Eat broccoli sprouts for your bladder?

February 29, 2024February 29, 2024 gettingwell4 2-3 stars Required further work Control group

A 2024 clinical trial investigated effects of people adding a cup of cruciferous vegetables to their daily diet for six months:

“We developed a 6-month behavioral dietary intervention (Power to Redefine Your Health [POW-R Health]) designed to increase Cruciferae intake and isothiocyanate (ITC) levels in non–muscle-invasive bladder cancer (NMIBC) survivors, with the long-term goal of reducing bladder cancer recurrence, progression, and mortality.

Orally ingested ITCs are rapidly and almost exclusively delivered to the bladder and concentrated in the urine, showing 2 to 3 orders of magnitude higher concentration of ITCs and metabolites in the urine than in the plasma within 3 hours of dosing. Storage of urine in the bladder further enhances exposure of malignant cells to ITCs.

We estimated dietary ITC intake and measured urinary ITC levels. With the exception of urinary ITC levels in µM, the treatment arm had a significantly higher increase in levels in all variables compared with the control arm from baseline to 6-month follow-up.

Our POW-R Health intervention increased Cruciferae intake by 0.94 cups/day and urinary ITC levels by 11.1 μmol/g creatinine compared with the control arm, with an average increase of urinary concentration of 10.4 μM, the desirable dose level of urinary ITCs needed to stop or kill at least 50% of bladder cancer cells in in vitro models. To our knowledge, this is the only study that showed an intervention’s success in significantly and meaningfully increasing both Cruciferae intake and urinary ITC levels among NMIBC survivors.

Our simple dietary intervention only requires NMIBC survivors to consume 1 cup of Cruciferae a day, is of low cost to participants (cost of Cruciferae), and is easily accessible (available at grocery stores). If a future RCT demonstrates that the intervention significantly reduces bladder cancer recurrence and progression, it would be an easily scalable strategy to prevent NMIBC recurrence and progression, which occurs within 5 years in most NMIBC survivors.”

https://jnccn.org/view/journals/jnccn/aop/article-10.6004-jnccn.2023.7086/article-10.6004-jnccn.2023.7086.xml “Outcomes of a Dietary Intervention to Reduce Bladder Cancer Recurrence and Progression in Survivors of Non–Muscle-Invasive Bladder Cancer”

These researchers took a result of “an average increase of urinary concentration of 10.4 μM” and touted it as evidence of the intervention’s success. The first paragraph of clinical trial NCT04548193’s primary objective was:

“Develop an evidence-based behavioral intervention to increase cruciferous vegetable intake, with the goal of attaining desirable urinary isothiocyanates (ITC) levels effective for anti-cancer activities.”

No mention in this study’s Discussion section of why 10.4 ± 22.5 µM was so wildly variable. After all, nobody’s measurements of excreted ITCs (aka bioavailability) were below zero as the standard deviation implies (10.4 – 22.5 µM ?).

How much did “estimated dietary ITC intake” contribute to variability in this trial’s measurement goal? Reference 26 “Total isothiocyanate yield from raw cruciferous vegetables commonly consumed in the United States” shared a few coauthors with this study, and had items such as:

“We observed up to 345-fold difference in isothiocyanate yield among nine samples of mustard green (ranging from 0.4 to 137.9 μmol/100g wet weight).”

Reference 25 “Effects of cooking methods on total isothiocyanate yield from cruciferous vegetables” also shared a few coauthors with this study, and had items such as:

“The efficiency and amount of ITCs generated by gastrointestinal microflora could be relatively low and vary substantially by individuals.”

But differences in cooking methods and raw cruciferous vegetables weren’t the only explanations for this primary outcome’s wild variability. These researchers knew or should have known about the 2016 https://onlinelibrary.wiley.com/doi/abs/10.1002/mnfr.201600766 “Stabilized Sulforaphane for Clinical Use: Phytochemical Delivery Efficiency” (not freely available).

Per that study of 10 healthy people’s metabolisms after ingesting a 200 μmol isothiocyanate sulforaphane amount (35 mg), urinary % of dose amount excreted ranged from 19.5% to 86.9%. Statistics wouldn’t add any plausible explanations of why there were >four times individual differences in ITC bioavailability.

So we’ll have to wait for follow-on studies.

Kingfisher

Sulforaphane’s effects on autism and liver disease

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

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

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

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

Studies were conducted in male rats and boys only;

The sample size of our clinical study is relatively small [6 SFN-treated boys] and needs to be further expanded in the future; and

This study only uncovered a potential link between gut flora and the therapeutic effects of SFN on ASD.

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

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

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

“Dosing was weight-based:

Two tablets/day for 10–29 lb;

Three tablets/day for 30–49 lb;

Four tablets/day for 50–69 lb.

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

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

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

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

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

Antioxidative defense (catalase, superoxide dismutases, thioredoxin reductase);

Iron metabolism (ferritin heavy chain (FTH1), ferroportin 1);

Glutathione (GSH) synthesis (cystine-glutamate antiporter system, cystathionase, glutamate-cysteine ligase catalitic subunit, glutamate-cysteine ligase modifier subunit, glutathione synthetase); and

GSH recycling – glutathione reductase (GR)

were reversed/increased by sulforaphane treatment.

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

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

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

Herding humans

February 6, 2024February 7, 2024 gettingwell4 4-5 stars Advanced knowledge, Beliefs, Memory Control group, Reciprocity

Three recent papers cited a 2009 Herding in humans paper, starting with a 2024 modeling study by one of its coauthors showing that people have trouble purposefully acting randomly:

“In many tasks, human behavior is far noisier than is optimal. Yet when asked to behave randomly, people are typically too predictable.

Randomness is produced by inhibition of habitual behavior, striving for unpredictability. We verify these predictions in two experiments: people show the same deviations from randomness when randomly generating from non-uniform or recently-learned distributions.

While local sampling has previously explained why people are unpredictable in standard cognitive tasks, here it also explains why human random sequences are not unpredictable enough.”

https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1011739 “Explaining the flaws in human random generation as local sampling with momentum”

A 2023 study tested extents to which people could be influenced to change their food preferences:

“We examined the effect of a descriptive norm on the choice between two similar products (vegetables or fruits). Participants were exposed to a norm promoting vegetables, fruits, or no norm.

A descriptive norm signaling that a greater proportion of previous participants had chosen a vegetable over a generally preferred fruit basket tripled the odds of participants choosing vegetables. These findings support the concept that descriptive norms act as heuristics that influence behavior in a relatively automatic manner.

The norm may have acted as a social proof heuristic to which participants conformed with little deliberation. Given that they were asked to add their name to a list of previous participants’ names and choices, they may have inferred that their choice would be visible to participants after them.

We found no to small effects of norms on intentions to consume fruits and vegetables or on taste expectations and experiences in a taste test, suggesting that these may not be key in explaining how descriptive norms lead to behavior change. Although the fruit norm did not affect choice, it did reduce negative fruit taste experiences compared to the no norm group.”

https://www.tandfonline.com/doi/full/10.1080/15534510.2023.2261178 “I’ll have what they’re having: a descriptive social norm increases choice for vegetables in students”

I selected this 2023 modeling study from many other modeling studies because it provided details about what researchers consider herding’s underlying premises to be:

“Herding does not come about because a central actor tells the agents to herd, but rather it is an emergent phenomenon of many local decisions, wherein the beliefs and thoughts of individuals become aligned. Herding is a form of social contagion, where one individual adopts the views of another, primarily because it increases their confidence in a decision they were making.

Herding is related to conformity, an important behavior in humans’ social learning, being a tendency to act as the majority of the individuals do. Conformity is defined as choosing the most frequent strategy observed by the player, instead of being guided by maximizing their personal payoffs.

The cost of herding occurs when someone decides to make the opposite decision of the rest of the herd. It is important to realize that these costs are only incurred if the actor has adopted a herd mentality. If they do not care about the herd, they do not suffer social costs.

In cases where everyone is herding, cooperation will prevail. Having a herding mentality has a positive overall effect, and can explain why cooperation prevails even without altruism, kin selection, tags, and reciprocity.”

https://www.cell.com/iscience/fulltext/S2589-0042(23)02004-7 “The evolution and social cost of herding mentality promote cooperation”

I’d guess that these coauthors never told their children that wrong is wrong even when everyone else is doing it.

It made me laugh that both the 2009 paper and this paper defined herding as solely happening on its own without any herders’ involvement. I have no doubts that researchers are not allowed to investigate and/or publish factual evidence on more advanced techniques of herding humans, especially those that have been widely used during this decade.

Our grandchildren’s grandchildren

February 3, 2024February 3, 2024 gettingwell4 Just me

Starting this blog’s tenth year with admitting to a National Geographic Alaska show compulsion. There’s something fascinating about seeing a subsistence lifestyle that I’d never choose.

1. A recent Life Below Zero: First Alaskans episode “Rite of Spring” included a visit to remains of a childhood home that had been swept away in a 2009 Yukon River flood. Some of the dialog:

“He put in his will that this land wasn’t ever to be sold or divided. It was for his grandchildren’s grandchildren.”

Nice thought. It’d be better, though, if a person would be around to see that generation of their descendants. Which is impossible when someone risks their survival day after day.

2. A Life Below Zero: Next Generation episode “Uneven Ground” showed a couple and their child repairing an access road, to include clearing trash from their property that’s on a former military installation. I’d guess that there’s a zero percent probability that they weren’t also exposed to leftover environmental toxins in their property’s soil and water.

3. Speaking of which, the park I played in as often as possible until age twelve was mentioned in two articles published decades afterwards:

“They’ll have to deal with toxic waste from incinerator ash dumped on the land as fill that’s buried up to four feet deep. Redevelopment of a water park at the adjacent Grapeland Heights Park required removal of 80,000 tons of soil at a cost of $10 million. Soil tests conducted by DERM in 2006 showed elevated levels of several contaminants, including barium, copper, and dioxins.”

The Melreese Toxic Gamble

“Toxic trouble at the Melreese site was also well-known. The city got an expensive lesson in the problem in 2005, when buried ash with dangerous levels of arsenic, lead, and other contaminants were found at Grapeland Heights Park, the popular park with ball fields adjacent to Melreese.”

Toxic soil under golf course is a legacy of Miami’s dirty past. There’s a lot more out there

I haven’t had toxicity tests after learning about this a few years ago. Too easy to get thoughts, feelings, and behavior trapped in What was not, is not, and will never be.

4. My oldest grandchild and I had a conversation about their environmental angst, which apparently was due to just reading about pollution. I didn’t say much, or sugarcoat anything, or otherwise dismiss concerns.

I think my teenaged grandchildren will be alright, but it’s also up to each of them and their own actions. Too early to expect to see their grandchildren.

I get pollution and death reminders on every beach walk from brown foam and washed up debris of formerly living things. Focusing on those aspects would take away from a beach walk’s other experiences.