Calorie Restriction, Eat Once Every Other Day (EOD Diet)

To be clear, you're going to take your current weight stable calories/day, maintain them, but only eat EOD, INDEFINITELY? You will disappear, won't have much left to even draw blood for epigenetic testing. Or EOD cycling and re-feeding to maintain weight? I do strongly believe diet and fasting protocols do indeed lower epigenetic age. I've done a deep dive on ketones, I believe they are an anti-aging signalling metabolite. And extended fasting has vast amounts of pro-longevity research. I've been strict keto 5 yrs, and OMAD (one meal a day) for last 3 years. OMAD is not easy, would try that first, but having done it for so long, I could see myself reaching to EOD, but would have to double my current one meal bolus of calories on feed day to maintain weight. That's a lot of food to eat in one sitting! And I won't sacrifice muscle whatsoever in my protocol, so I maintain calories and do daily resistance exercise. After my initial rapid weight loss on keto, I've been weight stable (+/- 2-3 lbs) for years, with slight creeping up in weight as I continue to build muscle. To maintain weight, I cut back calories slightly, trading residual body fat lowering for muscle build gains (getting leaner but more muscular). But if you're not doing any resistance exercise, I believe your fasting protocol will likely consume into some of your skeletal muscle. I am 56, so maintaining muscle and preventing frailty is a goal of my overall anti-aging protocol. Building muscle has it's own pro-longevity signalling metabolites; for a separate thread. Have you read about Longo's FMD protocol? Longo is a leading anti-aging/cancer fasting protocol researcher. Or 5 day water only fasts?

https://johnalexanderblog.com/diy-fmd/

https://thequantifiedbody.net/fast-mimicking-diet/

https://prolonfast.com/pages/fasting-mimicking-diet

https://thequantifiedbody.net/5-day-water-fast-results/

Jimmy, you replied, but for some reason, it didn't populate the forum? I am taking the liberty to post your reply, and then I follow with a reply below.

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"@MAC Good point that I would disappear without anabolic activity from eating foods.  In that case, I suppose I would try and do the EOD diet until my BMI would be 18.5.  Currently, my BMI is 22 so I'm not too far away.  Once that is achieved I would want to maintain muscle mass and may end up doing the OMAD if it drops below 18.5.  One thing I noticed is that if one intakes apigenin one's muscle mass would sustain.  So I may keep doing that by drinking chamomile tea, which is great because it is zero carbs.  Reducing epigenetic age takes more than 6 months.  So this intense diet would have be sustained to signal epigenetic age reduction.  I would probably have to go as long as 6-9 months and get measured again.  That's a long time, and it may not work.  😂  But, the first step is mental and I would have to find other things to think about besides food.  
By the way, I don't believe in water fasting.  Most studies that improved health indicators involved CR and not water fasting.  CR works for sure.

I've read Dr. Longo's book.  And I just ordered a Prolon kit.  However, I do not believe Prolon would work for me because the soup packets contain carbs.  We will see though when it arrives and I test my blood sugar after ingesting it.  I do not want to see my blood sugar spike.

Anyways, I am thinking about starting OMAD and going from there...still hyping myself up for it. :-)"

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OK, you are going to go into a negative energy balance until your BMI drops to 18.5, and then what? It won't take long to drop to 18.5 from 22, on EOD, constant calories. Then how are you going to keep generating this "anti-aging" CR signal? Unless you are keto (best at preserving muscle at expense of fat) AND doing some pretty intense total body resistance exercise, you WILL loose skeletal muscle on this journey. Show me the science/paper on taking "apigenin" preserving muscle mass on a negative energy balance diet, that is, on a weight loosing diet? The only way to BUILD muscle is with anabolic resistance exercise...amino acids DO NOT build nor prevent muscle loss on a negative energy balance calorie intake diet, only resistance exercise can (Blagosklonny). To generate your epigenetic anti-aging "CR" signal , you will have to undertake some type of fasting protocol, yet "preserve" your functionality/resilience/anti-frailty. Unless you have some physiology lab at your disposal, I think only a series of total body muscle pictures before/after can assess your skeletal muscle changes as you drop BMI. 

Do you have references on OMAD/epigenetic age in humans?

In regard to OMAD not being "as fast" as say some other more extreme protocol, the key is to maintain the biggest epigenetic signal you can sustain over your lifetime, not just 6 months. Even Longo's FMD, does one have to maintain this INDEFINITELY to do a reset, autophagy, and lowering senescence? What happens if you abandon it after say 1 yr, do you loose the epigenetic gains? I am not sure what I would consider next beyond OMAD as a normal routine. Going EOD, I think I could do it having done OMAD. I could imagine consuming double the meal EOD as current OMAD, but I cannot imagine sleeping that night if current dinner was my meal, unless I took the meal say at lunch.

I'd like to see Longo's data on true long term calorie deficit and muscle maintenance. His longevity diet specifically recommends higher intake of protein to maintain muscle mass, in an isocaloric maintenance scenario, not calorie deficits you are planning. I disagree that it's the nuts and olive oils (10 grams of nuts he recommends is meagre protein, and olive oil has none)...nuts possess relatively little amino acids needed for complete  muscle protein synthesis. Walnuts have only 15% protein, and it's PLANT protein, typically much lower in the key BCAA's for muscle protein synthesis. In his mediterranean centric diet, one would need legumes and higher protein carbohydrates to maintain muscle outside of animal protein.

Thank you for sharing the apigenin paper (on mice, not humans). A relevant passage, my highlight.

"Results of hematoxylin and eosin (H&E) stains of quadricep cross-sections confirmed that apigenin increased muscle fiber size. The weight of the tibialis anterior, gastrocnemius, and triceps muscle were not altered by apigenin.  Apigenin did not significantly affect total body weight"

So very muscle specific, and what about the hundreds of other muscles, and translation to HUMAN? And these mice were fed ad libitum on a standard diet, NOT EOD. You are proposing SIGNIFICANT calorie deficit, and you expect this molecule to save your total muscle profile? 

Would love to follow your n=1 guinea pig experiment on this molecule during your fasting journey, without resistance exercise as done in the paper.

Many doctors and dieters say that interval fasting does not help the body shed excess fat. Starvation or irregular meals can slow down our metabolism. It reduces the rate of weight loss. Even though you will consume fewer calories, they will not be processed as quickly as if you were eating six meals a day, trust me. However, there is a way to fix this. If you want to stick to interval fasting and only eat once a day: try taking fat burners. I read about the usefulness of fat burners during weight loss and fasting here https://signalscv.com/2021/11/phenq-reviews-2021-the-best-thermogenic-fat-burner-in-the-world/. Of course, you can combine this with not too hard workouts.