis of AGEs by limiting reactive dicarbonyls formed during sugar metabolism. Glutathione (GSH) in the eye is present at concentrations many times blood levels, and is a critical component of the glyoxalase system.

Proteomic analysis identified GLO1 [glyoxalase 1] as a protein differentially expressed in cells treated with sulforaphane. Sulforaphane inhibited AGEs-derived pericyte damage and delayed diabetes-induced retinal photoreceptor cell degeneration.

No AGE inhibitors have reached clinical use. The glyoxalase system and discovery of compounds that enhance this detoxifying activity represent a therapeutic alternative to fight glycation-derived damage.”

https://www.mdpi.com/2076-3921/9/11/1062/htm “Glyoxalase System as a Therapeutic Target against Diabetic Retinopathy”

The above graph – plotting a cataract AGE level against chronological age – represented life stage progression without effective personal agency, without taking responsibility for your one precious life.

Citation 156 was Activation of Nrf2 attenuates carbonyl stress induced by methylglyoxal in human neuroblastoma cells: Increase in GSH levels is a critical event for the detoxification mechanism (not freely available):

“The present study focused on the methylglyoxal (MG) detoxification mechanism. MG treatment resulted in accumulation of modified proteins bearing the structure of AGEs.

This accumulation was suppressed by activation of the Nrf2 pathway prior to MG exposure via pre-treatment with an Nrf2 activator:

Although pre-treatment with the Nrf2 activator did not affect mRNA levels of GLO1, expressions of GCL and xCT mRNA, involved in GSH synthesis, were induced prior to increase in GSH levels.

These results indicated that increase in GSH levels promoted formation of the GLO1 substrate, thereby accelerating MG metabolism via the glyoxalase system and suppressing its toxicity. Promotion of GSH synthesis via the Nrf2/Keap1 pathway is important in MG detoxification.”

Continued in Part 2.

PXL_20201121_113656177

Nrf2 and Parkinson’s disease

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This 2020 rodent study investigated a long non-coding RNA (lncRNA) in Parkinson’s disease:

“Knockdown of MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) lncRNA inhibited elevated nuclear factor (erythroid-derived 2)-like-2 factor (NRF2) expression, thereby inhibiting inflammasome activation and ROS (reactive oxygen species) production. MALAT1 was shown to promote neuroinflammation by recruiting enhancer of zeste homologue 2 (EZH2) to the promoter of NRF2, suppressing Nrf2 expression.

EZH2 catalyses generation of trimethylated H3K27 (H3K27me3) from histone H3 at lysine 27 (H3K27). EZH2 plays an important role in regulating the essential genes for inflammation in microglial activation, which induces neurodegeneration in the central nervous system.

Our results also validated MALAT1 binding to EZH2 in LPS-treated BV2 cells, which further recruited H3K27me3 to the gene promoter loci of Nrf2 to repress Nrf2 transcription. Although silencing MALAT1 did not alter global EZH2 expression levels, decreased binding between EZH2 and the Nrf2 promoter was observed. Previous studies have revealed that lncRNAs regulate the function of EZH2 in a similar manner.

MALAT1 epigenetically inhibits NRF2, thereby inducing inflammasome activation and ROS production in PD mouse and microglial cell models. To the best of our knowledge, it is first report of the important role of EZH2 in regulating the expression of Nrf2 to activate microglial inflammation.”

https://molecularbrain.biomedcentral.com/articles/10.1186/s13041-020-00656-8 “LncRNA MALAT1 facilitates inflammasome activation via epigenetic suppression of Nrf2 in Parkinson’s disease”

Eat broccoli sprouts today! referenced a letter to the editor that cited The Ezh2 Polycomb Group Protein Drives an Aggressive Phenotype in Melanoma Cancer Stem Cells and is a Target of Diet Derived Sulforaphane which found:

“SFN treatment is associated with reduced Ezh2 level and H3K27me3 formation.”

However, that study didn’t link sulforaphane’s main effect of Nrf2 signaling pathway activation to these specific treatment effects.

This post was inspired by our latest subscriber, Dr. Albert F. Wright, who is battling PD with – among other treatments – broccoli seeds.

Mild stress improves broccoli compound yields

gettingwell4 5+ stars Premium, Epigenetics, Memory, Stress ,

This 2020 plant study by the same university as Our model clinical trial for Changing to a youthful phenotype with broccoli sprouts investigated seasonal and stressful effects on broccoli compounds:

“In this study, three crop trials were carried out to evaluate effects of cultivation season, application of different dosages of methyl-jasmonate (MeJA) on overall quality and on total content of bioactive compounds of ‘Parthenon’ broccoli cultivated under field conditions of southeastern Spain.

Elicitation is the main tool used to increase content of secondary metabolites in vegetables, as it induces stress responses in plants. Several studies have involved application of elicitors to broccoli plants in order to improve their nutritional properties (although this application is more common for seeds and sprouts).

Content of total carotenoids, phenolic compounds and glucosinolates were higher in autumn compared with spring, showing increases of 2.8-fold, 2-fold and 1.2-fold, respectively. Moreover, a double application of MeJA increased contents of total carotenoids, phenolic compounds and glucosinolates by 22%, 32% and 39%, respectively, relative to untreated samples.

Controlled and timely (four days before harvest) application of 250 µM MeJA as an elicitor to aerial parts of plants, on two consecutive days, yielded florets of Parthenon broccoli with higher contents of bioactive compounds, without changing its overall quality.”

https://www.mdpi.com/2304-8158/9/10/1371/htm “Seasonal Variation of Health-Promoting Bioactives in Broccoli and Methyl-Jasmonate Pre-Harvest Treatments to Enhance Their Contents”

Findings by broccoli compound category were:

Glucosinolates

“Total content of GLSs was 2-fold higher in autumn than in spring. Total precipitation [2018] in spring was 361 mm compared with 185 mm in autumn. The water deficit in autumn could have contributed to the increase in total GLS content.

The main compound in samples of plants cultivated in spring (first and third assays) was glucoiberin (GIB), followed by glucoraphanin (GRA). The order was reversed in broccoli cultivated in autumn, with GRA being the main compound, followed by GIB, for all treatments.

Aliphatic GLSs were predominant in our Parthenon samples, representing on average 76%, 86% and 83%, of total GLSs in the first, second and third assays, respectively. In relation to the effect of MeJA on content of GLSs, neoglucobrassicin (NGB) was the only compound that showed a significant increase after application of MeJA in seasonal trials, since other GLSs decreased or did not differ with respect to the control group.

NGB increased significantly, from 0.3 mg/kg f.w., to 175 mg/kg f.w. in broccoli treated with two consecutive doses of 250 μM MeJA, and contents of GBSs, total indole GLSs and total GLSs also increased. In contrast, one single dose of 500 μM MeJA did not enhance contents of these compounds.”

Phenolics

“Contents of flavonols and chlorogenic acids were higher in autumn than in spring, whereas content of sinapic acid derivatives was higher in spring. Influence of light on individual phenolic compounds could explain the increase in flavonols and chlorogenic acid derivatives in autumn.

Although MeJA altered contents of phenolic compounds, this effect was not clearly associated solely with MeJA. We found a greater effect of the excipient and MeJA in autumn. When we added an extra stress factor – namely, MeJA – the impact was not as great as in autumn.”

Carotenoids

“In broccoli cultivated in spring, the order was β-carotene > lutein > violaxanthin > neoxanthin, while in autumn the order was β-carotene > violaxanthin > lutein > neoxanthin. Content of total carotenoids in broccoli cultivated in autumn (26 mg/kg) represented a 2.8-fold increase compared to broccoli grown in spring (9 mg/kg).

Treatment with MeJA significantly reduced total content of carotenoids in broccoli cultivated in autumn, whereas it did not show any effect on plants cultivated in spring, and in some cases even led to an increase in carotenoid content. Plants that received two applications of 250 µM MeJA content of carotenoids (34 mg/kg f.w.) increased in comparison with plants without this treatment (28 mg/kg f.w.) as well as those receiving one application of 500 µM MeJA (28 mg/kg f.w.).

Chlorophyll content was directly related to carotenoids content, with a strong correlation in autumn. Carotenoids absorb solar light in the spectral region not covered by chlorophylls and pass light energy to chlorophyll a, protecting it from harmful reactions that occur in conditions of excessive light, in the presence of oxygen. When high temperatures reduce content of carotenoids in spring, a reduction in total chlorophylls is also observed, possibly due to the photo-oxidation process.”