#48

Better late than never….

Here are Dr Joseph’s answers to the submitted questions

Hi Joe,

Thanks for your patience here! Please see responses from Dr. Joseph below.

Any issues with a DIY low carb version of FMD (same calories by day but lower carb)?

  • FMD has 77 ingredients and researched for 13 years and $48MM. THis is because any variation of ingredient can cause cellular recognition of food or deprivation and both are not good.

  • Most people think that a lower carb version could be more ketogenic/better. We have tested a lower carb version and it turns out to induce less autophagy. Also lower carb risk hypoglycemia.

  • We priced the FMD to be at $10/meal which is the current amount the average American spends on food and added $25 for the supplements and beverages we supply. So ProLon/FMD are price neutral for most people and the DIY will cost you more (also time to buy food and cook) and will risk not mimicking the fast or hypoglycemia.

Wouldn’t those soups be super high-glycemic given the ingredients? (One listener said her CGM showed big spikes)

The soup carbs have been studied over 13 years and tested now in over 40 clinical trials. They are very carefully designed with precision nutrition to increase a bit of carb floating in blood and create a mini-insulin spike, two main components of feeding and protecting muscle and not getting into hypoglycemia. This is one of the secrets of the FMD which is NOURRISH the body, PROTECT/Grow muscle, FUND cellular Rejuvenation and is what makes it superior to water fast. The FMD today is not just a fast-like but is actually superior to fasting: microbiome of complex carb, muscle protection, boosting cellular rejuvenation and reprogramming, etc.

Carbs are not ‘enemy’ they are essential for life…we need the right amount, right timing, right composition and this is why you buy from our science.

Are the glucose spikes a feature or a flaw?

They are a main feature of the success of the program. Without the mini-spikes of glucose and insulin, you lose muscle and slow metabolism. This is why most diets and GLP-1s induce muscle loss, decrease in metabolic rate and ultimately fail after a few months. The FMD nutri-technology goes as far to nourish/protect muscle and newly rejuvenated/reprogrammed cells while keeping deprivation signals on fat. A win-win, that with water fasting or GLP-1 is a lose-win!

FMD has now 134 granted patents and successfully tested in over 40 clinical trials. One of the trials was about a lower carb version and did not perform as well as the current ProLon version.

How about Prolon with a GLP drug to take away the hunger aspect during the fast. This would make the fast SO much easier, but would the increased insulin output caused by the GLP drug interfere with the putative benefits of the FMD?

We recommend you do ProLon instead of the GLP-1 so that you protect muscle, lose visceral fat, rejuvenate the cells, all features that the GLP-1 does not provide.

GLP-1s are a deprivation, like calorie restriction, of the body but even worse they are carried by a biologic which has side effects such as muscle loss and cancer risk.

For some who are very addicted to food, need to lose weight fast, some doctors put them at a 50% dose of GLP-1 and FMD. Patients in this case have lower appetite and therefore can comply easier on FMD. Many doctors then wean off the GLP-1 so that the patients stay on FMD which is much healthier in the long run.

All organs and tissue shrink while doing FMD in the words of Valter Longo. Why not muscle too?

Because FMD/fasting works by stress and not deprivation, Growth Hormone, a hormone of stress, spikes and activates muscle growth. Since FMD includes carbs and protein, muscle is maintained with it. There is a transient phase where muscle consumes its glycogen reserve so it seems like shrinking but it is not.

From a forest view, when our ancestors did not have food, the body learned how to transform fat into ketones to nourish the brain and stay awake to seek food and increase Growth Hormone to protect the musculo-skeletal system to keep walking and find food.

Common issues people would have encounter when trying to replicate using home cooked meals?

They and all the hospitals that tried do not get the results of the FMD and end up buying Prolon, especially when they realize the complexity of the balance between mimicking fasting and protecting from hypoglycemia and the precision formulation that takes 16 suppliers to produce a proLon box. Also important to mention that Prolon price per meal is not at or shepherd than cooking at home and buying drinks and supplements.

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Is there an alternative to Prolon 5-Day Fasting Mimicking Diet (FMD)
#49

He’s clearly very anti-GLP1, but I don’t think there’s evidence of these meds causing muscle atrophy over and above what you’d expect from caloric restriction, protein restriction and lack of resistance training. If anything, I’m reassured that taking a GLP agonist with FMD should work just as well and be a lot less miserable with the added hunger suppression.

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#50

I agree, the statements on GLP1’s are misleading, and can mostly be true if the GLP1s are misused and too rapid a weight loss occurs, which will target muscle. But work out, and lose 0.5-1 lb per week (no more) until IBW then back off to minimum dose to maintain has improved body composition, including visceral fat.

The claim of GLP1’s causing cancer is a bit misleading. I’ll go with vera-health.ai with this:
The question of whether GLP-1 receptor agonists (GLP-1 RAs) cause cancer is complex and has been the subject of extensive research. These medications are primarily used for treating type 2 diabetes and obesity. Concerns have been raised about their potential link to certain types of cancer, but the evidence is not definitive.

Thyroid Cancer: Initial concerns about an increased risk of thyroid cancer, particularly medullary thyroid cancer, were based on rodent studies. However, human studies have not consistently shown an increased risk. A study suggested a higher risk of all thyroid cancers after 1-3 years of treatment with GLP-1 RAs, but the evidence remains inconclusive, and the risk appears more evident in animal studies than in humans 21.

Pancreatic Cancer: The relationship between GLP-1 RAs and pancreatic cancer is also debated. Some studies have reported a decreased risk of pancreatic cancer among patients using GLP-1 RAs compared to other anti-diabetes medications, especially in those with obesity and tobacco use disorder 8. However, concerns about potential pancreatic carcinogenesis persist, necessitating further investigation 1.

Breast and Colorectal Cancer: A systematic review and meta-analysis concluded that GLP-1 RAs do not increase the risk of breast cancer 1. Additionally, GLP-1 RAs may be associated with a lower risk of colorectal cancer, as suggested by studies in patients with polycystic ovarian syndrome 11.

Overall, while some studies suggest potential associations between GLP-1 RAs and specific cancer types, the evidence is not conclusive. It is crucial for healthcare providers to monitor patients using GLP-1 RAs, considering both the benefits and potential risks, and to engage in shared decision-making with patients regarding their treatment options. Further research is needed to clarify these associations.

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#51

A lot is based on the supposed benefits of IGF-1 suppression being good for longevity. Are we sure about this? Doesn’t Ghrelin (produced by hunger) increase both GH and IGF-1? Maybe the wrong lessons have been learned from IGF knock out mice.

Here is an alternate view:

Insulin-Like Growth Factor I Prevents Cellular Aging via Activation of Mitophagy

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#52

Thanks Joseph_Lavelle for posting Dr. Joseph’s answers. He clearly does his job of supporting the product, some of his points are indisputably true, like Prolon being a standardized, FDA-approved method, backed by extensive research. I have some counterarguments to express though.

I think the cellular recognition point is exaggerated, for many reasons. Whereas food deprivation is more sensible, up to a certain extent. The truth is that the product must have some shelf life and must be standardized to be FDA-approved. Eating natural foods with strict adherence to calories and macronutrients should conceptually ensure the same effects. At least, my experience in using natural foods was such.

Autophagy: Valter Longo in his latest podcast (discussed in another thread) played down the role of autophagy, also stating that autophagy kicks in only during the 5th day of the FMD, at the end. So, this argument would not appear to have preponderant significance. In another podcast (I listened to all the available interviews with Longo), VAlter affirmed that a keto FMD would probably be closer to a true fast, but that the content in carbs was mean to avoid hypoglycemia.
My personal n=1 experience is that a person without diabetes or pre diabetes will rarely experience hypoglycemia.

No way the DIY version will cost more, it will cost much less. You can do it on raw foods and you can do it by cooking the bare minimum (for example, zucchini and carrots at the microwave).

I think the above is some truth mixed to salesmanship, especially the last part. I agree though on insulin spikes being useful to avoid muscle catabolism.

I wonder if the above is supported by evidence. How a 750 kcals/day (1150 on the 1st day) diet does not induce deprivation? How 23 grams/d of plant-derived protein can maintain muscle mass?
How can you say that exhaustion of glycogen reserves does not constitute loss of muscle mass? The bound water is lost, but AFAIK that is intracellular water. What Dr. Jospeh does not say is that muscle mass will grow back again usually, if proper refeeding is carried out.

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#53

What would be your scheme of combining FMD + GLP1RAs?

i.e., would you use GLP1RAs exactly in concomitance with the FMD, or start one or 2 days prior, and in which dosages, and ending when?
I too am interested, since the main obstacle to lifelong adherence is probably the difficulty in tolerating hunger and the perceived sense of deprivation. At least during the 1st phase of FMD.

Also, GLP1RAs are known to potentiate glucose-stimulated insulin secretion. Could this cause a risk of hypoglycemia episodes?

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Experience with GLP-1s
#54

Good question. I think hypoglycemia is rare with GLP meds (is this your experience with pts, @DrFraser ?), but might be worth wearing a CGM to be safe while doing FMD. Also good question about the protocol. I got appetite suppression within 24 hours of my very first dose of compounded tirzepatide (only 1mg), but dosage and timing of appetite suppression can vary quite widely from person to person, so it might take some trial and error if the plan is to only use the GLP med before FMDs.

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#55

I’ve got a lot of patients on a GLP-1, SGLT2-i, Acarbose simultaneously, who do not have T2DM. I’ve not had any get hypoglycemia. When Rapamycin is added in, this often makes blood glucose run a bit higher. Most of the time all 3 of these agents + rapamycin only has a tiny drop in HbA1C, often 0.3% drop.

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#56

It’s good to know that GLP1-RAs do not cause usually hypoglycemia in nondiabetic subjects, although in the context of FMD we have a situation of lowered carbohydrates and energy input, about 75-80 grams/d in days 2 to 5. It would sure be better, if using GLP1-RAs, to stick to the original macros and not to adopt a lowcarb variation of the FMD.

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#57

As part of the prolon facebook group, I see SO MANY people who are using prolon with the singular goal of losing weight. Many of those people don’t even know it’s for more than that *bangs head against the wall. (I haven’t been active in that group for quite a while and no idea if things have changed). I even have two friends who tried it with the same goal, all while having no idea it could be health promoting. Knowing that, it makes sense that he is a little triggered by glp1’s because they could put a huge dent in their business.

I’m the glucose spike person, and it was in no way a mini spike. Granted, I tend to spike more than most people, but it’s up there with the highest spikes I can get with anything.

Having said all of this, I am a prolon fan, but I wish they would be a little less sale-sy. They price it that way because they can, and that is fair. To say the supplements and tea are worth $25 is comical :slight_smile:

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#58

On second thoughts, if the effect size of potentiating glucose-stimulated insulin secretion is significant, it would be best to do the opposite, that is adopt a lowcarb variation of the FMD or alternatively to avoid simple sugar or food with high glycaemic load.

The concept is that if there is a large peak of blood glucose concentration, the insulin secretion will be overstimulated by the GLP1-RA, this means that the peak will become probably a trough, a significant one if the amplifying effect of insulin secretion is strong. The final effect would be a hypoglycemic trough, potentially dangerous.

Bottom line, if the above reasoning is correct, if we use a GLP1-RA while doing a FMD, we should adopt the cautions T2 diabetics adopt, like monitor postprandial peaks and avoiding troughs. By CGM or strips.

Another thought is that the Prolon package contains some foods with potentially high GI (chocolate bar, soups…), if so it would not be suitable to use in conjunction with GLP1-RA .

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#59

FMD #2 has begun

I’ve been sitting in my latest kit for a month because I just couldn’t break my latest addiction to Dr Jackson’s overnight oats (with green tea) / chia / flax / walnuts / Greek yogurt.

But I finally got tired of the love handles I grew over the holiday’s. So today I started.

I had forgotten about the restriction on caffeine. I’ll honor that rule with some regret but also some hope that I can sustain it after the 5 day FMD. I previously stopped the coffee to focus on green tea. But only 2 cups of green tea per day doesn’t sound like enough.

Updates;

Day 1: I wasn’t hungry per se but the extra adrenaline made it hard to focus on anything. But I slept great!

Day 2: I must be into ketosis as I am not hungry. I am okay with 2 cups of green tea now that I found the hibiscus tea. It’s wonderful. I look forward to another great sleep. Still struggling to focus but it’s better on day 2. I love the bars in the kit (macadamia nut plus). Of course everything tastes great when I’m starving, so YMMV.

Day 3: So then I decided I could do a spin class and then do a full body weight lifting workout and then sit in a 185f sauna for 25 minutes while doing a FMD. That was a hard day. I had to keep telling myself if was only every 3-4 months. I survived.

Day 4: I turned a corner. I awoke to feeling contentment. I ate my bar slowly (to stretch the pleasure) but didn’t feel hungry before or afterwards. I am also past feeling deprived of caffeine. I’ll try to stay at this low level (2 cups of green tea per day) indefinitely.

Day 5: Finish line in sight. So of course I lifted upper body and did sauna last night, and then did spin class plus lower body lifting plus sauna this morning. It was a hard day but I’m going to make it. I had an extra cup of green tea to avoid falling asleep at work.

The body aches and recovery speed is already better. My HRV is much higher and my RHR is back to my old 40-41 bpm. Now that I’m stable at a very low calorie intake, I’m planning to shift my diet a bit to reduce overall calorie intake and reduce protein further (started at 200g/d 6 mos ago) by reducing / dropping regular dairy. I may also start eating very small dinners as I have been doing during the FMD. I’m going to aim for zero visceral fat (maybe that gets me to 10-12% body fat overall). I always worried that eating less would slow recovery / adaptation but I think I can come down some without that happening. I’ll see.

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#60

I lost seven pounds on the brand new Norovirus intervention. 5 days of poor appetite and 24 hours of colon prep like bowel clearing. This where the seven pound loss occurred. Small risk of death due to dehydration. Watch the urine output. It helped reaching my New Year resolution of getting under 150 lbs, at least for a little while.

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#61

@Dr.Bart its wise to look for the silver lining. The benefit of a virus is you don’t have to rely on willpower to stay on the diet.

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#62

If diet and exercise don’t work, that just leaves disease.

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#63

Valter Longo in FMD: cancer and metabolic disease

Hint: FMD is good, of course. Glucose spikes from FMD foods might be the key to reducing insulin resistance. FMD biggest impact is on unhealthy people. Lowering CRP, BP, hba1c (with repeated cycles).

No enhanced autophagy until day 5 during FMD

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#64

I don’t remember if I’ve already listened to it, but I’m going to put it in my watchlist anyhow!

Edit: yes, after a few seconds I realized I already listened to it and it also amazed me that autophagy takes so long to be triggered. On the other hand, Longo says that autophagy is not the most important thing to achieve for longevity.

I recently listened to a podcast with Longo in Italian. He wants to create his channel, I don’t know if in English, in Italian, or probably both.
What I remember well from this discussion in Italian is that he spoke about diabetes and FMD, it usually takes 6 to 12 consecutive FMD cycles, one each month, to obtain significant results in diabetic and prediabetic people. This from clinical tests.
I wonder though, one FMd per month, that would be ideal to be always metabolically healthy but in thin people, it’s going to affect muscle mass detrimentally.

In people who tend to gain weight, that would be the natural alternative to GLP-1R agonists, with no detrimental effects. Will power would be required though, a good dose of it.

I’m also partially convinced that one FMD per month would approach the effects of Rapamycin on mTOR inhibition, similar to a monthly intermittent dose, maybe triggering the upstream signals mentioned by Sabatini. Maybe. This is still a partially obscure issue.

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#65

I started following Longo in early 2020. I watched everything I could find with him and even read his book. I think he is quite excellent, but having said that, while he is a great scientist, he’s not an engaging speaker, so I don’t think he has ‘caught on’ as much as he deserves. And of course, some of the podcasters who were originally on board have since left to hop on the all the protein you can eat train. Seeing that made me wonder too.

I started doing Prolon once a quarter and did it for 3 years. I’d lose from 0-4 pounds each time, but I’d always immediately gain most or all of it back, possibly because my diet was already healthy and I only had a few pounds to lose? Because it’s designed not to lose muscle, and because I didn’t loose so much weight, I’m guessing there was very little muscle loss?

Over those 3 1/2 years, I lost aprox 7 pounds, and even though I have a box here looking at me, I haven’t been able to do one in a while because I don’t have weight to loose and worry about being underweight, even if it’s only for a week or two. Maybe it’s fine, but perhaps it wouldn’t be healthy.

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#66

Longo says there is no loss of lean mass using FMD. I don’t think I lost any lean mass (aside from waste and fluids) either time but I worked out rather hard.

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#67

I don’t use FMD for weight loss. I find it an effective immune system reset. Plus it breaks all my eating habits so I can reset them.

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