Month: October 2023

Plasmalogens, Part 1

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The person who knows the most about this subject is Dayan Goodenowe, PhD. Some recent publications include:

https://www.frontiersin.org/articles/10.3389/fcell.2022.864842/full “Targeted Plasmalogen Supplementation: Effects on Blood Plasmalogens, Oxidative Stress Biomarkers, Cognition, and Mobility in Cognitively Impaired Persons”

https://www.frontiersin.org/articles/10.3389/fcell.2022.866156/full “Brain ethanolamine phospholipids, neuropathology and cognition: A comparative post-mortem analysis of structurally specific plasmalogen and phosphatidyl species”

plasmalogens and cognition

A sample of links freely available at https://drgoodenowe.com/.

1. Presentations to professional groups. Have your mouse ready to click the pause button.

https://drgoodenowe.com/dr-goodenowe-presents-at-the-iagg2023-in-yokohama-japan/ “A rare children’s disease that may be the key to reversing neurological decline in aging”

Includes videos of a treatment’s effects on a child.

https://neomarkgroup.wistia.com/medias/0qln0wy93t “The most influential biomarkers for aging and disease”

Despite the title, a considerable number of studies were presented on prenatal, infant, and early childhood development. He misspoke a few times, so read the slides.

“Phenotype is reality. Genotype is possibility. Communications links between different fields are very poorly connected in science.

Peroxisomes are islands. They don’t have DNA like your mitochondria do. Peroxisomal transport issues are important things to understand.

All aging-related cross-sectional analyses are on the rate of decline. You’re declining from a previous well state. Age-matched controls are the most ridiculous thing to do.”

2. I’ll highlight the longest of several interviews because there was plenty of room to expand on points. Maybe the best detailed explanations came as responses to that interviewer challenging with contrasting AD, traumatic brain injury, and cholesterol paradigms. Its transcript is more accurate than a usual YouTube interpretation, but there are still mistakes such as “fossil lipid” vs. phospholipid.

https://www.betterhealthguy.com/episode186 “Plasmalogens with Dr. Dayan Goodenowe, PhD”

“Science is how do you push things to its failure, until you can’t fail it again. We’ve lost that. It’s become more hypothesis proving.

Plasmalogens levels go up for a different reason than people think. The reason why it peaks in our 40s and 50s is because we’ve been myelinating. The white matter of our brain is still increasing. It’s not because we’re making more plasmalogens. It’s because the lake, the reservoir, gets full. What you’re measuring in blood is overflow from the lake. The lower plasmalogens start trickling down in your blood, the bigger drain that’s occurring on that system.

Low plasmalogens don’t just predict dementia in the elderly population. It predicts the rate of decline of that dementia. It predicts the rate of death.

The biggest drivers of plasmalogen manufacturing and the biggest reasons why they decrease with age, or in other circumstances is two things. One, the failure to maintain a fasting state of the human body. The second one is muscle atrophy.

Amyloid has absolutely nothing to do with Alzheimer’s, or dementia. It’s just a bystander on the road watching an accident happen.

Age-related cognitive decline is clearly where plasmalogens have the greatest impact. You’re always going to have mixed pathologies in the brain.

Nutritional availability of plasmalogens is virtually non-existent. As soon as they hit the hydrochloric acid of your stomach, they’re gone. They don’t make it past the stomach, or the upper intestine.”

I came across Dr. Goodenowe’s work last month from clicking a comment on this blog that linked back to her blog. Always be curious.

Continued in Part 2.

Dietary choline

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Two 2023 papers on choline intake, beginning with an analysis of 14323 people:

“Choline is an essential ingredient that is required for many biological processes in the human body, including formation of cell membranes, preservation of liver and kidney function, and production of neurotransmitters. For humans, only a small amount of choline can be endogenously generated through the liver. It is vital to supplement it in the diet to prevent deficiency.

Mean dietary choline intake was 316.5 ± 164.1 mg/d, and incidence of cardiovascular disease (CVD) was 8.8% in study participants.

nutrients-15-04036-g002

New findings of our study are as follow:

  1. In contrast to previous studies, higher dietary choline intake was associated with a lower incidence of CVD, especially incidence of stroke, in this large, nationally representative US population.
  2. The protective role of higher dietary choline intake was accompanied by reduced inflammation and heart rate.
  3. In the subgroup study, higher dietary choline intake – in participants aged ≥60 years, and in participants with BMIs < 30 kg/m2 – was found to be a protective factor for the presence of CVD.

Our results suggest that adequate choline intake acts against CVD, and choline deficiency should be avoided.”

https://www.mdpi.com/2072-6643/15/18/4036 “Association between Dietary Choline Intake and Cardiovascular Diseases: National Health and Nutrition Examination Survey 2011–2016”

A randomized control trial investigated choline intake effects on resistance exercise training:

“Choline plays crucial roles in several physiological processes, such as:

  • Neurotransmission, muscle contraction, and force generation via synthesis of chemical messenger acetylcholine;
  • Lipid transport via lipoprotein synthesis; and
  • Methyl-group metabolism as a precursor to betaine.

It supports cell membrane integrity/function as a precursor to phosphatidylcholine. Choline may also affect muscle responses to exercise via betaine, which is important for gene expression/protein synthesis.

The present study determined effects of different amounts of choline intakes (approximately 50%, 70%, and 120% of Adequate Intake (AI)) on muscle responses to resistance exercise training (RET). Three groups of 50-to-69-year-old healthy adults underwent a 12-week RET program, and submitted >48 diet logs (>4x/week for 12 weeks). Participants were randomly assigned to one of three choline groups in a double-blind manner: zero additional egg yolk (low), one additional egg yolk (medium = med), or three additional egg yolks (high) per day. 

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  • We found that low choline intake (~51% of AI) resulted in diminished strength gains compared to choline intakes of ~68% or ~118% of AI.
  • We observed that a high choline intake (greater than AI) did not provide additional positive effects on RET responses.
  • Together with choline, betaine was independently associated with change (%) in composite strength, suggesting that multiple mechanisms are at work.
  • There was no effect of choline consumption on any blood lipids and lipoproteins, indicating that a moderately low choline intake may not negatively affect blood lipid profiles.
  • Dietary cholesterol did not contribute much to variability of strength gains.

The consistency of about 50% of AI is particularly significant, as much as 40% of the older population is consuming this low level of choline where there are no overt clinical signs of deficiency, and considering potential effects of choline on age-associated loss of muscle function. This research was supported by U.S. Poultry and Egg Association.”

https://www.mdpi.com/2072-6643/15/18/3874 “The Effect of Choline and Resistance Training on Strength and Lean Mass in Older Adults”

For over a decade, I supplemented phosphatidylcholine via a small amount of lecithin every day. I stopped that three years ago when I started supplementing betaine, thinking that I wouldn’t need as much choline oxidized to plentiful betaine.

Don’t have any choline blood tests to indicate whether or not that has been the right decision. It seems like there’s more risk than reward in continuing, though, so I’ll restart 1200 mg lecithin next week at $.07 a day. That provides about the same amount of choline as does one egg.

Rocket launch followed by telemetry plane

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Activate Nrf2 to improve arthritis

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This 2023 rodent study cited Eat broccoli sprouts for arthritis to test a Nrf2 activator’s effects on rheumatoid arthritis:

“We show that activation of Nrf2 efficiently improves arthritis of SKG mice, which develop T cell-mediated autoimmune arthritis by zymosan A injection. Oral administration of CDDO-Im, a representative chemical inducer of Nrf2, had effects of both prevention and treatment toward arthritis of SKG mice in an Nrf2-dependent manner.

1-s2.0-S0891584923005452-gr9_lrg

We also found that Nrf2 activation through myeloid-cell lineage-specific Keap1 disruption did not achieve significant improvement in arthritis of SKG mice. Systemic Nrf2 activation or Nrf2 activation in other lineage cells including T cells, B cells and fibroblast-like synoviocytes linage cells is important for improvement of rheumatoid arthritis.

We propose that Nrf2 activation is an efficient therapeutic approach for rheumatoid arthritis.”

https://www.sciencedirect.com/science/article/pii/S0891584923005452 “Nrf2 activation improves experimental rheumatoid arthritis”

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A flawed broccoli microgreen study

gettingwell4 0-1 star Wasted resources

Sometimes I wonder why knowledgeable researchers design studies they know are wastes of time and resources, yet they perform them anyway. I’ll stop at three items this 2023 human study did that these researchers knew weren’t right.

1. Subjects’ bioavailable sulforaphane amounts from a single 16-gram serving of broccoli microgreens weren’t going to be anywhere near the lab-created sulforaphane amount. Human bioavailability doesn’t work like that, and a broccoli microgreens serving needed to be at least doubled in order to be within achievable range of other studies.

There wasn’t any reason in the Discussion section to waste the reader’s time with guesses about finding “Total mean urine SFN metabolite excretion over the 2-day study was 50.5 ± 2.7 μmol..total excreted SFN metabolites was less than the 100 µmols consumed.” They knew.

total urine sfn metabolites

2. If these researchers wanted to improve subjects’ broccoli microgreen bioavailability, consume a serving by itself, not with bagels and orange juice. Okay, a small amount of broccoli microgreens first thing in the morning probably doesn’t taste all that pleasant. But subjects couldn’t do this one time?

I’ve eaten cruciferous 3-day-old sprouts (after microwaving them to create sulforaphane and other isothiocyanates) by themselves to start my day every day for three and a half years now, eating nothing else before, then waiting an hour after. Like my healthspan depends on it.

3. They cited three studies that found eating broccoli for a minimum of fourteen consecutive days changed gut microbiota composition. It’s silliness to analyze why a single serving didn’t have similar effects. If this study’s design was of suitable length, they could have produced the same finding from Day 1 measurements.

So what’s this dumbing down of sulforaphane research all about?

  • Is it that researchers just aren’t serious about advancing their field?
  • Do they have to burn through funding regardless of flawed designs to keep people employed?
  • Some kind of academic equity requires the least knowledgeable person to be in charge?
  • Or do problems with wastes of research resources lie elsewhere?

https://www.mdpi.com/2304-8158/12/20/3784 “Sulforaphane Bioavailability in Healthy Subjects Fed a Single Serving of Fresh Broccoli Microgreens”

If professionals in medical-related fields cared about people, they would..

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Last month I came across an immune system inflammation biomarker I hadn’t known about, suPAR (soluble urokinase plasminogen activator receptor). This subject went into a queue of things I also didn’t know about, and I got around to looking at its 2023 research earlier this week.

It turns out suPAR was discovered in 1991. How some suPAR evidence fits into a segment of existing medicine and research will bore you to tears if you read https://www.mdpi.com/1422-0067/24/15/12376 “Plasminogen System in the Pathophysiology of Sepsis: Upcoming Biomarkers” up through Section 4.4. But it does thoroughly explain what suPAR is.

ijms-24-12376-g001

This paper managed to avoid addressing the point of 2018’s The arrogance of a paradigm exceeding its evidence as well as epigenetic findings of 2023’s Sex hormones and epigenetic clocks. I couldn’t find a better 2023 suPAR starting point, though.

Other 2023 suPAR papers bickered and equivocated using speech constrained by researchers wanting to keep their jobs and add to their CV. How about publishing papers telling the truth about whether or not quality medical care was provided using suPAR inflammation information? Since inflammation’s progression with disease or age isn’t exactly a mystery, what are suPAR’s prospects?

The most heartening 2023 paper I read provided good guidance for young adults:

“For verification of predicted correlations between plasma levels of suPAR and cardiovascular risk factors in younger populations, the current study analyzed data from young and healthy adults aged 25–41 years. A statistically significant inverse correlation between suPAR plasma levels and the HDL serum levels was found in male and female populations, as well as higher suPAR plasma levels in smokers compared to nonsmokers and past smokers.

A major strength of our study is the young and healthy study population lacked any relevant comorbidities, thus minimizing possible interference by unknown confounders. Investigating correlations of biomarker suPAR with cardiovascular risk factors and overall cardiovascular risk in a young and healthy population is important, since preventive measures to reduce the burden of cardiovascular risk factors and diseases should take place before irreversible damage is set.”

https://www.mdpi.com/2075-4418/13/18/2938 “The Association of suPAR with Cardiovascular Risk Factors in Young and Healthy Adults”

Higher suPAR in this study indicated preclinical symptoms with low-grade inflammation. If young adults ignore this signal, and don’t individually take responsibility for their own one precious life by investigating inflammation’s source, they may not be able to reverse later clinical conditions of many inflammation-related diseases.

The most disheartening paper provided details about how suPAR biomarkers continue to be ignored:

“We find that as a prognostic biomarker suPAR is challenged in it becoming as an object for clinical practice in the emergency department by the power of diagnostic practices and the desire for experience-based scripts that quickly enable the clinician to reach the right diagnosis. Although suPAR is enacted as a promising triage strategy suggesting a low or high risk of disease, the inability to rule out specific diagnoses and producing the notion of secure clinical actions make its non-specificity and prognostic character problematic in clinical practices.”

https://link.springer.com/article/10.1057/s41292-022-00296-2 “Challenges facing the clinical adoption of a new prognostic biomarker: a case study”

Didn’t agree with philosophical abstractions throughout this paper regarding a “new” biomarker from 1991.

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Canadian Thanksgiving

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Canadians were in dire straights yesterday, needing something to not be depressed about. It isn’t that US citizens are less depressed, but we have our Bill of Rights 1st and 2nd amendments that we adhere to.

Several of the people on this three and a half hour conversation were Canadians. Will you listen to them?

I learned a lot, such as possible transgenerational inheritance of effects from worldwide coerced actions. Bhakdi shortly after the 1 hour 6 min point was the easiest to understand, and also the scariest.

So what were you thankful for yesterday? Exposing facts?

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But their taste

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Two 2023 human studies of cruciferous vegetables’ consumer acceptance, starting with five species’ 7-day-old sprouts and 17-day-old microgreens:

“Sensory chemistry of Brassicaceae species is complex, reaching gustatory, olfactory, and pain nerves and receptors. Among organosulfur compounds, glucosinolates, their hydrolysis compounds, and sulfur-volatile compounds are responsible for their taste, aroma, and trigeminal characteristics (mainly, bitter taste, sulfurous aroma, and pungency/spicy sensations, respectively).

This work compared the sensory profiles and consumer acceptance between (S)prouts vs (M)icrogreens of the same species (kale, radish, rocket, broccoli, and mustard) under the same growing conditions, correlating them with phytochemical composition. On each sampling day (3, 5, 7, 12, 15, and 17 days), S&M were harvested, frozen, and freeze-dried for further analysis.

Previous studies reported the decrease of glucosinolates and sulforaphane from day 4 of germination. Previous studies also indicated that designing crop improvement strategies for sensory traits based on ∑GLS content would be flawed, as it does not consider relative differences in sensory characteristics of different GLSs and isothiocyanates, nor contributions from other GLS hydrolysis products.

table 3

Consumers tested 5 brassica species’ 7-day-old sprouts and 17-day-old microgreens. Each consumer was served ∼ 10 g of each sample coded with 3-digit numbers and the questionnaire. Water and unsalted crackers were provided between samples for palate cleaning.

Consumers were asked to taste each sample, express their overall liking and ‘attribute’ liking using a 9-point hedonic scale (1 = dislike extremely, 5 = neither like nor dislike, and 9 = like extremely). The question ‘How much do you like the ‘attribute’ of this sample?’ was used for global satisfaction/overall, and different attributes (appearance, leaves color, hypocotyl color, size, bitterness, spicy, astringency, herbal-vegetal and ID flavor).

  • Differences among samples depended more on brassica species than growing stage (S&M).
  • In rocket S&M, no attributes were found in the critical corner. RocketS and RocketM were also characterized by the lowest values of ∑GLS. RocketS presented the highest GLS5 glucoerucin content, which does not have bitter taste.
  • Although no differences were found in global, bitterness, and spicy consumer satisfaction degree between S&M of radish and mustard species, penalty analysis indicated a need to improve excess intensity of bitterness and spicy in RadishS and MustardS.

4 out of 5 sprout samples needed improvements, while only 2 out of 5 microgreens samples needed improvements. Sprouts are richer in organosulfur compounds than microgreens, although it depends on the species.

An interesting research line would be to study odor-active compounds of these products and link them with consumer preferences. Other vegetable crops could be included, such as cereals and legumes.”

https://www.sciencedirect.com/science/article/pii/S0925521423001722 “How does the phytochemical composition of sprouts and microgreens from Brassica vegetables affect the sensory profile and consumer acceptability?”

This study treated all conditions to 16 hours light/8 hours darkness throughout. If I wanted naturally developed sprouts at Day 7, I’d follow other studies’ methods and keep germinating seeds in darkness through Day 3 to simulate their natural below-ground conditions, then provide white or blue light after Day 3. So I consider this study’s 7-day-old and 17-day-old sprouts to be both microgreens because they got their leaves at Day 3.

Hadn’t thought of a pain aspect to eating sprouts before reading this study. I’d guess a consumer’s hedonic rating of “dislike extremely” would correspond.

I switched to equal starting weights of broccoli, red cabbage, and mustard seeds 2+ years ago during Week 56 to produce 3-day-old sprouts. That combination takes the edge off individually unpleasant attributes while preserving their beneficial effects.

Couldn’t do that with radish sprouts earlier this year. I might try again if my right thumb doesn’t stop hurting, after I find a tactic that tones down their intensity.

An association analysis of 2129 adults aged 40–80 years found:

“The proportion of participants who ate cruciferous vegetables over two days was 29.5% among bitter tasters, significantly lower than that (35.7%) among non-tasters (P = 0.04) after adjustment of age, gender, race/ethnicity, dietary energy intake, physical activity, education, smoking, and income levels.

cruciferous veg intake and obesity

Bitter taste sensitivity was associated with less consumption of cruciferous vegetables and a high likelihood of obesity, which may mediate its association with diabetes.”

https://pubs.rsc.org/en/content/articlelanding/2023/FO/D3FO02175K “Bitter taste sensitivity, cruciferous vegetable intake, obesity, and diabetes in American adults: a cross-sectional study of NHANES 2013–2014” (not freely available)

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Bridging Nrf2 and autophagy

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Three more 2023 papers that cited Precondition your defenses with broccoli sprouts, starting with a review:

“Examining crosstalk between Nrf2 antioxidant signaling and autophagy provides insights into how they are interconnected and proteins that mediate their communication. These factors are potential therapeutic targets for diseases with both autophagy dysfunction and oxidative stress.

A working model illustrates mechanisms of bridging factors (SQSTM1, TFEB, Sestrin2, TRIM16, Ca2+, and miRNAs) connecting autophagy (left) and the main antioxidant Nrf2-Keap1-ARE pathway (right) and feedback loops between these factors.

fcell-11-1232241-g003

  • A network forms that connects Nrf2, SQSTM1, TFEB, and mTOR.
  • Other non-canonical autophagy regulatory proteins like Sestrin2 and tripartite motif-containing protein 16 (TRIM16) also participate in regulation of Nrf2 and mTOR via direct or indirect interactions.
  • Ca2+ is the most widespread intracellular messenger whose role in autophagy has been studied extensively.
  • At post-transcriptional level, microRNAs have been reported to impact both the regulation of autophagy and Nrf2 antioxidant signaling.

Since these regulatory proteins seem intricately entangled, potential side effects in practical scenarios should also be taken into consideration. Further studies on understanding the complex crosstalk between autophagy and antioxidant pathways are yet to be conducted.”

https://www.frontiersin.org/articles/10.3389/fcell.2023.1232241/full “An update on the bridging factors connecting autophagy and Nrf2 antioxidant pathway”

A second review subject was improving autophagy:

“Lysosomes are crucial degradative organelles that maintain cellular homeostasis. During the pathogenesis of neurodegenerative diseases and aging, functions of lysosomes are impaired, and lysosomal degradative capacity is consequently reduced.

Transcription factor EB-mediated lysosome biogenesis enhances autolysosome-dependent degradation, which subsequently alleviates neurodegenerative diseases. Small-molecule compounds that enhance TFEB activity and lysosome biogenesis are potential therapeutic agents.”

https://journals.lww.com/nrronline/fulltext/2023/11000/enhancement_of_lysosome_biogenesis_as_a_potential.7.aspx “Enhancement of lysosome biogenesis as a potential therapeutic approach for neurodegenerative diseases”

A third review tied mitochondrial participation into these processes:

“Mitochondria play an essential role in neural function, such as supporting normal energy metabolism, regulating reactive oxygen species, buffering physiological calcium loads, and maintaining the balance of morphology, subcellular distribution, and overall health through mitochondrial dynamics. Given recent technological advances in the assessment of mitochondrial structure and functions, mitochondrial dysfunction has been regarded as the early and key pathophysiological mechanism of cognitive disorders.

Mitochondrial dysfunction caused by acute and chronic brain injury is difficult to be distinguished because they may exhibit similar structural and functional impairments. Mitochondrial physiological function and morphology are integral, so when one is damaged, the other is also involved.

We recommend that all of the above methods can be used to explore mitochondrial dysfunction in different pathological pathways of cognitive disorders. Results may be related to special pathological pathways, sensitivity of the method, experiment cost, and degree of proficiency.”

https://journals.lww.com/nrronline/fulltext/2024/04000/latest_assessment_methods_for_mitochondrial.18.aspx “Latest assessment methods for mitochondrial homeostasis in cognitive diseases”

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Three years after

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A delayed commemoration of Week 9 of Changing to a youthful phenotype with broccoli sprouts:

Yes, Awakening continues to be a common occurrence due to continuous broccoli compound intake. Understanding what I didn’t understand yesterday. Noticing what I couldn’t see yesterday. I’m sure there’s more to go.

Appreciate last week’s experiences with people associated with my fourth grandchild’s birth. So miraculous, so beautiful that everything happened when it needed to. She’s perfect.

The current idiocracy prohibits saying anymore.

Ripe wild persimmons. They really taste good if you wait until they’re completely ripened.

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