Nov 21, 2018
How to live forever the Fasting Episode
Jody: Guys, I don’t want to die.
Matt: Shut your mouth
Jody: Sorry. I’m just scared.
Mike: Seriously, keep your pie hole shut
Jody: What did I say?
Matt: You’re not hearing us. Just don’t eat, man. You can talk. Just quit shoving calories down your gullet.
Jody: And I’ll live forever?
1:00 - 2:40
Mike: Ok, so no you’re not going to live forever, but if you want to extend your life, then honestly, simply eating less is probably the absolute best way to do it. And that’s a pretty cheap, easy intervention.
Matt: Except it’s not completely simple. Yes, calorie restriction has to been shown to really lead to increased longevity in a lot of animal models. It not only leads to longer life, but better longer life as well and extends median and maximal life span in rats, mice, fish, flies, worms, monkeys, and yeast.
Jody: That’s really exciting. I can’t wait to tell my pet yeast and flies. They’re gonna be so pumped. What about humans? That’s what I happen to be. Or pretty close to it.
Mike: Great point. Yes, it’s pretty difficult to replicate some of these studies in human. You can double a fly’s life span in a study and it only takes about 2 weeks to get results and no one is crying over not being able to go out for pizza with their friends. So, it’s both hard to extrapolate this data, and it’s hard to repeat in humans.
Matt: Right, but we we do know a few things…...we think. The fact that we see this effect in multiple species means it “probably” applies to many other species not studied, including us because it doesn’t seem to be a species specific adaptation, and when it applies to primates, it usually applies to us. And there was that really great U of Wisc study of primates where they restricted calories by 30%, and the monkeys were living to be the equivalent of like 130 in human years. And, they were living better! Less calories reduces metabolic rate and oxidative damage and improve age-related markers like insulin resistance. So, you don’t just live longer. You actually age more slowly, which is different. It’s better.
2:40 - 3:50
Jody: Sold. I’ll just cut 30% off my cheesburger and fries and live forever with the amazing, disease free body I have now.
Mike: Well…….if it was that simple we wouldn’t be talking about it.
Matt: You’re gonna rain on our parade and talk about the brain integrity study, aren’t you.
Mike: Yep. It’s almost like you and I have discussed this before. Jody, before you or your grey mouse lemur primate go balls to the wall with calorie restriction you should check out the study at Nature.com just this year. Yes, these lemurs lived longer. 50% longer. So, translating that to humans that’s like going from 80 to 120, and they seemed to live better like the other studies with reduced aging-associated diseases and preserved brain white matter. BUT, they had accelerated loss of grey matter in the cerebrum.
Matt: Ok, ok. So, yes, Jody probably doesn’t have much grey matter to spare. But what does this mean exactly? They still had all those benefits, just like all the other studies as well, and this one, single downside. Seems like the balance of benefit to harm is still pretty heavily in the benefit category, right?
3:50 - 4:50
Mike: Well, probably. And like you and I have discussed in the past, we may be able to moderate or eliminate that downside by getting a little more clever than a simple, strict 30% calories restriction forever.
Jody: The suspense is killing me. Any chance we skip the talk of IGF, gene transcription, protein synthesis modulators, etc and just tell me what to do.
Matt: We got you. We’ll give you some action points, but let’s geek out just a bit more for the science nerds out there. Let’s dig into this lemur study. I love this study because these primates are very similar to humans, not just metabolically, but also when it comes to their brain aging. They get amyloid lesions, which correlates to Alzheimer’s in humans, so we think they’re a very good model to compare to. So, let’s discuss. Jody, why would you care about your grey matter and if it atrophies?
Jody: Seems bad. What do you mean?
Matt: Well, you’re brain isn’t going to look worse in a bikini with atrophied grey matter. Your thick skull has it hidden. So, why do you care?
4:50 - 5:40
Jody: Well, I don’t want to pee my pants and forget my kid’s name when I’m old.
Matt: Exactly. It’s obviously the effect that’s important. And luckily for us, they studied that’s it. The headline of the story is that the grey matter atrophied, and that’s what everyone was talking about. But when you look at these monkeys’ performance on motor and cognitive tests they actually didn’t really have a drop off. So, I would absolutely hate for anyone to throw the baby out with the bathwater based on this and say not to calorie restrict because of this MRI finding that no one showed actually had a clinical effect.
Jody: So…...it doesn’t matter if the grey matter atrophies. Or it does matter.
Matt: That’s an easy answer. I have no idea. I’m just saying, we have real clinical benefits, and there are what LOOK like negative effects on MRI, but absolutely no proof of clinical negative effects.
Jody: So, you’re not worried about grey matter atrophy?
5:40 - 6:50
Matt: I definitely didn't’ say that. I want my grey matter to be plump and robust as possible if I had a choice, but I don’t want to give this more credit than it’s due. You’ll notice that CR actually had sparing effects on the white matter. So, I have no idea what this means. Performance wasn’t affected one way or the other in this small primate study. There’s clearly a big benefit to calorie restriction, and if we somehow can mitigate this quote-unquote problem, then I’m all for it. If I figure out how, then I’m all in. Otherwise, I’m still a big fan of CR. Let’s just talk about how exactly now.
Jody. Yes, lets. Because the more I think about it, I’m not sure I actually want to cut 30% off my cheeseburger the rest of my life.
Mike: Well, I don’t think you necessarily have to. You see the reason CR works is because, we think it reduces things like the igf-1 axis and the tyrosine kinase pathway. Both of these functions are active in the fed state and can lead to aging, cancer, diabetes, heart diseases. But CR and fasting also works by activating cellular mechanisms for autophagy and apoptosis. Autophagy means to eat one-self.
Jody: Dude, that doesn’t sound good.
6:50 - 8:40
Mike: I know, but what if your cells are just eating the weak broken-down parts of themselves. That's an oversimplification of the process, but basically calorie restriction induces a fasting state that leads to your cells looking to themselves for nutrients and energy. They automatically activate autophagosomes which scavenge the cell for broken proteins, old organelles, mitochondria, and other structures in disrepair. In essence, it’s a way for your cells to be out with the old and in with the new. Without fasting, or calorie restriction, you’re cells don’t go into autophagy and don’t get the chance to clean out themselves. Apoptosis, is similar, although it happens on a higher level, leading to cellular destruction of old broken cells and eventually replacement with new ones. Both, mechanisms occur in response to CR or fasting and are the panacea of longevity research right now. The idea being that cell rejuvenation and regeneration leads to management of and prevention of chronic diseases such as diabetes, CVD, Alzheimer's, autoimmune diseases, basically anything that can kill you.
So, getting to my point, you don’t have to activate these pathways with strict chronic calorie restriction for the rest of your life, turns out you can turn these pathways on and off relatively quickly, and still gain some of the benefits without losing 30% of your calories.
For example, anybody that follows this literature knows about the man, the myth, the legend. Valter Longo. He’s shown pretty good results with his fasting mimicking diet, which is not as difficult as traditional fasts, probably has the same benefits, and I have personally used………..
8:40 - 12:35
Matt: Ok, so I have some issues with the FMD. My first issue is that they sell a product to go along with it. Now, when I first heard this I completely dismissed the whole thing outright. Honestly, it made me a little mad. I had always felt like the CR data was not only very convincing because of its sophistication, but also because I’m very, very skeptical of medical research as a whole because there’s just so much stinking money from pharmaceutical companies and so many conflicts of interest that it’s hard to trust. But what could be more free from conflict than something that is the absence of consumerism or paying for pills. Who benefits from you buying and eating less? So, it just really ticked me off to see a product all of the sudden tied to the research. Of course, I then found out later that Dr. Longo donates his shares to a non-profit and doesn’t take money from it. So, I have massive respect for Dr. Longo and his work and I’m not suggesting anything nefarious of the man, but I’m still a little skeptical of this product. I don’t think it should be hard for people to get the same benefits, just as easy, without buying something. Having said that, I totally get that having a pre-packaged meal may mean higher compliance and benefit for more people. I get it. There’s just something about eating food from a wrapper that will always bother me, especially if I can get the same results without doing that.
So, for me, what I recommend to my family and do myself is a similar 5 day FAST with homemade bone broth instead of their packed product. Obviously, you have to be careful about your protein intake in general if you want to true benefits of fasting and the autophagy, but someone with my metabolism can take a pretty good amount of bone broth and get those results. We’re not going to go into the signaling and issues around too much protein right now. I really don’t think we’re approaching those levels of protein with what I propose. And I feel comfortable having my mom, who doesn’t have my metabolism take 12-16 oz of bone broth per day during her fasting period. And, honestly, there are so many great benefits of such a nutritionally dense food as bone broth that I prefer that to their packaged product even if both were free. I think it’s a better choice personally. All that collagen, minerals, etc. Yes, I understand that making bone broth is more difficult than buying the products. But if you could see the look on my dog’s face when she gets the leftover bones, that’s priceless man. Of course, you could totally do a 5 day water fast if you’re super hard core. But one of the things I liked about Longo’s most recent study is that he had a 75% compliance rate. I do not think that would have been possible with a strict fast. And no reason to torture people if we really could get similar results without the pain.
12:35 - 14:00
Jody: Ok, so 5 days per month of FMD, either with their product as a support like bone broth. I would love to have your glowing skin and youthful joints, Matt, by getting that extra collagen protein in my diet. What about intermittent fasting? Useful? Do that also? Instead of this?
Matt: Well, define intermittent fasting. What do you mean?
Jody: I mean, skipping breakfast basically. Eat dinner at 8p and don’t eat again until noon the next day. So, 16 hour fast each day.
Matt: Right, so that’s what most people mean with IF. I think a better term is just time-restricted feeding. And I’m a huge fan. I do that exact protocol, and I try to restrict my feeding window to as small as possible. 8 hours, from noon to 8 is good, but if I can get it down to 6 hours from 2-8 or even 4 hours and eat only between 2-6pm, or even just eat one big meal in the evening then I think there are great benefits to that. Studies have shown that to be an independently positive thing to do for body composition and other markers even if you eat the exact same amount of calories. So, yes, doing this is great regardless of whatever else you do with more prolonged fasts.
14:00 - 15:15
Mike: I think it’s important to recognize the differences though between time restricted feeding and prolonged fasting or a fasting mimicking diet. To truly activate autophagy you need to be in a fasting state, and for the most part, we think you need to diminish your glycogen stores. Now that might be possible if you throw in a hardcore workout into a short fast, but for the most part, we think it takes 2 days or more to activate autophagy. I have not seen or heard of autophagy occuring at any meaningful level with just 24 hours of fasting. And not with time restricted eating. Not to say those are bad for you, just they don’t activate autophagy.
Personally, I do both. Time restricted eating, and less regularly, I’ll go a FMD or a prolonged fast. That way you get the metabolic and hormonal advantages of time restricted eating, along with the apoptosis, autophagy, and longevity advantages of prolonged fasting.
15:15 - 19:30
Matt: Plus when you refeed after a prolonged fast you get stem cell activation that re-grows healthy cells leading to organ and tissue rejuvenation. So, that’s why I don’t straight 30% calorie restrict every day like in these studies. That’s a great study protocol to apply to rats or monkeys for years at a time. But that’s tough. It sucks to eat 30% less of the cheeseburger the rest of your life. I think it’s much easier to time restrict my calories, but still totally feast at the end of a long day, and then only occasionally muster up the willpower to do a prolonged 3-5 day fast. Most days, I’m active. 4 kids, multiple jobs. I need the calories. But time restricting both gives me health benefits and more freedom with my time honestly. Having to only worry about 33% to 66% as many meals as other people means I can spend that time and energy on reading esoteric studies on time restricted feeding.
(Discussion about when to eat during the day between Mike and Matt. What time is the best time to eat based on the science and what works for your family and life situation)
19:30 - 21:25
Jody: Sweet, I’m sold. So, tell me EXACTLY what to do?
Matt: Well, I think we’re close to agreement, but here’s where it gets tricky. Mike and I agree on a lot of things but animal fat is not one of them.
Mike: Yeah, I’ve got the genetics that prevent me from managing dietary saturated fat appropriately, so I go with Longo’s vegetarian version of the FMD, plant based products and protocol. When I’ve done the FMD, I’ve done 800 cal/day for 5 days. I usually skip breakfast, just have black coffee. Then have a small lunch and dinner. Usually soup and a salad. Lots of veggies, maybe some pasta in the soup, or lentils. Sometimes some hummus and carrots. But the overall goal is the same. I go for 50% calories from fat, 40% from carbs and 10% or less from protein. The low protein is key so you don’t activate the IGF-1 axis or tyrosine kinase pathway. You need a relative amino acid
21:25 - 23:00
Matt: And I’m not against that. I just think we can do better. Look, I eat the vast majority of my calories from plants and am a huge believer in the healing powers of plants and all the phytochemicals and benefits of a plant based diet. But I also believe we’re totally evolved to derive big benefits from the right type of animal nutrients. Grass fed, humanely raised, homemade bone broth is my jam. I say follow the guts of the protocol with respect to total calories, but I’m gonna give you my bone broth I make. My bone broth has about 100 calories per 10 oz. 5g fat and 7g protein. And I want you to eat super nutrient dense foods the rest of the time that have amazing benefits for detoxification (broccoli), brain health (sardines and walnuts), and sanity (coffee)
23:00 - 25:35
Here it is
Day 1: 1100 calories
32 oz (2 jars) - 320 calories - (lots of pink himalayan sea salt, pepper, and some turmeric)
16 oz broccoli with 1 tbsp grass fed butter - 250 calories (100 calories from butter)
3/4 cup walnuts - 375 calories
1 can of sardines in EVOO - 150 calories
All the black coffee you want and all the water you can drink
Protein g - 12 walnuts, 22 bone broth, 12 brocoli, 18 from sardines (64 total)
Fat g - 12 from butter, 39 from walnuts, 1.5g from broccoli, 18 from bone broth, 9 g from sardines
Carbs: 8 from walnuts, 30g from broccoli,
Fat: 64% protein: 22% carbs: 14%
Day 2-5: 800 calories
Same, but reduce to ¼ cup walnuts
Walnuts optional on all days - probably better results without walnuts
Day 1: fat - 56%, protein - 10%, carbs -34%
Day 2-5 - fat 44%, protein 9%, carbs - 47%
25:35 - 27:00
Mike: To summarize: The macronutrient percentage for fat and carbs likely doesn’t matter, but the protein does. You should keep your protein intake somewhere around 7-10% of total carbs.
The overall benefits you’re going to get from an FMD, just to simplify is:
-all leading to increased longevity…….unless you get hit by a bus. So, try not to get hit by a bus.
Jody: Cool. Those are pretty specific instructions. So, I’m going to do this for 5 days and then what do I do the other 25 days. And I’ll get blood tests at day 1, day 5, and day 30, right?
27:00 - 28:45
Matt: Yep. Come to the clinic and we’ll hook you up. And you probably need to take a month between each 30 day test to get back to your baseline. That way we take the scienciness of this from a 1 out of 10 up to a 2 out of 10. Twice as scienc-ey if my unscientific math is correct. For the other 25 days you should eat normal, but time restrict to 8 hours. Noon to 8pm as your eating window. That work for you?
Jody: Yeah, I can do that. What about other people listening to this. Should they do this? They should probably consult their doctor, right?
Matt: Sure. Or don’t. Honestly, that statement you see on everything of “consult your doctor” annoys the crap out of me. It tends to imply an all knowing doctor that just doesn’t exist. I mean, if you’re sick in general, have a physician you really trust and really knows you and stays super up to date with this literature, then great. Go for it. But I know lots of doctors. And I know lots of non-doctors who just keep up with what’s new. Medicine in general is always at least a decade behind the latest research. So, someone who cares, and reads can be just as informed as a doctor. So, never trust someone just because they’re a doctor. I know this will be unpopular with other doctors, but I’d say 95% of what I know and believe I know despite my medical school training. They told us that 50% of what we learned in medical school is probably wrong. In my experience over the last decade I’d say that’s gross underestimation.
28:45 - 30:05
Mike: Come on, I think you’re doing two things here. First, you’re underestimating the number of doctors out there who really care and keep up with the literature. And you’re overestimating the number of informed patients out there who are going read 100 books and 1000 articles per year like you and I do because we love it. Most people just want to be told what to do.
Matt: Ok, you’re right. I just don’t want people to give doctors too much credit. The M.D. behind the name means nothing. Ask your doctor what their favorite books on nutritional science are. If they rattle off 4-5 immediately, then take their advice. If they’re obese and can’t name 1, then please go to someone else, or do the research yourself. That’s all I’m saying. Also, if you’re going to do a straight water fast, then I’d say you do need medical supervision. Labs, monitoring, etc. Fasting isn’t dangerous, but like anything, the more hard core you go on it, the more risks there are that come along with those extra benefits. I think if you’re doing this FMD protocol, this is going to be safe for 95% of people who are healthy, not pregnant, etc. If you’re nervous, sure, consult your doctor. Also, this isn’t medical advice. I’m talking to Jody only here. This is informational only. I’m talking to you, lawyers out there.
30:05 - 31:00
Jody: Cool. So, what if I want to eat optimally those other 25 days? What type of diet in general should I do? And any drugs I can take to live forever?
Mike: Ha! Do you have a few more hours? Matt and I can debate the merits and pitfalls for keto, paleo, vegan, etc. Matt, what’s the most optimal diet?
Matt: Yeah, let’s actually tackle that in the next podcast. I know we both have some pretty strong beliefs about that. I think we agree on 90% of things, but it’s really fun to argue the the finer points. In general Jody, do this:
As Michael Pollan says in the Omnivore’s Dilemma: Eat real food, mostly plants, not too much. And as a nice heuristic to use, don’t eat it if your great, great grandmother wouldn’t recognize it. So, nothing out of a box or wrapper or with a list of ingredients you can’t pronounce.
31:00 - end
Mike: I can get behind that. Would love to hash out all the controversy around saturated fat, cholesterol, gluten, dairy, and dive deep into personalized diets based on genetics.
Matt: I can’t imagine anything more fun. And, yeah, the pill question. That’s gonna take some time. We’ll dive into that also. And while we’re at it, we should talk about the other things that may increase lifespan and quality: specific molecules (aka drugs), meditation, exercise, etc. Those things deserve their own specific podcast, though. For now, “let food be thy medicine”, Jody. Master that, and we’ll talk about some next level stuff just coming out that may have a really profound effect on longevity. I’ll bring you the food for my part of the experiment. That’s the stuff I eat every day, so I’m stocked up at all times with those things. Why don’t you take some before and after shirtless pics doing those super sexy poses people do in magazines. I think you’re gonna get some good body comp results.
Mike: And the Prolon goods are in the mail from me.
Jody: Can’t wait. I’m on it.