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At this altitude, I can run flat out for a half mile before my hands start shaking.
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Hello, my caribou and capricorn.
4:31
This is Tim Ferriss and welcome to another episode of The Tim Ferriss Show.
4:34
This episode is a repeat guest, one of the most popular, Dr.
4:40
Dominic "Dom" D'Agostino, known as Dom, of course.
4:45
Twitter, you can find him at Dominic D'Agosti2.
4:50
That is Dominic d a g o s t i the number two.
4:53
He is an associate professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida Morsani College of Medicine and a senior research scientist at the Institute for Human and Machine Cognition, IHMC, which also had a great treatment in the current issue of Outside Magazine.
5:12
On which there's a clown who looks a lot like me.
5:14
Uh he has also deadlifted 500 lb for 10 reps after a 7-day fast. He's a beast. Also good friend of Dr.
5:20
Peter Attia, who's also been on this podcast.
5:25
The primary focus of Dom's laboratory is developing and testing metabolic therapies, including ketogenic diets, ketone esters, and ketone supplements to induce nutritional or therapeutic ketosis, and low-toxicity metabolic-based drugs. That's a mouthful, eh?
5:40
Much of his work is related to metabolic therapies and nutritional strategies for peak performance and resilience in extreme environments.
5:46
This is where I get very interested.
5:48
I recently went up to altitude and used exogenous, not endogenous, exogenous ketones to help me acclimate and function at high altitude.
5:57
But it also works in the opposite direction, underwater for instance, both related to hypoxia.
6:02
His research is therefore supported by, among others, the Office of Naval Research, the Department of Defense, and other private organizations and foundations.
6:11
In this part three, Dom has been on twice before, Dom focuses on disease prevention, cancer, and more mastery of the ketogenic diet.
6:19
So, as I always say, without further ado, please enjoy this tutorial and masterclass with Dominic D'Agostino.
6:33
Okay, I covered the ketogenic diet and I covered questions about exogenous ketones, and that took about two hours.
6:40
So, now I'm going into cancer research questions, uh or just questions in general about cancer.
6:45
So, the first one I like to address, I've gotten many emails about this, um seen a few questions on on Facebook.
6:51
Does the ketogenic diet beat chemo for for all cancers?
6:54
And uh I would say absolutely not, but that does not mean that it should not be used uh as an adjuvant or a support for various cancer therapies that are out there.
7:10
Uh a number of situations where the ketogenic diet may not be the preferred therapy for most cancers.
7:15
I would say leukemia, lymphomas, Hodgkin's lymphoma, thyroid cancer, testicular cancer, uh if caught early, prostate cancer, melanoma, breast cancer.
7:27
All these cancers can be effectively treated with chemotherapy or radiation in some cases.
7:36
And also uh brain brain tumors, if it's if it's class one or two, tumor that's not a grade one and two, that's not very metastatic and it's more localized, then surgery, radiation, chemo can be very effective.
7:51
We focus on cancers that are not really treated effectively with the standard of care.
8:00
Brain tumors, grade four would be a glioblastoma cancer.
8:05
It it's highly invasive, highly aggressive, sort of has the a metabolic phenotype.
8:13
We say that that expresses the Warburg effect.
8:15
So, it's it's very glycolytic.
8:17
So, the name glioblastoma multiforme, it's it's comprised of very a very diverse, heterogeneous array of cells that are resistant to therapy and it's genetically very heterogeneous.
8:36
Metabolically, probably much more homogeneous in in regards to being able to to target it from a metabolic standpoint.
8:43
So, we focus on, you know, this aggressive metastatic cancer and brain tumors in our lab and we think the standard of care, we know that it does very little.
8:54
We do feel that the ketogenic diet, when properly administered, can dramatically enhance the efficacy of standard of care.
9:01
So, even though the standard of care may not buy much time for patient with glioblastoma, we think that we could dramatically enhance the efficacy and maybe reduce the the side effects of of standard of care with the ketogenic diet or maybe combined with intermittent fasting.
9:28
I would recommend looking at the work of Dr.
9:31
Adrienne Sheck and she's at Barrow Neurological Institute and she's done some studies with a preclinical mouse model of glioblastoma.
9:42
And that work has inspired a clinical trial that's now recruiting patients to use the ketogenic diet combined with standard care, which would be temozolomide and radiation.
9:53
And her work is is really remarkable in that it shows the uh the ketogenic diet dramatically enhances the efficacy of radiation therapy.
10:08
And it does that through a number of different mechanisms that she's looking at.
10:13
I think most importantly to highlight, if we kind of look at the the sum of all her work, which is a incredible body of work that that she's done.
10:23
She was working on this long before I came into the field.
10:24
Uh I was directed to her by Dr.
10:27
John Grow, who's probably the leading ketogenic diet researcher uh chair of pediatrics in in Calgary now, but he was at Barrow Neurological Institute.
10:37
And I contacted him and he directed me to Adrienne Sheck's work and it really blew me away.
10:44
She shows the the effect of the diet can be dramatically en- enhanced with radiation.
10:52
So, I was kind of a pretty critical of radiation therapy for cancer, especially for glioblastoma, uh for various reasons, but when looking at Adrienne's work and just hearing from you know, feedback from patients, my thoughts on radiation therapy have softened a bit.
11:13
And in the context of radiation therapy given with ketogenic diet, it appears that nutritional ketosis enhances the tumor-killing effect of radiation.
11:28
And it does that through a number of different mechanisms probably crippling or reducing glycolytic flux through the tumors, which would impact their antioxidant endogenous antioxidant status by reducing things like the pentose phosphate pathway, which helps the cell regenerate glutathione.
11:51
So, if um and we know that the efficacy of of the uh radiation therapy really results from generating oxygen free radicals in the tumor tissue.
12:04
And tumor cells are already at an elevated state of oxidative stress.
12:10
So, further stimulating uh reactive oxygen species production with um the damaging effects of radiation can put them over the the edge and be very destructive.
12:20
So, the ketogenic diet seems to enhance that process and simultaneously the ketones tend to lower inflammation in the normal healthy tissue and protect your normal healthy brain tissue.
12:34
We think that there's a lot of potential for the ketogenic diet as an adjuvant.
12:39
For all our studies, we've always used the ketogenic diet as one piece of a combined metabolic therapy approach.
12:45
So, the ketogenic diet is an adjuvant to you know, uh hyperbaric oxygen that we've used.
12:54
Um and now we're looking at, you know, ketone supplementation and combining that with hyperbaric oxygen.
13:03
So, the ketone supplements tend to further augment the therapeutic efficacy of the ketogenic diet by lowering blood glucose and elevating blood ketone levels.
13:13
That therapeutic zone that Tom Seyfried calls the metabolic zone.
13:16
The glucose ketone index is simply the the ketones the uh the glucose by the ketones.
13:24
An index of, let me see, or two.
13:27
Really an index of of one is what you want to shoot for.
13:31
And when you achieve an index of one, you essentially get a blood glucose level that's and blood ketone level that are essentially the same. So like 3. 5 millimolar.
13:44
A level of glucose and ketones that a person could sustain and would be sort of physiologically optimized.
13:52
He has a paper on that nutrition and metabolism describing the glucose ketone index and that has been thought to be sort of the optimal therapeutic zone for a person patient using the ketogenic diet to manage their cancer or combining it with the standard of care.
14:11
So it makes sense to use a metabolic based approach on tumors that have a Warburg phenotype.
14:16
So tumors that are highly glycolytic which include about 80 to 90% of cancers and the cancers that tend not to be the ones that are more glycolytic are also the ones that you don't have to worry so much about.
14:35
These are ones cancer cells that generally are not very invasive or aggressive in regards to growth.
14:43
The ones that are not glycolytic.
14:43
So cancer cells for example that wouldn't show up on a PET scan and that would be like prostate cancer for example.
14:52
Yeah, the ketogenic diet does not beat chemo.
14:56
It's we know that chemo can be effective for a number of different cancers and if caught early sort of a growing list of different types of cancers.
15:07
Ramsey Metcalf asked a question after listening to his chat on Dr.
15:10
Rhonda Patrick's show, I want to know more about the detoxifying effects of ketosis on pre-cancer cells.
15:19
And uh healthy individuals And how does one jump-start daily ketogenic cycle without supplements?
15:25
And how can you maintain lean muscle mass when fasting?
15:34
So, a number of questions there.
15:34
As I mentioned, I'll kind of talk about uh refer back to the metabolic zone, uh achieving the metabolic zone, a glucose ketone index of one or two.
15:46
So, Google the glucose ketone index and download that paper in nutrition metabolism.
15:51
It's open access and kind of gives you a description of where you have to be uh when you do fasting or the ketogenic diet.
15:59
And I think if you achieve that zone, I think that and you do that two or three times a year, that could be very therapeutic in regards to cancer prevention, really effective at targeting sort of precancerous cells, and maybe even jump-starting your immune system, making your immune system maybe more hypervigilant against the cancer cells that you already have.
16:25
So, as far as jump-starting your body into ketosis, uh you could use exogenous ketones.
16:31
Oh, okay, without supplements, you asked.
16:33
Uh jump-starting can be done with exercise.
16:35
I wouldn't recommend vigorous exercise.
16:38
I would recommend, you know, a walk, uh two three-hour walk, for example.
16:44
You might want to preface that with a short high-intensity 10-15 minutes or something to just kind of activate your sympathetic nervous system, but not too much.
16:57
Do some, you know, push-ups, chin-ups, a little bit of uh a few sprints.
17:03
I believe that when you activate your sympathetic nervous system, mobilize a lot of free fatty acids for fuel and set your body up for a more effective fat burning and more effective transition into ketosis when you do kind of a low a low impact walk.
17:23
Done a lot of testing on myself of glucose and ketone levels in different scenarios and that seems to work really well.
17:29
I did that yesterday actually.
17:32
So fasting can stimulate autophagy and perhaps you make the immune system sort of more more hyper vigilant against cancer and pre-cancer cells I mentioned, but you need to acknowledge that if you fast too long or you calorie restrict too long that can suppress your immune system.
17:52
Let me see, lean body mass.
17:52
So there's a couple ways to get around the loss of lean body mass that's going to happen.
18:01
You know, you have to realize that you're losing a lot of water when you do when you do a fast.
18:05
So your weight may go down, but a lot of it's going to be water weight.
18:08
You could probably mitigate some of the muscle loss with branched-chain amino acids.
18:16
And I would buy just a pure branched-chain amino acid product that's just branched-chain amino acids and nothing else.
18:21
Consume that sort of if you're going to continue doing any form of exercise.
18:26
I wouldn't recommend doing you know, high-intensity exercise if if you're fasting.
18:32
But if you do do any exercise, take your branched-chain amino acids before and maybe during.
18:38
It's important I always emphasize this when people talk about you know, wasting away when you when you fast and George Cahill's work at Harvard shows that the physiological shift that occurs when you're fasting, when you enter a state of fasting ketosis functions to have a really profound protein-sparing effect.
19:03
So your brain is highly metabolic organ and uh it's going it's a big glucose sink.
19:09
And when you elevate ketones, that prevents a lot of the gluconeogenic amino acids from being broken down in the skeletal muscle.
19:19
So, it's very protein sparing in that regard.
19:25
So, otherwise, right, if we fasted, we would rapidly waste away, uh probably within, you know, less than 2 weeks.
19:31
But, there's reports of people fasting.
19:34
There was a guy that's 500 lb that fasted for over a year.
19:38
And uh and there was no no major ill effects reported from that.
19:43
And he fasted down to 190 lb.
19:46
Some of the helpful supplements that I think you'd utilize during a fast would be, like I mentioned, branched-chain amino acids.
19:55
Um My good friend Layne Norton did his PhD on leucine.
19:58
And he did it in the lab with Donald Layman.
20:01
So, if you're interested in in kind of understanding anabolic or anti-catabolic effects of branched-chain amino acids, uh go on the PubMed and look up uh Layne Norton's studies on leucine.
20:14
You know, I've experimented with a few things.
20:16
I think the serotonin precursor, 5-HTP, can be beneficial.
20:21
If we're taking in branched-chain amino acids, we're actually limiting the transport of of tryptophan across the blood-brain barrier because it competes.
20:30
I I tend to get the munchies at night.
20:33
So, my appetite gets really high at night time when I was doing uh when I was fasting.
20:40
And I found that um and I fasted too with uh with branched-chain amino acids, but I think a supplement like 5-HTP at night may be able to uh to reduce some of the hunger cravings and also help put you to sleep.
20:56
So, if I'm hungry, I find it found it kind of hard to sleep uh after a while, then my my body adapted to it.
21:03
So, so, that product, uh ketones, MCT oil, and MCT oil powder may be helpful, but not absolutely necessary.
21:15
There's a book out there called The Fasting Cure by uh Upton Sinclair, and you just Google The Fasting Cure and Sinclair, and you'll find it, and it's a free PDF to download.
21:26
And it's a fascinating little book that just talks about the benefits of fasting.
21:34
So, next question is Lowell uh Kubic, and he asked, "In addition to an update on ketosis' effects on cancer, is there any updates with ketosis affecting chemotherapy recovery?
21:46
What types of cancers does ketosis have the largest impact on?"
21:51
So, I kind of answered that already.
21:54
Uh managing brain tumors and metastatic cancer, I would say would be at the top of the list.
21:59
And as I mentioned, as an adjuvant to chemo and radiation, see Adrienne Sheck's work at Barrow Neurological Institute, uh her preclinical work, and also in ongoing clinical trial.
22:13
And I would also encourage anyone, you know, who's really passionate about seeing this transition into the patient population, if you know, if they're interested, they could support Adrienne Sheck's work at Barrow.
22:26
It's It's difficult to get funding for these types of studies, uh and I know sort of the the project was stopped and started because because of funding.
22:36
Uh And I don't think it's a lot of money, either.
22:41
So, if you look up Adrienne Sheck's work, and maybe she may have some kind of donation link there.
22:45
Uh I'm not sure she does, but uh but it would be great for people listening to support her work in that clinical trial, cuz there's still a lot riding on that trial.
22:56
The research is being conducted in a way that really fits the the criteria we think is important.
23:05
So, we're being assured that the patients are actually in ketosis and they're monitored and recorded in ways that'll help really get questions answered.
23:19
Uh the clinical trials are in progress right now.
23:21
So, they're they're continuing to recruit more patients.
23:25
Most effective for targeting cancer, this Warburg phenotype, and that would be like 80 to 90% of of cancers will have uh an increase in will demonstrate high intensity on fluorodeoxyglucose PET scan.
23:45
And these are the the cancer cells that are more glycolytic are also the ones that are going to be more invasive and more deadly.
23:54
And they're the ones that uh so are are growing more rapidly.
23:57
So, as they're consuming more glucose, that glucose is shuttled to not only energy, but also the biomass of the tumor.
24:05
So, when you're imaging the cancer cells lighting up, that's really they're shuttling all that glucose to increase the biomass of the tumor.
24:16
Uh and when you look at like a cancer or uh prostate cancer where it's not lighting up, it's growing so slow that it's it's not really it it's glucose demands are not that high.
24:25
So, in many cases, probably just better left alone.
24:31
You know, when when people are diagnosed with having a tumor, they kind of think about it as like this alien that needs to be chopped out of the body and with slash and burn techniques.
24:42
But, there's many autopsies.
24:45
I was reading a number of books and and papers on this.
24:49
There's many autopsies have been done on people that die from completely unrelated causes that are full of tumors that had, you know, that that have tumors and absolutely no problems at all.
25:01
So, they may have lived, you know, many years, if not decades, with with tumors and had no problems at all.
25:08
So, if you're diagnosed and, you know, that that's why um it's just, you know, watching and waiting is an is an important thing.
25:15
So, that's we can live, you know, with cancer many types of of tumors with with no problem. Dr. Fine and Dr.
25:23
Feinman, I believe, did some work in vitro on multiple different cancer types with ketones and showed that uh the the gist of their work was that uh a large majority of cancer cells uh cannot effectively use ketones for energy.
25:47
So, that that goes across multiple different cancer cell lines. And I know Dr.
25:52
Brent Reynolds, he's doing work at University of Florida in Gainesville.
25:58
Bill, he's done work uh preclinical work on colon cancer, breast cancer, and glioblastoma.
26:03
And some of the glioblastoma cells were taken from patients.
26:09
He uses a He uses a patient-derived xenograft model.
26:14
I think most importantly, it's like the evidence points to this being the ketogenic diet is doing no harm, right? Do no harm therapy.
26:24
So, we know through at least two or three two pilot trials that the ketogenic diet is well tolerated.
26:32
We know from the epilepsy community that the ketogenic diet, you know, very well tolerated.
26:36
I think it was Melanie Schmidt that did work on the title of the paper was the effects of the ketogenic diet on the quality of life of 16 patients with advanced cancer, a pilot trial.
26:52
So, of those that completed the diet for 3 months of treatment, there were patients with ovarian, breast, sarcoma, osteosarcoma, esophageal cancer, pancreatic cancer, uh thyroid, colon, endometrial, lung, and stomach cancers.
27:12
So, a variety of different cancers.
27:15
Um uh there was an improved quality of life, and there was no sort of major adverse effects on various blood parameters.
27:28
And the side effects reported were really minimal.
27:31
So, they were kind of like temporary constipation and fatigue.
27:36
There's a lot of good evidence already that the ketogenic diet can work on a variety of different cancers. Uh we need more studies.
27:43
Some of those studies are in progress.
27:46
So, I'm going to transition now to random questions here.
27:48
Um So, Scott Shear asks, I know Scott. Hey Scott.
27:54
Uh talk talk about ketosis and hyperbaric oxygen therapy. How, why, and when?
28:03
So, um It's a good question, and I think it's going to vary depending upon the individual.
28:10
And I think generally younger patients can tolerate more hyperbaric oxygen and get benefits from it.
28:19
So, with hyperbaric oxygen therapy, you get the immediate benefits from hyperoxygenating the area that you're trying to treat, right?
28:32
Whether that be an ischemic wound, you're trying to reverse tumor hypoxia and saturate the tumor with oxygen to stimulate oxidative stress, right?
28:42
And apoptosis in the in the wound in the um in the cancer, which is much like a wound actually.
28:50
Uh so you have that effect.
28:52
If if someone has a brain tumor, they're going to be more susceptible to CNS oxygen toxicity.
29:00
So you want to start them really lower. Uh like, you know, 1.
29:06
5 atmospheres uh of oxygen uh and do that for, you know, 45 to 60 minutes and then work up from there.
29:15
So the protocol that we used in our preclinical model was 2.
29:18
5 atmospheres of oxygen three times a week.
29:24
And that varies from what you use for wound healing, which is kind of Monday, Wednesday, Friday or no, uh Monday through Friday, five times a week.
29:33
Uh like two atmospheres of oxygen.
29:38
So it really depends on kind of who you're treating, what you're treating.
29:43
And the approved therapies for hyperbaric oxygen, there's like 14 different FDA-approved, and you have air and gas embolism, uh bone infections, uh osteomyelitis, uh burns, carbon monoxide poisoning.
29:58
So you would want to use the maximum concentration of oxygen to get the uh to push that carbon monoxide off of the uh off of the hemoglobin molecule.
30:11
And it's also occupying like uh you know, cytochrome four, the electron transport chain system, causing tissue hypoxia.
30:19
So you want to you want the maximum amount of uh of oxygen for that or tolerable.
30:26
Certain types of brain or sinus infections, uh decompression sickness.
30:31
So this is sort of gas gangrene is another that's an anaerobic bacteria.
30:35
So hyperoxygenating it can help to kill it.
30:41
Uh necrotizing soft tissue infections, radiation injury, for example, damage from radiation therapy for cancer can be effectively treated with hyperbaric oxygen therapy, skin grafts, and wounds that have not healed with other treatments.
30:58
For example, treating like a foot ulcer for someone with diabetes or very bad circulation.
31:05
The wound healing process is enhanced by increasing tissue perfusion and or increasing the oxygen content, you know, within the actual tissue, lowering reactive oxygen species, so which is kind of a secondary effect and lowering inflammation.
31:28
So, when it comes to cancer, so that would be an off-label use, a non-FDA approved use of hyperbaric oxygen if you're not getting radiation therapy.
31:39
And I would ask you just to look at some of the research that my colleague, research associate Dr.
31:47
Angela Poff, was first author on a number of manuscripts.
31:50
If you just Google ketogenic diet and hyperbaric oxygen, so we have a number of manuscripts that are open access and that are downloadable that describes the use of this approach, the combination of nutritional ketosis with a diet or supplemented ketogenic diet with hyperbaric oxygen.
32:10
We think that this combination is not only effective, but nutritional ketosis will enhance the safety and the efficacy of hyperbaric oxygen by preventing the potential of CNS oxygen toxicity seizures.
32:29
It's a limitation of a of a Navy SEAL diver is CNS oxygen toxicity.
32:34
The limitation of the therapeutic potential of hyperbaric oxygen therapy is the the limitation of the dose to avoid CNS oxygen toxicity.
32:51
So, we can more safely use a higher dose of hyperbaric oxygen therapy and sort of blast a tumor with high levels of oxygen and oxidative stress.
33:01
We could do that more safely in the context of getting the patient into nutritional ketosis.
33:09
And we think that nutritional ketosis will the antioxidant defenses of the highly glycolytic tumor cells that rely pretty heavily on the pentose phosphate pathway or shunt to generate the reduced intermediates and to to actually generate the glutathione reduced glutathione in the cell.
33:33
So, that sort of process is limited or crippled uh when a patient is achieving that metabolic zone and so the hyperbaric oxygen therapy would work much more effectively.
33:47
Next question, Justin Bowman.
33:51
How long would an amateur endurance athlete need to be in ketosis to get the full benefit of being fat adapted for a marathon?
33:59
And what would you recommend as a supplement stack to fuel a marathon?
34:04
For example, MCT powder combined with map essential amino acids, sodium, and some form of electrolyte every hour.
34:14
So, {question mark} uh Good question and it's one that I get often, so I included it in here.
34:19
Ben Greenfield has spoken pretty extensively on intra-race supplementation.
34:24
But, any ketone supplement that you use during a race, you want to make sure that you've tested that pretty thoroughly before you actually use it.
34:32
You know, you've tested it through your training extensively and titrated it up to the point where you start to get GI stress.
34:45
So, you want to make sure that you know what kind of doses you can tolerate before you start using it intro race or intra race supplementation.
34:55
We've done some experiments in the lab and I've done experiments on myself and the pure caprylic triglyceride or the C8 may be the best alternative to medium-chain triglycerides, which is a combination of the C8 and C10.
35:16
So, the longer So, that would be That would be helpful supplementation.
35:19
Branched-chain amino acids, I think, are really helpful.
35:24
Um Other than that, I think, you know, it's your preparation is really what's going to be most important is that you're adapted to burning those fuels.
35:34
And the longer you're on a ketogenic diet or keto adapted, the more benefits you're going to derive from it and the easier it gets, too.
35:41
So, this may take months or even years to get fully optimized to the ketogenic diet.
35:50
So, when you switch fuel sources, your body your body's physiology doesn't automatically, you know, switch over.
36:00
So, there's a lot of complicated things happening from an upregulation of the transporters, various enzyme systems, liver metabolism, uh gene expression, uh for these to be fully manifested, it's going to take some time.
36:16
It's going to take a significant amount of time to be fully fully optimal.
36:21
And from the the really advanced athletes that have communicated with me, they said it took about a half a year for them to sort of get their stride on a ketogenic diet.
36:33
So, I would say just keep that in mind.
36:35
Johnny uh Valamer asks, uh this is a question I get often.
36:40
Should an APOE4 carrier be careful with a ketogenic diet? It's a great question.
36:48
Um so, interestingly, the study that was done by Sam Henderson, which looked at the effects of an MCT oil-based product.
36:59
At the time, it was called AC-1202.
37:02
They looked at at um patients with mild cognitive impairment and found that the the patient population that was APOE4 positive did not respond as favorably at least to medium-chain triglyceride supplementation in regards to enhancement of cognitive performance.
37:28
And they had a a mild, very modest boost in beta-hydroxybutyrate.
37:33
I I would direct your listeners, Tim, to the IHMC Stem Talk.
37:36
It was episode 12 with uh Dr.
37:41
Dale Bredesen and discusses this topic fairly at length.
37:46
Um and you know, covers a lot of things that that I was interested in as far as what signaling effects uh APOE4 sort of is manifested in the brain and how we can target that, you know, actionable things that we can do as individuals to mitigate some of the uh effects of being APOE4 positive.
38:10
And we know that the APOE4 seems to play uh seems to influence NF-κB signaling.
38:21
So, the issue that APOE4 enhances the pro-inflammatory effects of NF-κB and tends to reduce the the activation of SIRT1.
38:33
So, if we think about what the what the ketogenic diet does, and you can apply this to calorie restriction and intermittent fasting, to the metabolic and signaling effects of nutritional ketosis would be favorable to those with APOE4.
38:53
I think I would emphasize the that not just an MCT-based supplement, which was done the Henderson uh study using AC-1202, uh which was published years back, but actual carbohydrate restriction associated with nutritional ketosis.
39:12
Um you know, inflammation is really the driver here from from how I understand it.
39:20
You know, nutritional ketosis, intermittent fasting, uh all these things activate pathways that are downregulated by having this uh uh beneficial pathways that are downregulated by having this genotype, and it also doesn't silence, but it attenuates a lot of the pro-inflammatory pathways that are associated with uh with being APOE4 positive.
39:50
So, you know, having this APOE4 gene, these these carriers would have a survival advantage in in several different, you know, situations.
40:00
So, the negative effects of being an APOE4 carrier really happen later in life.
40:07
So, as we age, it'll be more important to follow nutritional ketosis and perhaps an intermittent fasting protocol. Uh you know, exercise.
40:20
We know exercise increases BDNF.
40:22
Uh intermittent fasting, intermittent dietary restriction.
40:25
So, even if you're not fasting, you know, do calorie restriction. Strength training.
40:34
So, strength training is going to build the lean body mass that functions in glucose disposal.
40:38
So, other supplements that may help individuals that are APOE4 would be berberine and maybe metformin, too.
40:48
I think we need to study that.
40:48
I don't know if there's any It seemed like an obvious thing to do, kind of a study on those that are APOE4 positive and the effects of of metformin.
40:58
So, I know there's quite a few individuals out there.
41:01
I'll look on clinicaltrials.
41:04
gov to see if that's Uh Matthew Maverick has a question regarding cheat meals.
41:12
Any downside to kicking out of ketosis for an occasional cheat meal, or does one need long-term sustained ketosis to get the benefits?
41:25
Uh I found that I can get back relatively fast, especially if I run the next day. That's what he said.
41:30
So, So, there's no downside unless you are using it to manage a disease process, right?
41:39
So, Andrew Scarborough talked about having uh brain tumor.
41:41
I listened to his podcast yesterday.
41:43
So, I would definitely recommend your readers look up uh the podcast.
41:48
I think it's on Quantified Quantified Body by Andrew Scarborough, who has like a grade three brain tumor and he's using the ketogenic diet um and an interesting sort of list of supplements and foods to manage his brain tumor uh above and beyond what he said was was even possible.
42:11
And he happens to have seizures, too.
42:12
So, the seizure would be an indication that he's not following, you know, is kind of getting out of that metabolic zone that is sort of optimal for the management of the cancer.
42:24
for the management of the cancer. So, he's called it like a blessing that the that the epilepsy was sort of helped him with cancer management, cuz when he got a seizure, he it sort of was an indication or an aura before having a seizure, sort of like a pre-seizure
42:42
event, and that he had a protocol that he could quickly administer things like magnesium chloride and or or, you know, exogenous ketones to quickly get him back into a state of ketosis to uh I don't know if you're an athlete or kind of managing some kind of pathology, but occasional cheat meal for performance, I think it's totally fine. Uh
43:06
Uh the the problem that I run into, if I do a cheat meal, uh like I just call it like a refeed, and I like eating a huge junk diet, so I tend not to cheat that much.
43:16
Uh what I'll do is sometimes just eat more of the same foods.
43:22
Uh but occasionally, I'll go out for sushi and have rice and and some other things.
43:26
And what I notice when I do that is that I get hungry at night.
43:30
So, I will wake up instead of waking up my normal time, I'll wake up a few an hour or two or three earlier and just be really hungry.
43:40
Because the carbs that I ate the night before, if I cheat, it's usually in the evening, uh get what is likely a a an insulin dump that makes me hypoglycemic in the middle of the night, and you know, if I don't have the ketones there, if the the insulin shuts off my own ketone production, that my body senses that hypoglycemia, and I feel uh I I wake up with the shakes, I feel get that hypoglycemic effect at night and that that happens.
44:12
You know, that that's what I notice.
44:12
Um, so my suggestion would be if you're going to do a cheat meal and you want to if you're doing nutritional ketosis, uh, do a slow carb approach and and add sufficient amounts of fats and I think you'll get a better response.
44:28
I don't know why, you know, if you do a cheat meal, I guess you're just trying to restore your glycogen levels or kind of reset your system.
44:36
I think you'll get a better restoration of liver and muscle glycogen and you'll get probably a better hormonal response in terms of restoring some of the hormones that you think may be suppressed.
44:51
So, T4 to T3 conversions or that sort of thing.
44:54
If you sort of balance the meal out and just don't go crazy eating, you know, keep in mind that a cheat meal can do an incredible amount of {quote} {unquote} damage in regards to fat gain.
45:07
So, it should be a calculated sort of meal and you should have cap it off and do some, you know, you might not need to bring a scale with you, but just figure out, you know, how many calories you're going to eat.
45:20
I'm not going to go over like 400 g of carbs or something like that because I've seen people eat 1,000 g of carbs in one sitting and that's no lie.
45:28
So, uh, so if you tend to go out of control, uh, and you eat a big bowl of and just you know, eat a huge bowl of fries or just go out of control with chocolate cake or something like that.
45:39
One strategy that I've done is, um, if I'm going to go out and have sushi, for example, or have some kind of meal that's carbohydrates, I'll have a big bowl of soup before and that will sort of send the signal to my brain, your your brain's pretty good at sensing the amount of volume and weight of food that's in your stomach.
46:04
So, if you send that signal uh to your brain before you actually start eating the food, that'll kind of cap off the amount of uh calories that you can you'll comfortably be able to eat.
46:19
Uh so, the next question comes from Blue Light Diet.
46:22
So, I assume it's the author of this book or website or whatever.
46:24
So, and in caps, he says, "Explain this, Dominic D'Agostino."
46:32
"Ketogenic diets have no metabolic advantage uh as shown from the Nusi study."
46:37
So, I I've gotten a lot of emails about this, and you know, I don't know.
46:41
I know Nusi is doing a lot of really great funding a lot of great research, and I know one of the studies may have surfaced at least in a in abstract form at a conference in the form of a poster.
46:58
Uh So, from my understanding, there's really nothing to explain.
47:01
Uh if calories are completely you know, isocaloric between the diets, sure, that makes sense to me at least that there's not going to be sort of a metabolic advantage.
47:16
You know, when I think of the ketogenic diet, and when one sustains nutritional ketosis for some time, it's actually enhancing metabolic efficiency.
47:25
There's some theories out there that if you follow ketogenic diet, it'll increase uh brown fat accumulation, which could you know, allow one to burn off more calories.
47:36
If you want to lose weight on a ketogenic diet, you simply have to calorie restrict.
47:40
Uh that's sort of thermodynamics, right?
47:45
Uh just like a standard diet.
47:48
So, the advantage of, and I hope this comes out of the the research, and I'm sure it will.
47:52
The advantage from my perspective of a ketogenic diet is that your appetite is suppressed, so you naturally eat less.
48:03
So, if you're you don't have these big postprandial blood glucose excursions and trigger a hypoglycemic response, you're not it's not going to trigger cravings.
48:16
So, I've seen it in myself and I think that's the main advantage of the diet, you know.
48:20
Um if you want to hear like a counterargument to um what was sort of presented as no metabolic advantage from the ketogenic diet, if you want to hear a counterargument to this uh there's a 10-minute YouTube video that you can read from Dr. David Lud- Ludwig or Dr.
48:42
uh Fineman's response to that.
48:44
So, there's more data to emerge, but we need to um we'll leave it you know, at that for now and until more of the studies start to surface. So, Hamilton R.
48:59
Blair writes, "Dom, in a podcast with Rhonda Patrick, you alluded to the fact that dairy doesn't do well for you and that you have a mild allergy to nuts.
49:08
Uh what is your primary sources of fat for a modified ketogenic diet?
49:15
Uh MCTs, coconut cream, um milk, oil, butter.
49:19
So, my primary fat sources are uh eggs.
49:25
And I'm kind of picky about the eggs that I get.
49:27
I try to source out, you know, um local eggs kind of from free-range chickens, uh avocados, olive oil, yes, MCT oil.
49:37
Probably about a third of my calories come from fat calories come from MCT oil or coconut oil with combination of the two.
49:51
Fatty meats and fatty fish for sure.
49:53
And uh I do I don't do well with a lot of nuts, but I do okay with like maybe a half cup of macadamia nuts per day.
50:02
And that's a pretty big amount of fat.
50:05
So, yeah, I can't think of any other kind of fat sources, but you could pretty much fill the gap in calories with egg yolks and avocados and MCT, and especially if you're sourcing out fatty meats or poultry with uh with the skin on it.
50:24
So, Damian Matthews writes, "I listened, but don't remember if you discussed Metformin uh or methylene blue or other non-food substances he's exploring for longevity." Oh, methylene blue.
50:36
Yeah, I know a little bit about that, but I know a little bit more about Metformin.
50:42
So, there's a couple interesting studies sort of ongoing being set up now.
50:47
Actually, the MILES study, which stands for Metformin in longevity study, is a pilot study to examine the effect of Metformin treatment on sort of the biology of aging in humans.
50:59
It's really looking at the uh how Metformin can restore the gene expression profile of older adults uh with impaired So, older adults that tend to be impaired in glucose tolerance to that of young healthy subjects.
51:16
So, how does Metformin alter that gene expression profile?
51:23
Really interesting questions.
51:23
We don't have answers yet.
51:24
I know there's uh University of Alabama is doing a multi-year uh trial on Metformin and longevity.
51:34
Um I think there's a you know, maybe a couple other studies that are being developed now that you might be able able to find on clinicaltrials. gov.
51:44
So, it does It that Metformin has a calorie restriction mimetic effect in regards to signaling.
51:51
So, it lowers blood glucose.
51:56
It suppresses it lowers insulin a little bit.
51:59
It wait it lowers glucose in those that have high blood glucose and in those that don't have elevated blood glucose, it lowers it but not that much. Very low.
52:13
Uh it does I found myself and then others and I think in animal models is showing this too.
52:19
There's an elevation of ketones.
52:24
Uh and I think that elevation in ketones is further enhanced if you're on a ketogenic diet suggesting that it may be enhancing fatty acid oxidation in the liver.
52:36
Metformin is pretty powerful activator of amp kinase and it may lower mTOR signaling, you know, etc. etc.
52:44
So, it does all these things are things that calorie restriction do and we think that the benefits of calorie restriction are likely mediated by some of the things that I mentioned and undoubtedly there's many other things that that are also happening.
53:01
There was a study done in rats and it's important to you know, acknowledge the type of strain because there's strain differences when we we realize this when we work with different animals.
53:15
These were Fisher 344 rats and uh there's study showing Metformin supplementation on the lifespan of this rat model and no significant lifespan extension was observed with Metformin supplementation uh at least at the dose that they used in the study and I have to go back and look at the study.
53:38
Uh when we give Metformin, a lot of some of the studies just kind of inject metformin as like a metformin hydrochloride solution.
53:46
We actually I think it's important to mix it in with the food and that's what we do with our studies.
53:51
So, when um you know, the standardized the standardized dose obviously from a scientist standpoint it makes sense to just kind of go in there with a syringe and give x amount of metformin, you know, intraperitoneally or subcu to all the animals.
54:10
So, you know exactly how much you're doing, but the the rodents pretty much eat the same amount of food give or take a few grams every day.
54:17
So, we actually mix the metformin into the food.
54:20
So, when the animals eat the food uh they will get the metformin we think when they need it, right?
54:29
So, the metformin helps to kind of normalize blood glucose in response to a meal.
54:32
And I think other investigators may do kind of injection of the metformin or they put it into the water, but we think it's it's important to sort of give the metformin while you're giving calories that would increase blood glucose or insulin.
54:48
So, it helps to to mitigate that that effect.
54:53
Uh so, in this rodent study they saw no extension of of lifespan with metformin.
55:01
Uh my concern with metformin is that the side effects for long-term use.
55:07
So, I've used it sort of in myself and uh I kind of like the effects of it.
55:11
I think it it generally has like a little bit of a calming effect over above 2 g starts to give some GI discomfort.
55:21
Uh one of the side effects that I've observed with metformin is that it caused I guess you would call it a photo reaction or photodermatitis on my wrist.
55:33
And you know, why is it doing that?
55:37
It's It's something I don't know.
55:39
I've kind of looked into.
55:41
And so, my wrists are kind of the dermis of both of my wrists are kind of messed up because I use lifting straps.
55:46
And uh and in the past I used to kind of handle a lot of weight with uh doing shrugs.
55:54
Like kind of damaged the underlying dermis.
55:56
And that area kind of would get eczema, which I did when I was following a high-carb diet.
56:02
It would occur in those areas.
56:03
So, those areas are just really sensitive areas of my body.
56:05
And when I was on Metformin, and I think it may have accumulated in my system and I went outside, that those areas would be highly uh reactive to to light and it would start to sort of get hives in that area.
56:23
So, I stopped Metformin and then I transitioned to berberine and that completely went away.
56:26
So, uh and Metformin also has the issue that a lot of GI discomfort with Metformin.
56:33
And there's also some data to indicate that it could reduce the uh transport and utilization of B12.
56:41
So, you might want to supplement B12 with that.
56:46
But, when it comes to using Metformin for longevity, um I don't I think the jury's still out.
56:55
And we need to look at that and that's something we actually may do in the lab in our aged animal model.
57:02
But, for longevity, the things that I do, you know, are the big the big things obviously are just strength training, you know, muscle.
57:09
Biggest factor of aging, the biggest consequence, I guess you call it pathological consequence of aging, would be a loss of of skeletal muscle.
57:19
So, the most important thing to do would be intense, you know, heavy weight training a minimum of twice a week to help preserve as much muscle as possible.
57:29
And things that enhance our mitochondrial health and vitality.
57:35
And that would be nutritional ketosis, intermittent fasting.
57:38
I'm not a big fan of endurance exercise, but I do go for walks a couple times a week.
57:47
Um and I need I would need to force myself to do this, but I think high-intensity interval training done two or three times a week would be would be optimal for getting longevity effects.
57:59
So, I just have not been able to get myself motivated to do the high-intensity interval training.
58:06
The next question comes from Josh Brackett.
58:10
Does a ketogenic diet can I use it for glycolytic training? Um Muay Thai.
58:16
Question I get quite often.
58:16
Uh the combination of of diet and training together uh produces an adaptation.
58:28
So, what you're really going for, yes, you can use a ketogenic diet for glycolytic training, but you have to train for that.
58:36
You have to sort of do the training and follow the diet, and over time, and time being like over 3 months, um I'm convinced that your body most people's metabolic physiology will adapt to uh a ketogenic diet, you know, with glycolytic training.
59:00
And you know, if we we talk about maybe losing some of that that quick firing of the type 2 fast-twitch low oxidative fibers, you know, we want to keep that power, that strength.
59:12
You can if you're supplementing with things like creatine, and if you're eating red meat, uh I I think it may be a little more important if you're on a ketogenic diet to supplement with a good creatine product.
59:26
Creatine monohydrate would fine.
59:29
Uh not all people will be able to adapt to the diet.
59:31
So, I think that's kind of important, but I think most importantly it's to give it an honest try.
59:39
You've got to give it about 3 to 6 months.
59:41
And you may just shift to a low carb for a while with some ketone supplementation and before you actually try a ketogenic diet.
59:51
So, so that may be why like short-term ketogenic diet studies on performance show a decrease, right?
59:59
Cuz there's a a lot of the low carb studies out there that are {quote} {unquote} ketogenic.
1:00:06
They just don't have the athletes follow the diet long enough to be sufficiently keto adapted um to to really get the benefits of the diet.
1:00:16
So, yeah, I know Jeff Volek Volek in his FASTER study did athletes that had been adapted to a ketogenic diet for like a year or more.
1:00:24
And if you look at their fat oxidation rates during training, these are endurance and not not glycolytic training, but they're burning, you know, two times, roughly two times more fat.
1:00:39
Uh and that's that's preserving glycogen.
1:00:43
So, in the context of glycolytic training, uh if your body is fat adapted and and the athletes were burning considerably more uh considerably more fat just at rest.
1:00:59
The the practical advantage there is that you're preserving uh muscle glycogen uh for the event. Gerard E.
1:01:06
Dawson the third asks, "What is it like to be an academic who also makes serious weight training big part of your life?
1:01:16
And how do you do two pursuit How do these two pursuits complement or complicate each other. Uh it's a good question.
1:01:25
They complement each other because the lessons that I learned um from training you know, weight training over the years.
1:01:36
The first book I read was Arnold The Education of a Bodybuilder.
1:01:39
I think I was like 13 or 14 years old and um that book probably saved me in some way because at the time I was like a horrible student.
1:01:49
You know, I just kind of did what I needed to do to to get past uh in academia.
1:01:54
And when I was sitting in class, the the only thing I wanted to do is leave class.
1:02:01
You know, I could just do the thing about getting home and just doing, you know, just not being in school.
1:02:06
So, um training really uh serious weight training at the time which I did in in my teen years, it really I guess groomed my my mind and and my body, too, for for being resilient and kind of understanding that it really takes hard work to advance.
1:02:27
Cuz when I started training, I was like making no progress at all.
1:02:32
I mean, it had to be I just hard training coupled with fortified with a a game plan.
1:02:39
So, I became like what I would call an obsessive planner.
1:02:47
I would carry this little book with me and write down specifically what I was going to do.
1:02:51
Uh and I did that I have training journals sitting in my office right now, training journals from when I was 14 years old uh and very detailed, like sets and reps.
1:03:07
And I can look I can go back and look at each of those workouts and actually remember it being downstairs in my parents' basement gym and remember it in that um and I sort of parlayed that mindset being very structured and disciplined from weight training.
1:03:26
And it took a couple years, but eventually uh by the time I was 17 or 18, I applied that to my academic pursuits.
1:03:33
And I was more motivated to do so because my the classes that I was taking were a little more challenging, like honors biology classes and things where I was learning about diet, I was learning about a little bit about nutrition.
1:03:51
And so in in academia and for being a scientist, uh the the sort of rigorous uh planning, note-taking, self-evaluation, uh being honest and critical of myself, I think really helps out a lot.
1:04:12
So, you know, if I'm completely honest now, though, I I don't I I would not want to be sort of as as big and strong or into lifting as I was when I was younger.
1:04:24
So, generally, I think serious weight training when it when it comes to bodybuilding, powerlifting, powerlifting at a very elite level, uh is kind of an unhealthy sport.
1:04:38
So, um so, my focus primarily as I've been getting older is longevity.
1:04:45
And your priorities change when you get older.
1:04:47
So, it's not to be as as big and strong as humanly possible, cuz that involves pretty much non-stop eating in my case, cuz I have kind of an ectomorphic body.
1:04:58
So, you're asking, so how do the two pursuits complement one another or complicate one another? Complicate.
1:05:04
So, yeah, so the pursuit of size and strength really contradicts what we want to go after for longevity. Right?
1:05:14
For longevity, we want to pretty much eat the minimal amount of calories that we need to sustain, whereas surplus calories can lead to you know, the the activation of certain pathways and genes and IGF-1 that could contribute to aging or uh an accelerated path to age-related chronic disease and and maybe even cancer. Right?
1:05:43
So, there's that balance.
1:05:43
So, I want to maintain a lot of the strength that I've been able to accrue from my earlier years, but be able to do it in a way and maintain that that that size and strength without compromising my health.
1:05:57
And that's uh And right now, I'm just kind of in the a maintenance phase.
1:06:04
I And I but I still make training uh a priority regardless.
1:06:08
Uh no matter how busy things get in the lab, at work, with teaching or travel or whatever, you know, I I make it a priority.
1:06:17
And I think it's an important to be a lot more flexible in the way that you get uh you get your workouts in. So, be creative.
1:06:29
Uh my time is much more limited.
1:06:29
So, um you know, be able to do a workout on the fly.
1:06:35
I remember we were doing a actually on our way to to Asia, my my wife and I.
1:06:40
Things are before you travel, you're just kind of bogged down with trying to get everything done two or three days out.
1:06:45
And I hadn't worked out for like three days like at all.
1:06:46
I was completely sort of immobile behind my desk and uh we were on the plane and it was like a 14 No, I think a 17-hour flight.
1:07:00
And uh and I had to get up and and walk around and and she got up, too.
1:07:03
And we basically I started doing squats with her on my back in the middle of the aisle.
1:07:08
These are things that that I do now.
1:07:12
I will do like push-ups with her on my back.
1:07:14
Like if I don't have access to a gym, I will go find a tree.
1:07:17
You know, if you're really motivated and it's part of who you are and what you do, there's no excuse that you can't fit in a workout.
1:07:27
Daniel Barachena uh asks, "Okay, your thoughts on John Kiefer's carb night or carb back-loading?"
1:07:38
So, yeah, this is so carb back-loading is actually really effective for gaining size and strength and I did that probably a lot in the early 2000s.
1:07:46
Uh it was something that I was already doing yeah, years ago.
1:07:52
It's important now I understand and appreciate the importance of titrating the levels of carbohydrate to the individuals.
1:07:59
And it's not I don't it it shouldn't be an an all you can eat sort of free-for-all after your uh after your workout.
1:08:10
I don't care how intense your workout is.
1:08:11
Uh that's not going to be optimal.
1:08:14
It's not going to be productive.
1:08:17
So, you want to prevent your postprandial glucose levels from getting too high. Right?
1:08:21
So, you want to to optimize your recovery, to optimize glycogen restoration, you want to uh prevent your glucose levels from getting above, say, for me, it's about 130 to 120 to 130.
1:08:42
And I find that I can if I do carb back-loading, which I I took a little bit of time out and and tried it uh a year or two ago and I was getting a lot of questions on this.
1:08:54
Uh I could gradually sort of amp ramp up my carbs to about 350 uh after a hard workout.
1:09:01
And that's my glucose would start to climb to about, you know, about 140, but I wanted to keep it below that.
1:09:08
And also the types of carbohydrates I consume were pretty important too.
1:09:14
But I think no more, even a large individual, that was way too much.
1:09:19
I think I could get the same effects by 100 to 200 g of carbs for for carb backloading.
1:09:24
It's really important if you're going to do this on a on a daily basis or or weekly or whatever, it's important to acknowledge sort of all the negative things that can result from hitting your body with a massive glucose load.
1:09:41
And doing that immediately after you've done a lot of damage to the body where you've sort of stimulated the muscle in a way where you have a lot of breakdown, a lot of inflammation.
1:09:53
If you throw a lot of glucose at it, it's going to the consequences are not going to be good.
1:10:01
And we know that when your glucose level gets above 140 mg per deciliter that can cause irreversible beta cell loss.
1:10:12
So your beta cells are the cells that produce insulin.
1:10:14
So if you routinely get your glucose levels above that, uh you essentially have beta cell burnout over time.
1:10:24
So that's been shown, that's published.
1:10:26
There's a couple articles, you know, you can find on that.
1:10:30
You can get potentially, you know, nerve damage with it with that sort of high glucose levels and especially in in people that are a little more older and insulin resistance the cancer rates increase if glucose spikes above say 160 mg per deciliter over time.
1:10:51
So if you're getting kind of 160 ml uh milligrams per deciliter um spikes in your glucose by doing these big refeeds, uh it's you could potentially increase your rates of cancer.
1:11:06
Uh stroke risk is increased by about 25% for every 1 millimolar rise in post-meal blood sugars.
1:11:17
So, that has been documented. So, that's important.
1:11:19
So, that's uh 18 milligrams per deciliter uh for every sort of rise.
1:11:26
Um So, you need to consider these things, uh the health consequences to these big boluses of sugar.
1:11:34
So, I've used this approach and I think it produces good results.
1:11:39
Uh like I said, for me, kind of uh I'm over 100 kg and I didn't find that I need any more than 100 to 200 g of carbohydrates post-workout.
1:11:48
And any more than that, and tend what happens is that you just tend to spill over, and you just kind of hold a lot of water after.
1:11:58
You're not effectively storing the glucose as glycogen.
1:12:00
It just gets into your your It just spills over.
1:12:03
So, a slow carb approach uh to backloading is probably um the best approach.
1:12:13
So, if you do this, slowly, you know, add the carbohydrates in and do low gly- lower glycemic carbohydrates to do that.
1:12:24
Um The last question I'd like to address is that about the safety of the ketone salt products on the market, specifically the DL beta-hydroxybutyrate salts that are a part of the Ketogenics uh product, Pruvit KetoOS, KetoSports KetoCana, Forever Green, uh sells Ketopia.
1:12:46
These are all products that I've used and I I like.
1:12:50
And there was a podcast, uh Dave Asprey and Ben Greenfield uh had um Dr.
1:12:58
Beach on and he talked about the potential dangers of the DL beta-hydroxybutyrate salts and and even about acetoacetate.
1:13:10
So, our number one concern when we do research is safety.
1:13:13
So, the FDA really decides kind of what's safe uh as it moves to market and not us.
1:13:23
Uh we screen all forms of exogenous ketones in our lab including, you know, the D beta-hydroxybutyrate, the racemic compounds and acetoacetate esters.
1:13:31
So, it happened to be Dr.
1:13:35
Bruning Grabber's uh ester uh developed at Case Western uh that we used for our CNS oxygen toxicity seizure studies because beta-hydroxybutyrate esters are the D enantiomer of beta-hydroxybutyrate did not work, whereas the Bruning Grabber ester elevated both beta-hydroxybutyrate and acetoacetate. So, Dr.
1:13:59
Beach's opinion is that the DL beta-hydroxybutyrate uh because it's racemic it has a lot of problems potential problems regarding safety uh that specifically that racemic compounds are the lot of inherent dangers in using them.
1:14:20
Uh it's important to note that many drugs are on the market are racemic and that would include things like uh Adderall uh ephedrine uh ephedrine hydrochloride and pseudoephedrine, ibuprofen uh is racemic and these things are proven safe.
1:14:38
And beta-hydroxybutyrate actually has a naturally occurring isomerase uh for the interconversion from the L to the D form.
1:14:48
And there's a mountain of studies, you know, that clearly show that DL-beta-hydroxybutyrate suppresses seizures, inhibits cancer, suppresses reactive oxygen species, um oxidative stress, protects the liver, promotes wound healing, uh reduces inflammation, protects against hypoglycemia and stroke, uh is protective against lipidystrophy, uh a number of rare disorders.
1:15:15
So, I'm just kind of looking through all the publications I have in my file here.
1:15:19
Uh and these effects would would not be observed if DL-beta-hydroxybutyrate was dangerous or ineffective, uh which was, you know, proposed and discussed on the podcast.
1:15:36
And you also need to consider that approximately 10 million doses of DL-beta-hydroxybutyrate salts have been consumed worldwide.
1:15:43
From the Pruvit product to the ForeverGreen to KetoCana, uh sells quite well, and, you know, at least 10 million uh doses, I believe, have been sold.
1:15:57
And there's, you know, little, if any, I don't think any adverse medical um side effects have been reported with this.
1:16:06
Uh just besides diarrhea and kind of loose stools if the dosing gets too high.
1:16:12
And I know some individuals that are dosing really high.
1:16:16
Um if the DL-beta-hydroxybutyrate was toxic, it would have been reported, you know, by all these people using it, and also it would be reported in the medical literature for uh the use of, you know, to treat a variety of different medical uh conditions.
1:16:35
And keep in mind that they're using the pure sodium beta-hydroxybutyrate, which um you know, there's a lot of discussion about sodium being dangerous and we don't think that's the case if it's kept uh at a particular level and not you know, anything is toxic if it gets too high.
1:16:55
But it's also pretty important to balance out beta-hydroxybutyrate and to spread it across various minerals.
1:17:00
So to have a beta-hydroxybutyrate salt product that has potassium, calcium, magnesium and sodium together would be ideal.
1:17:12
I've really gotten hundreds of emails from from people that have given me tremendous feedback on uh the ketone salts and feedback on performance and feedback for the therapeutic uh use of ketone salts.
1:17:27
I don't advise using ketone salts for therapeutic purposes because clinical trials need to be done.
1:17:34
But that does not stop people from using them and and parents, you know, reporting back that their their child is now able to achieve nutritional ketosis and getting many benefits from it.
1:17:46
So I think taking up a lot of time here and we've covered a lot of ground, probably more ground than we needed to um And if you have any I've enjoyed kind of looking through all these questions.
1:17:58
I haven't looked through all of them yet, but I looked through about 80% of them, I think.
1:18:05
They're excellent questions.
1:18:05
Um thank you for listening and uh I look forward to maybe being on again and handling more.
1:18:16
Hey guys, this is Tim again.
1:18:16
Just a few more things before you take off.
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