Designing an E4 Fasting trial...

[circular]

Anyone know how much Prolon costs? Might work well for my father.

AFA using it for an e4 trial, Prolon has soy and tomato, enough that in the FAQ they say it's not for people avoiding these. This might limit participation among e4s.

[Gilgamesh]

Circ, good point about the soy and tomato. I think Longo will eventually realize alt. versions of the diet should be offered.

George, your reasoning makes sense. I guess I'm actually less worried about the zero vs. a bit more calories problem than the matter of the pace of the caloric descent. Researchers observed that dropping adult rodents to 30% CR didn't lengthen their lives – it even shortened them a bit. So everyone assumed the CR only worked when instituted in childhood. Walford (and Weindruch, I think) then tried dropping the adult rodents down to the 30% CR level in three phases, separated by a month or so, as I recall. Voilà! They lived much longer lives.

Now, instituting rest-of-life CR in previous-life non-CR'd animals is very different from doing a periodic several-day fast or quasi-fast! But my concern is this: if a gentle descent makes a huge difference in the switching on or off of certain genes in one energy-restriction context, it might in another, as well – even if the different energy-restriction context is very different indeed. Going by feel and being keto-adapted may not be relevant here. Thousands of genes are expressed differently on CR. Those having to do with ketosis may only have to do with a tiny part of the beneficial effect.

I don't know. We're pioneers and have to take chances either way. (The question is what sort of chances to take.)

[Tincup]

Circ, good point about the soy and tomato. I think Longo will eventually realize alt. versions of the diet should be offered.

Though it defeats the convenience of packaged food, you can see exactly what Longo is doing in the patents and can duplicate it on your own. Also Gundry has a version of FMD in his Plant Paradox book. It seems to have a few more calories than Longo's. Also Longo, in the patent adjusts for body mass. If somebody cares, I can dig out the tables and post.

George, your reasoning makes sense. I guess I'm actually less worried about the zero vs. a bit more calories problem than the matter of the pace of the caloric descent. Researchers observed that dropping adult rodents to 30% CR didn't lengthen their lives – it even shortened them a bit. So everyone assumed the CR only worked when instituted in childhood. Walford (and Weindruch, I think) then tried dropping the adult rodents down to the 30% CR level in three phases, separated by a month or so, as I recall. Voilà! They lived much longer lives.

Now, instituting rest-of-life CR in previous-life non-CR'd animals is very different from doing a periodic several-day fast or quasi-fast! But my concern is this: if a gentle descent makes a huge difference in the switching on or off of certain genes in one energy-restriction context, it might in another, as well – even if the different energy-restriction context is very different indeed. Going by feel and being keto-adapted may not be relevant here. Thousands of genes are expressed differently on CR. Those having to do with ketosis may only have to do with a tiny part of the beneficial effect.

I don't know. We're pioneers and have to take chances either way. (The question is what sort of chances to take.)

Longo introduced fasting/refeeding cycles (or FMD) in mid-life in rodents. They had significant health span extension. He talks about it in his TEDx talk and interview with Rhonda Patrick -both linked in this post. This was very intriguing to me. In Jason Fung's fasting book, he notes that fasting acts very differently than CR. In one respect, metabolism is upregulated in fasting and downregulated in CR.

[Gilgamesh]

Interesting, George. Thanks. I really don't know that much about fasting, but given that I'll probably be doing it on a regular basis, I should hit the books! One thing about the early-onset failed CR attempts: many of these rodents were described as having "improved healthspan" (better biomarkers), but still didn't live longer, on avg. (but SOME did live much longer), even dying at a younger age than the controls, on average. Either way, I agree that the daily CR studies may only apply to a limited extent to fasting.

[circular]

Ben Greenfield recently interviewed Dr. Fung about fasting. I haven't had time to listen, and I'm not sure if there are any new angles for you guys there. I'm sure you're family with Dr. Fung already.

[Tincup]

Interesting, George. Thanks. I really don't know that much about fasting, but given that I'll probably be doing it on a regular basis, I should hit the books! One thing about the early-onset failed CR attempts: many of these rodents were described as having "improved healthspan" (better biomarkers), but still didn't live longer, on avg. (but SOME did live much longer), even dying at a younger age than the controls, on average. Either way, I agree that the daily CR studies may only apply to a limited extent to fasting.

Walford was Longo's mentor. In the cyclical studies, the mice had a significantly improved median lifespan, however the lifespan of longest lived mice were similar between the controls and the fasted/refed mice. The cyclical mice had significantly less cancer and other chronic illness & when they did get it, they got it much later. Personally, I'm much more interested in health span than life span.

Anyone know how much Prolon costs? Might work well for my father.

AFA using it for an e4 trial, Prolon has soy and tomato, enough that in the FAQ they say it's not for people avoiding these. This might limit participation among e4s.

I also just recalled that Gundry's version of Longo's FMD is available for order. (He mentions this in the book). One of his patients who went on his plan to fix her autoimmune issues is a chef and she created his 3-day "kickstarter" menus as described in the book. For the Gundry version of Longo's FMD, it is the vegan version of this kickstarter. On her website, you order the food with the vegan option and the blue KSP logo.

One friend tried it and thought it quiet tasty - I have no personal experience since I just fast - its a lot cheaper

[Tincup]

Interesting, George. Thanks. I really don't know that much about fasting, but given that I'll probably be doing it on a regular basis, I should hit the books! One thing about the early-onset failed CR attempts: many of these rodents were described as having "improved healthspan" (better biomarkers), but still didn't live longer, on avg. (but SOME did live much longer), even dying at a younger age than the controls, on average. Either way, I agree that the daily CR studies may only apply to a limited extent to fasting.

This is a Longo paper which addresses many parts of his FMD, including (appropriate here) motor coordination, memory, and neurogenesis. Also life & health span & etc.

[Gilgamesh]

George, thanks. I'm going to read all the FMD papers, and probably reread Mattson's work, now that one question I had has been solved: Is the experience of the FMD too unpleasant for me? Answer: not at all!

Starting June 8, here are my calorie totals for each day. 325 is today.

2220
1618
1061
755
468
400
374
325

Protein has gone from around 60 g/day to 18 g/day. That's veggie/nut protein, so the egg equivalent is much lower.

My previous attempts were much milder. Earlier, I wanted to test multi-day reduced energy-intake without doing the full-blown FMD.

But this, even going below Longo's human protocol, seems so easy I might even add another day tomorrow before ramping back up. Only problem is sleep, and only the last two nights, so far.

G

[apod]

George, thanks. I'm going to read all the FMD papers, and probably reread Mattson's work, now that one question I had has been solved: Is the experience of the FMD too unpleasant for me? Answer: not at all!

Starting June 8, here are my calorie totals for each day. 325 is today.

Wow, go G! Following a few rounds of FMD myself (maybe a year or so back?), I found my hunger seemed elevated for a solid week or two (maybe even a whole month toward the last round) bringing my cronometer up into the 3k/d range. I did around 3 rounds of it before I felt like I was losing muscle mass / energy. Post-FMD, you might try upping resistance training (+ carbs & protein?) for the refeed gains.

[Gilgamesh]

Hey apod. Yeah, I'm going to crank up the protein (and, a bit, carbs) for the next few days, and definitely emphasize resistance training (was doing that during the fast, actually).

I'm still plowing through Longo's work. Uncertain about how to do the "immune-rebuilding" part of the diet. I'm not sure he knows, since the work is still so knew. But 4–5 days of higher protein intake seems like a good idea.

G