Designing an E4 Fasting trial...

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Sandy57
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Re: Designing an E4 Fasting trial...

Post by Sandy57 »

Thank you Susan.

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Re: Designing an E4 Fasting trial...

Post by Tincup »

Sandy57 wrote: Just a quick question, are you guys retired? The reason I ask is that I already have a decent size post saved as a draft addressing this issue. My commitments with work, and helping Sandy, training etc. would make it impossible to do multiple day fasts.
Hi Sandy,

Happy Birthday!! I'm about two years older. As to being retired, I am not. I do have a flexible work schedule, having been self employed for 30ish years. Before my demented mother passed 4 years ago, I had sole responsibility for organizing her care, though not in my home, so I'm aware of those demands. As to fasting, working & other commitments. Fasting doesn't impact my other activities. I've been keto adapted since Oct 2009. I've fasted 22 hours/day for two years and did two-12's for years before that. All my workouts and other activities are fasted. I've done a hard day of skiing (34,000' vert, off piste', double black EX terrain at 12,500') starting at 40 hours fasted without negative impact. In fact my quads, which normally tire because of my less than stellar form felt better than usual for that volume. I asked two researchers about this. One said it might be that ketones help clear lactate faster, another chalked it up to serum pH. On the other hand, I did have a negative impact on a similar day on day five of a fast. Not that I couldn't do it, but was not as energetic as usual. I don't always measure serum values, but on day five glucose is typically in the 50's (mg/dL) and ketones in the 6's (mmol/L). A TRX bodyweight workout is not impacted by the fasting. I've also done Tabatas with very minimal degradation in work output during the exercise. As to my normal office work, it is not impacted at all. Even though my ketone levels are high during fasting, I can't tell the difference between 0 mmol/L and 6.7 mmol/L on my mental function.
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Brian4
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Re: Designing an E4 Fasting trial...

Post by Brian4 »

We had spoken some time ago about encouraging Longo to do a fasting trial in humans, and, as I recall, his response was that he was more interested in doing mice studies.

Looks like he's launching a trial with his diet and dementia. No info on whether he's stratifying for APOE status:

https://www.beingpatient.com/fasting-mimicking-diet/

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Re: Designing an E4 Fasting trial...

Post by Fiver »

I wonder if the planning of a trial could work backwards. Instead of seeking funding, then seeking subjects maybe we could all show up, ready to enroll. Can you imagine? All of us just waiting in the lobby of some university or the NIH? :D
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Re: Designing an E4 Fasting trial...

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Fiver, great idea! Eager subjects, ready to follow protocols exactly, possessing lots of medical records – not easy for researchers to find.
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Re: Designing an E4 Fasting trial...

Post by Fiver »

Sounds like a problem that could be solved by a dating app. Matching subjects to trials. ;)
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Re: Designing an E4 Fasting trial...

Post by NewRon »

https://www.beingpatient.com/fasting-mimicking-diet/

"Gallstone formation goes way up for people who fast regularly for 16 or more hours, and they may need their gallbladder removed. If people skip breakfast, they also face an increased risk of cardiovascular mortality, so I would not fast for 16 hours unless you have to. I would stick with 12 hours."

Hmm....not exactly comforting, nor compatible with Gundry's advice.
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Re: Designing an E4 Fasting trial...

Post by BrianR »

NewRon wrote:https://www.beingpatient.com/fasting-mimicking-diet/

"Gallstone formation goes way up for people who fast regularly for 16 or more hours, and they may need their gallbladder removed. If people skip breakfast, they also face an increased risk of cardiovascular mortality, so I would not fast for 16 hours unless you have to. I would stick with 12 hours."

Hmm....not exactly comforting, nor compatible with Gundry's advice.
I certainly don't have St. Valter Longo's expertise, but I wonder about those assertions. My guess is that they're based on questionable epidemiological studies, rather than well designed controlled trials. (I'd certainly like to see citations.)

Regarding skipping breakfast, see, e.g., The Skeptical Cardiologist:
BREAKFAST IS NOT THE MOST IMPORTANT MEAL OF THE DAY: FEEL FREE TO SKIP IT (2013)
FEEL FREE TO SKIP BREAKFAST AGAIN (2015)
IGNORE THE NEW YORK TIMES AND THE AMERICAN HEART ASSOCIATION AND FEEL FREE TO SKIP BREAKFAST (2017)

From Eric Topal's tweet on the most recent (last week?) skipping breakfast study: "No cause and effect, if it (association) is real, a marker for what?, nutritional "science," Ugh." He also cited this somewhat balanced discussion https://www.inverse.com/article/55187-s ... fast-costs which actually seems to side with the breakfast skipping is horrible propononents, but notes:
On the other hand, skipping breakfast may just be a stand-in for other harmful lifestyle choices that can impact heart health. Speaking to CNN, Krista Varady, Ph.D., an associate professor of kinesiology and nutrition at the University of Illinois at Chicago who wasn’t involved in the new study, implied that Bao’s team’s research also presents evidence to that effect.

“However, the major issue is that the subjects who regularly skipped breakfast also had the most unhealthy lifestyle habits,” Varady said. “Specifically, these people were former smokers, heavy drinkers, physically inactive, and also had poor diet quality and low family income.”

In the paper, the authors acknowledge that skipping breakfast might just be a “behavioral marker” of other risky factors, as Varady suggests, but they argue that their statistical adjustments helped offset those factors. Ibáñez also notes the power of their evidence but adds that health factors are so multidimensional that it is impossible to adjust for everything.
(Personally, I generally like eating breakfast, although I eat it later in the morning now. But I wouldn't worry about skipping it, at least if I was keto adapted.)
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Re: Designing an E4 Fasting trial...

Post by aphorist »

Gallstone formation is a common occurrence in starvation and extended fasting. Whether or not it appears over the course over repeated 16-18 hr fasts, probably depends on a lot of factors.

1. In terms of meal timing, I think circadian rhythm biology (chronobiology) trumps all. If NAD+ slowly rises during the middle of the day on a NAMPT mediated basis, why shouldn't we be eating mid-day?

2. If the body has a hormonal cortisol awakening response, which in part upregulates a glucose respones from the liver, then why would one eat first thing in the morning to dump additional glucose ontop of the body's own hormonal milieu?

I think eating mid-day and maybe a late afternoon snack/small meal no later than 5 PM is ideal.
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Re: Designing an E4 Fasting trial...

Post by mike »

I've done 3 extended day fasts (2+ weeks) without any gallstone issues, while my wife, who had her gall bladder removed has had trouble with extended fasts. For IF, she is using digestive enzymes.
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