Received: by 10.194.29.164 with HTTP; Tue, 26 Mar 2013 06:45:59 -0700 (PDT)
Received: by 10.194.29.164 with HTTP; Tue, 26 Mar 2013 06:45:59 -0700 (PDT)
Date: Tue, 26 Mar 2013 09:45:59 -0400
Message-ID: <CAGT9wm2f-gETokCVrjKQs92OSmOwN_BpsDVnNHuGw5jqjcvn9g@mail.gmail.com>
Subject: Discussions w/ Luigi Fontana
From: Dean Pomerleau
To: The CR Society Main Discussion List <cr@lists.calorierestriction.org>

All,

I had good chat w/ Luigi Fontana upon my arrival at WUSTL for additional tests as part of his on-going studies of long term CRONies (12 of us as of now).

Luigi is doing well. Very busy. Lots of publications pending, including one on our muscle biopsy data that he says looks amazing - all 15 CR participants look remarkably similar to each other, and remarkably different from controls. He briefly went over what biomarkers he was measuring, and from what I can recall I believe they were things like markers of inflammation, cytokines, interlukins and stuff like that :-). I hope to learn more of the details tomorrow. He basically wants to do the same sort of analysis with the colon biopsy he's doing on us during this latest round of testing (sigmoidoscope procedure tomorrow - fun, fun, fun), since cells in the colon wall turn over more frequently, and are more susceptible to cancer, a current focus of his work (in addition to delving more into the important parameters of protein restriction).

He's been talking to both primate CR groups, (NIA & Wisconsin) and seemed to lend credence to some of the explanations for between group differences, and the overall relatively modest (if any) improvement relative to controls in the CR animals - e.g. the diet of the NIA monkeys was better, and the NIA control group was mildly CRed relative to the truly ad lib Wisconsin controls. He said they haven't published papers on more of the biomarker data from either group of CR primates (e.g. IGF-1, Cortisol, sex hormones) because they didn't show consistent results - further suggesting something weird was going on with the primates, since rodents and we long-term human CRONies show similar responses across our two species, and within the CRONie group, as his 2007 paper showed.

Speaking of consistent biomarkers of CR, and regarding my own situation, he wasn't particularly helpful. When I asked questions about "how low is too low?" (with regard to IGF-1, BMI, or any biomarkers of successful CR) he repeatedly said that we just don't know, even for rodents, to say nothing of people. He said recent data in another lab suggests different strains of mice respond differently to CR - some live longest on 40% CR (and don't live as long with more severe CR) while others live longest all the way up to 70% CR. He said if he had the money, he'd do studies to determine what biomarkers are indicative of an animal being in the CR "sweet spot", but alas he lamented that NIH funding goes more to yeast and biochemical pathway research than seemingly more informative animal and human experiments. Funding he says is tough for his kind of research, but he's getting by on some government grants and some private funding.

But if he had to guess, he said I'm taking a risk being as low as I am in some of the markers (particularly IGF-1), and thought it would be wise to gain some weight. He said it would be safer, and referred, for example, to difficulty I might experience recovering from an ccident (e.g. car crash) that might make it hard for me to volitionally gain or maintain weight necessary to heal (e.g. if in coma or otherwise impaired state).

When I asked what he would add to my diet, either in terms of macronutrients or specific foods, he was very non-committal. When I asked what HE eats, to probe what he consider to be the best diet for humans, he was also pretty vague - apparently because he varies his diet a lot, and partly because he said we just don't know - really good studies haven't been done, and the best diet for a person may depend on their genes (I may be putting words in his mouth on that last part though...).

Luigi's diet sounds pretty much classical Mediterranean as conceived of when people refer to such a diet. Lots of veggies, quite a bit of olive oil (from olives  he growns himself at his home in Italy and takes to the press himself! He doesn't know with any precision how much EVOO uses - he just drizzles it on), just a little in the way of nuts (in a morning smoothie he makes with a variety of mostly fruit ingredients), whole grain bread he bakes himself, lots of pasta, some meat (~once per week) and fish (~ once per week), and maybe an ounce or two of very good quality Italian cheese per week.  He didn't know even the approximate macronutrients of his diet, but it sounds like low protein, relatively high in complex carbs, moderate fat, mostly from olive oil. He likes to vary his diet a lot - says its healthy to challenge the body with a variety of foods over time - so that it doesn't get used to the same thing over-and-over. I asked if there were studies to support the benefit of this way of eating, and he said he didn't know of any, but his intuition tells him its so.

When I last visited a few years ago, he was an avid cyclist, getting quite a bit of exercise through biking. I asked about it, and he admitted he hasn't been cycling too much lately, a little bit so he won't be totally out of shape when he goes mountain biking for fun in Italy when he returns in the summer. He has recently started some weight training (about 1 hour per week) again. I'm guessing his relatively sedentary lifestyle its partly a function of how busy he is with career and family (says he's in the midst of writing 10 papers at the moment!). But he said its partly its because its not clear to him how much benefit exercise for the sake of health (as opposed to exercise like mountain biking, for pleasure) will buy someone who is eating a healthy diet and not overweight. My impression is that he clearly believes diet trumps exercise in determining ones health and longevity. He said the importance of a good QUALITY diet as important (as opposed to the old mantra "its only the calorie intake that matters") seems to have been supported by the longer life of the NIA primates (with a more whole food diet) relative to the Wisconsin primates.

While he remains quite thin, he said he doesn't consider himself to be practicing CR, and doesn't personally see the tradeoff as worthwhile - he wouldn't want the reduction in quality-of-life he said he's expect from practicing serious CR. I said part of my (and others) motivation for practicing CR is to contribute to the science of human nutrition, health and longevity, for which he is the torch bearer (when it comes to human CR). He said he was planning to continue with his investigations, despite the funding challenges, which was encouraging.

That's about all I can remember for now from our discussions. I ran these notes by Luigi before posting them, and while he said some of the details aren't entirely correct, they are close enough to post them.

I'm doing the test procedures today and then traveling home, so I likely won't be able to respond to any questions or discussion until tomorrow.

--Dean