I wish! Your conference looks really good. If I weren't sitting on a panel for this one, I'd be tempted to attend they're slightly too far apart for me to justify both. We're going to have to rely on you to pose my question to Dr. Longo. Dr. Frank Longo is presenting at mine. My bad .
Oh, drats! One of these days we'll overlap. Would love to come up to go to your conference, as well, but I have to head to Asia again immediately after the USC conference.
Brian, here's what I dumped onto Facebook (which some here may have seen):
A few quick summary points from Longo's conference.
<> *General*
It’s clear that restricted eating improves health in humans, and probably slows aging at least a bit.
It’s not clear what the best sort of restriction is.
(LOTS of studies ongoing, so we’ll know more in the coming year or two.)
Benefits accrue regardless of macronutrient choices.
But reducing protein, or specific amino acids, may by itself improve health.
On the other hand, at least one study (by Michelle Harvie) looked carefully at daily CR vs. a 5:2 diet (isocaloric) using a normal protein diet (50 g protein/day in obese women), and saw equal improvement in metabolic health (and weight loss) in both groups.
<> *Key questions and guesses at answers*
- Macro nutrient choices?
A couple studies show reduced energy-intake is beneficial even with a normal amount of protein, but I think moderate protein is likely best. In rodents, adding certain amino acids to CR’d rodents (usually those found in high quantities in meat) to achieve normal or slightly high levels can reduce the benefits of the restriction.
As for low-carb vs. low-fat, we don’t know. I’m eating low-carb now because I feel a bit better on it in some ways, and my biomarkers look very good after eating this way for a couple years (but they looked good before). Longo’s FMD, and Luigi Fontana’s recently tested diet are not low-carb, and both diets improved health and markers of rate of aging.
- Daily narrow eating window, 5:2, or Longo’s FMD, or something else?
We don’t know, but, personally, I plan to mix them up in my own practice, in order to enhance “metabolic flexibility” (often used to refer to the ability to switch between lots of carbohydrates and lots of fat, but I mean it in its other sense).
Several studies show eating in a narrow window, compared to grazing (or a large window), even if isocaloric, is better for health.
I asked the people who did a time-restricted eating study, with the eating window early in the day, whether they planned to do a study with a later restricted eating window (since many people don’t want to skip dinner). Answer: yes.
Insulin-sensitivity normally peaks in late morning. This might be a reason to have an early time-restricted feeding window.
See my upcoming blog post on “when the heck autophagy really starts in humans after they stop eating”. Link will be posted on Facebook (first, I have to start a blog...).
<> *What if you didn’t want to do any calorie/food restriction but wanted to get the benefits of CR*
- Eat a plant-based diet (will likely have less protein).
- Eat a lot of garlic, since H2S probably mediates some of the effect of CR.
- Increase NAD+ levels (infusions, patches, or nicotinamide riboside – other options will be available soon).
- Take resveratrol (at least 100 mg, not near to when you exercise) to increase Sirt1 expression.
- Consider rapamycin. I’ll be doing a very high-dose trial for 5 or so weeks soon and will report on that. The 5 mg/week protocol, which many are trying, probably is way, way too low.
- Consider metformin. I’d love to see evidence that it works in healthy humans, but, absent that, it might still be a good bet. Can only guess at right dose, but 500 mg twice a day if you're in good shape, a bit more otherwise, is what many are trying.
<> *Miscellaneous*
One day of fasting for a rodent may be the equivalent of several days for a human. So translation of rodent work in this area is tricky.
People, even really old people (90) get better at handling long fasts with each cycle of fasting. (This, from work at Charité in Berlin).
Brian4 wrote:Brian, here's what I dumped onto Facebook (which some here may have seen):
Fantastic, thanks!!
Brian4 wrote:On the other hand, at least one study (by Michelle Harvie) looked carefully at daily CR vs. a 5:2 diet (isocaloric) using a normal protein diet (50 g protein/day in obese women), ...
Brian4 wrote:
<> *Miscellaneous*
One day of fasting for a rodent may be the equivalent of several days for a human. So translation of rodent work in this area is tricky.
Dr. Kroemer: So what we did on circulating leukocytes is that we needed to wait for three or four days to see a massive induction of autophagy. There's a fundamental difference between rodents and humans, and so, the two days that you have been alluding to cause a 20% weight loss in mice, that are, at this time point, at the verge of death. Another day would potentially kill them. And so, 20% is a lot, so imagine this for yourself.
Rhonda: In two days.
Dr. Kroemer: In four days, a human being only loses one to two percent of his or her weight.
Rhonda: Is that because they have a higher metabolism, rodents do, or...?
Dr. Kroemer: Yeah, it's certainly linked to the change in the surface volume ratio that is classically associated with an accelerated metabolism.
I have an acquaintance who was on day 35 of a fast a few days ago. He was thin to begin with and his "goal" is a 15% weight drop. He may be about there but wasn't at day 30.
He does this once a year, plus an time restricted feeding schedule where he only eats before solar noon. He front loads his protein in this schedule. Has his 88 year old mum (he's an Aussie) on the same program (she only fasts for 15 days). She was hit by a 15 ton truck 15 years ago and sustained very serious head injuries. She was effectively written off by her docs. She is doing very well now.
Tincup, thanks – very useful info. I've been reading the work of Guido Kroemer and I'm now convinced autophagy, at least in most tissues, takes at least three days to kick in in humans. It might take longer in the brain.
But the Fontana paper Kroemer cites of members of the CR Society was intriguing: continuous CR, with zero fasting, also turns on a constant, low-level autophagy.
Brian, 50 g is high enough that it doesn't count as "protein restriction", but you're right that it's probably a bit lower than average for the UK.
Brian4 wrote:
<> *Miscellaneous*
One day of fasting for a rodent may be the equivalent of several days for a human. So translation of rodent work in this area is tricky.
Dr. Kroemer: In four days, a human being only loses one to two percent of his or her weight.
Rhonda: Is that because they have a higher metabolism, rodents do, or...?
Dr. Kroemer: Yeah, it's certainly linked to the change in the surface volume ratio that is classically associated with an accelerated metabolism.
I also have done some longer fasts. It does get easier with each one. I've done a 13, a 17, and a 19 day water only fast, in that order. On the last one I got to 10% weight loss. How fast you lose will vary based on many factors, not least of which is how over weight you are to begin with. Your body is smart - it will try harder to hold onto weight if you have little fat. It also knows enough not to break down heart muscle, when there are other less critical material available. Also, while muscle is certainly lost while fasting, much of this is not whole cells, but rather shrinkage of cells that quickly regain themselves after the fast ends and adequate nutrition is available. I'm two weeks into re-feeding, and my fasting blood glucose started by rising 10 points a day going from 85 during the fast up to 207, but then started going down 9-10 points a day to 159 this morning. This was predicted based on mouse and human cell culture tests - beta cells are reduced during fasting, but come back after. Prior to the fast, my fasting sugars were in the 220-230 range. I'm not 100% back physically, but I'm close. After each fast, expect to put at least half of what you lost back on. Stem cells at work. That is the hope, anyway.
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