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A very small and preliminary trial found that treatment with growth hormone and two diabetes drugs (metformin and DHEA) was able to boost immune cell count, regenerate some of the aging thymus gland, and reverse epigenetic aging by 2.5 years in older men.
White blood cells mature inside the thymus and then become specialized T cells that help the body to fight infections and cancers. However, the thymus gland starts to shrink after puberty and becomes clogged with fat with age.
Some human and animal evidence suggests that growth hormone may regenerate the thymus. However, growth hormone also promotes diabetes so two diabetes drugs were used in the small clinical study.
This was a VERY small trial without any placebo controls so the only conclusion that can be made is that a much larger controlled trial needs to confirm these results.
@rhonda this is a really poor study. Or at least the conclusions drawn from it and trumpeted through the media are poorly supported by the study.
Take a look here:
Basically the ability to do some number of push-up stratifies the firefighters into age groups. When age is accounted for there is significant differences between only two groups. This presumably disappears when smoking is taken into account since the authors didn’t do that test. (Although they did collect the smoking status of the participants.)
Yeah as I looked closer at the study I see some of the analysis did not account for all confounding factors. It is always difficult to establish causation with these types of studies and statistical adjustment for age and BMI suggested that some of the risk reduction seen with higher push-up categories was accounted for by these characteristics. Also, the study assessed the association between push-ups and cardiovascular disease events. These results do not support push-up capacity as an independent predictor of cardiovascular disease risk. However, a higher level of muscular strength has been associated with lower cardiometabolic risk independent of cardiorespiratory fitness in other studies. Muscular strength has also been shown to have an independent protective effect for all-cause mortality and hypertension in healthy men.
I think the bottom line is it doesn’t hurt to do your best to stay fit and try to crush it with your push-ups!
Okay, I just tried it. No metronome, so I don’t know if I was keeping pace. (80 beats per minute). I got 33 with my back flat, touching the floor each rep. I’m 56, non-smoker. No history of firefighting…
For most Americans, due to all the costs, this protocol will be out of reach. The sample size all this is based on is very small and I am not totally convinced it will work. However, the marketing is very well thought out. It is a shame when so many folks are dealing with this who are on fixed incomes can’t access these recommendations. Especially since Mr. Geffen has been funding this researcher! I don’t really see any reviews from patients or their families either which is odd. This information has been out for what 2 yrs now and just now hearing about it. If it was such a slam dunk then why hasn’t some group offered to buy the protocol to make it free to all those who need it? Instead it has been sold to a health care marketing company. This health group has bought it and has created this pay to play setup and part of the deal is as more is learned you will learn so there is a monthly subscription which means they haven’t figured it out! You have to pay $1400 or rather $1399 for one time fee or monthly fee and it gets confusing as to whether they will do that for U.S. patients. Then you have to find a doctor locally who has signed up with them to access their software, if not they can have a tele doctor help you. I wonder what fees the doctors have to pay? Then you have to pay for labs and they won’t know what all the costs for those will be but it sounds like it can be expensive and my guess is your insurance may not cover them since it is probably still considered experimental. It also sounds like your insurance is not going to pay for the 2 hours for the doctor visits much at all. Then you have to meet with the doctor maybe 3 times a year. I just bet they will use the data from these participants to support their protocol and the participants will be paying most of the on going research or their insurance will if they are really lucky. It seems rather one sided. It feels a bit scammy. You would think, if in fact this protocol is the best cure for Alzheimer, that this would be shared world wide for all doctors to implement to patients much like so many other cures that impact a majority. Maybe have the NIH collect the data like The Human Microbiome Project. They can’t go there yet or ever and that is why this is being doled out the way it is. This makes me question Rhonda’s role in this. I see her tests show she has some genetic leanings for one type of Alzheimers and well she is all in … just in case. She promotes him but has she seen any improvements in xrays of her brain or something? I was hoping that Rhonda was a good source of information but I am now a bit skeptical of her approach and whom she is promoting. For years we have watched these types of sites and each time we are hoping maybe this will be the site that is not just marketing but actually promoting sound and ETHICAL science for human kind not just how much profit can be made. Sadly, as we all know so many take tidbits and exploit them as marketing tools with online heath sites. Is it no surprise so many have become jaded by such sites. Robb Wolf comes to mind with his fancy talk and all the holes in his stuff. The list goes on and on.
Hi! This was a big comment, but I’ll do my best to at least address a few points.
First of all, and most importantly, I bear no affiliation or financial ties with this episode’s guest or their work. My motivation for having Dr. Bredesen on the podcast is because I value what he’s doing and think it offers value to this community. Judging by the overall reception, thankfully, I think quite a few people agree!
You’ll notice that while I have linked to the company that offers the protocol within the show notes, in the episode itself it’s almost an afterthought. In fact, there are many things shared in the video (e.g. the broad strokes of some of the important biomarkers and even their desired ranges) that should be reasonably useful to a person that may or may not ever go through the official channels to use the protocol.
I think any sort of suggestion that the episode is an infomercial is a vast misrepresentation of the actual content, especially with the effort my team and I put into documenting the literature being referenced.
This point aside, you seem to have two other primary concerns, the first of which is efficacy and the second is the cost of participating in the protocol, which may involve an expensive baseline billed directly (but only if it’s not covered by insurance).
As for efficacy, I think it’s obvious these are still very early days. Again, there’s transparency to some degree about this in the episode (especially when we talk about the 2014 MEND and his upcoming paper that represents a larger number of patients) — in retrospect, it might have been useful to have a more fully formed conversation about that. Needless to say, I still don’t think it’s good cause to be dismissive.
In particular, I admire the gestalt sort of approach of the Bredesen protocol, because, while the individual “weight” of some of the interventions he’s focusing on may, I expect, be re-tuned from time to time to great a more targeted impact, it’s obvious that making an honest best effort at taking everything that’s known at a mechanistic level about Alzheimer’s specifically (and better aging generally) and weaving it into an approach that is immediately usable for those of us at risk presents some value. That’s probably the best you can get at this stage. More importantly, he’s even set up the infrastructure to allow that to happen under the care of a healthcare practitioner.
In many ways, that’s amazing! Turning early research into something clinically useful is a feat in and of itself, but even more so when you take into account that it’s entirely at odds with the way healthcare usually works. You may be met with pushback, for example, if you ask for a follow-up hemoglobin A1C just three months after having had one in normative ranges.
In the episode, you will hear Dr. Bredesen making this point in a variety of ways, talking about how he believes certain important biomarkers represented as within normal limits are actually not optimal or how some forms of insulin resistance may not be peripherally obvious.
I think anyone reasonable (even amongst the professionals) will be able to follow that as being a perfectly logically coherent thought, but without being able to justify the cost to insurance, they probably have trouble continuing to try to optimize on numbers that are otherwise within normal limits. At least that’s my impression from my own interactions as an otherwise healthy but prevention concerned consumer of the healthcare system.
One of the ways around this “systemic glitch” is probably to establish a baseline with a wide array of tests via direct to consumer tests — ones insurance may be hesitant to cover in some cases — and then work on the problem areas once they’ve been identified and may be easier to justify. In other words, exactly what the company Dr. Bredesen is partnering with seems to be doing.
This is obviously not perfect since it may ultimately mean not everyone will be able to access the care in the same way, but, hopefully, as future clinical success translates into more published case reports the tide will turn and prevention will become a prime mover rather than an afterthought. In general, though, I think it’s a pretty good compromise they have going with the current situation and still, in the worst case, a lot cheaper than even a few months of memory care.
You wrote, “More than 75 million people in the US carry at least one allele for apolipoprotein E (APOE), the major genetic risk factor for Alzheimer’s disease.” Don’t you mean APOE4?
Corrected it. Thank you!
This may be of interest to you. Suppression of CX43 is countered by Sulforaphane, thus preserving chemosensitivity.
I would like to know the benefit correlation between mice and humans.
If this diet allows a mouse to live 20% longer could this help a human live 10% longer.
Agreed. Keep in mind that a 48 hour fast in mice results in a 20% reduction in body weight whereas it results in a 1-2% reduction in body weight in humans. Perhaps a stricter TRE plus prolonged fasting in humans may move the needle a little more…
A news report about this paper was posted to Steve Gibson’s grc.health news group. Although it has this undercurrent of “auto-immunity”, it doesn’t really seem to be about that. Or at least not in the typical sense one sees the immune system invoked.
This appears actually to be a metabolic hack that involves triggering a set of immune cells in the blood of T1D patients given the vaccine to use glycolysis non-aerobically in non-hypoxic conditions. That is, “aerobic glycolysis”. These cells then apparently become a sink for sugar, fermenting it to lactic acid or otherwise shunting it off into other pathways. As a result the T1D patents given these vaccinations dropped their A1C’s from 7 to 6.
A few oddities about this process. (1) the drop in A1C occurs 2-3 years after the vaccinations but then seems durable – still in effect 5 years later and (2) it doesn’t impact the production of insulin by the pancreases of the patients. The patients are still diabetic, they just have better blood sugar control.
If you go into the paper understanding that it really is a metabolic hack that causes the drop in A1C’s it is much easier to understand. That said, BCG vaccination has also been used to treat a type of bladder cancer and multiple sclerosis. The latter presumably must be through actual immuno-modulation, right?
Super interesting. Thanks for posting this.
Yes, you are welcome.
Actually I haven’t been able to find any other person who found this interesting. No one I’ve told at work (largely research biology professors) nor anywhere else.
Just more indication to me of how weird biology is. Always something coming out of left field to surprise you.
Also the fact that these guys did an 8 year study when the end point they were looking for (restoration of pancreatic islet function) never happens. But they doggedly must have persevered tracking down the source of the 1 point drop in A1C that they did see.
From the paper:
“Cellular quiescence is a crucial process for maintaining the stemness of embryonic stem cells (ESCs) through inducing autophagy. We did not show sufficient results to prove β-HB induces autophagy and autophagy-dependent cellular quiescence (An et al., 2014, García-Prat et al., 2016). However, we predict that β-HB can induce autophagy in vascular cells, as well as ESCs, based on our observations of AMPK activation and mTOR inhibition by Oct4 upregulation after treating with β-HB in vascular cells. ”
@rhonda – is this enough to make you consider a ketogenic diet? Since I started ~8 hour TRE, I have no difficulty maintaining >2mM BHB fasted most mornings of the week.
I’m considering experimenting a modified ketogenic-ish diet with an emphasis on salmon, avocado, olive oil, nuts…as long as I can eat a lot of leafy greens and some blueberries.
I also seem to have no problem getting high levels of BHB with a 16-hour fast.
What concentration of blood BHB do you get after a 16-hour fast?
Leafy greens don’t seem to be an issue for me. I’m eating 2 large salads a day sometimes. I put lots of a salad dressing I make myself on them–just “O-live” olive oil (~80%), Braggs ACV (~20%), sweetened with some raspberry stevia.
Although these nutrients protect our eyes from macular degeneration it looks like they may do a lot more than that. I have read a couple of other articles about these 2 nutrients they may slightly reduce anxiety and improve sleep quality, just what we needed more reasons to eat our greens !
Yep! They accumulate in the brain and multiple studies have linked them to cognitive function.
So, I have found salmon roe at whole foods, but sprouts doesn’t have it. can lumpfish be used in a pinch? I only ask because not everyone has a whole foods near them. and most grocery stores do have the lumpfish caviar
Lumpfish roe is actually a great source!
It would be good to see Rhonda’s view on this, I’ve noticed a number of studies on mice with ketogenic diets that come to the same conclusion as this study. The key failure point for me is that fat is not a natural diet for mice, does the study have any relevance for humans or is it designed for failure?
@Magonrag @pmiguel There is a really interesting phenomenon that occurs in rodent studies given a ketogenic diet. Many of them tend to overeat unless they are given a calorie cap. In the literature, mice given a ketogenic diet that are allowed to eat ad libitum will develop obesity and metabolic problems. Mice that are fed a ketogenic diet that has a restricted calorie cap actually have improved healthspan and lifespan. I discuss this with Dr. Eric Verdin. I do not understand why rodents are not satiated on a ketogenic diet.
Thanks for the link Rhonda, I really appreciate your work.
@rhonda @Magonrag Yes and if the “KD causes T2D” meme was based on this phenomenon I would have some sympathy for it. But it is typically based only on the fact that a perfectly healthy animal in ketosis will be insulin resistant and eventually undergo some atrophy of its Pancreatic islet beta cells. But this atrophy and the insulin resistance is easily reversed by eating carbs for a few days as demonstrated here:
So Magonrag’s initial link was just someone click-baiting the internet.
The paper referenced by the medicalxpress.com article doesn’t come to the conclusion that the click-bait title suggests.
I have seen another rat experiment that did:
However it was based on the mice failing oral glucose tolerance tests and showing atrophy of pancreatic beta cells after being on a KD. It’s conclusions generated a rebuttal:
Irritatingly, the rat paper did not cite a previous study in mice showing the same effect. Perhaps because the study in mice showed that all the “T2D-like” symptoms were reversed when carbs were added back to the mice diets:
So the T2D diabetes that one gets from a KD can be reversed by eating carbs for a few days. Not really an issue, is it? The only real danger there is that you might fail an OGT test if you had been in sustained ketosis for a sufficient period of time–an issue frequently mentioned on ketogenic diet sites.
Can you provide the full reference for Dr. Pandas article showing the 28% lower body mass and 70% lower fat mass with time restricted feeding please?
Can you also confirm the duration of the experimental protocol (e.g. 4 weeks, 8 weeks, 12 weeks ect.)
Great podcast by the way!
Here is the full reference for those data.The experimental protocol lasted 12 weeks. Hope this helps!
Oh….mice, not humans then?
Is there research in existance related to the alternative of utilizing a sauna suit, (Kutting weight neoprene suit) during exercise instead of utilizing the sauna post or per workout. I realize the relazing effects would be minimized but are the other correlated benefits still in effect, heart health, heat shock proteins, etc… Basically, can a sauna suit be replaced with sauna use to raise body temp if a sauna is not available? I am not looking to lose weight with the suit but to gain any benefits through sauna replacement.
I cannot say for sure but I do think that the heat stress is the most important factor here. Other modalities of heat stress including hot baths, steam showers, hot yoga and perhaps a sauna suit seem likely to have an effect.
I would love to know if any of the alternative sauna technologies have any potential. Many people (myself included) don’t have access to a true sauna.
Love this site and the info provided, keep it up!
I think the heat stress is the most important factor. Hot baths, steam showers, hot yoga, and, of course, saunas.
Hello - I’ve been searching everywhere for information on (FIR) Infrared Saunas - I can’t tell if its fad or effective/comparable results to steam saunas. Any thoughts or links to more info?
Most of the research showing benefits of sauna use on the heart and brain are using traditional hot saunas that can reach a temp of 180F. The FIR saunas do not get this hot. the key is heat stress and perhaps staying in the FIR sauna longer may get you more heat stress. Personally, I prefer traditional saunas over FIR saunas.
I believe that the earlier HIIT studies did show that there were some people that were not genetically capable of improving their insulin sensitivity using this type of exercise. This experiment was done in England.
Can you link any of those studies? I’m not finding them and am super interested in what SNPs may regulate this. Thanks!
I’ve purchased Thorne Research Nicotinamide Riboside - each capsule is 125mg and it says on the packaging to take one a day or as directed by your physician.
I train 3-4 times a week, non smoker, healthy eater - mostly - 5ft 2 and 50kg.
Would you say 1 cap a day is enough or should I be taking more in order for this to have an impact?
This study found a dose of 250 mg was shown to increase NAD+ levels by 50% in participants…a dose of 500 mg raised NAD+ levels by 90% after 4 weeks.
Thoughts on the effectiveness of Elysium’s NAD+ product Basis?
The fact that Basis was used in the recent randomized controlled trial published in Nature showing that it increased plasma NAD+ levels in a dose-dependent manner suggests that it is effective at raising NAD+ levels in the plasma. This does not necessarily suggest that other brands are, strictly speaking, in any way inferior… but the fact that they have data showing the effectiveness of raising NAD+ levels published in a top-notch science journal is definitely a quality signal in my mind.
Thank you for responding and the link to the trial!!!
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