107. Nitric Oxide, LDL and the Missing Link in Heart Disease | Peter Anderson

Why can two people with similar LDL levels experience radically different cardiovascular outcomes?  In this episode, I speak with Peter Anderson about the possibility that endothelial nitric oxide may be one of the major variables separating these outcomes.

We explore whether nitric oxide can be understood as a protective “bank” that is progressively depleted by ageing, hypertension, smoking, insulin resistance, obesity, sleep deprivation, psychological stress and circadian disruption.

We also discuss dietary nitrate, rocket and beetroot, oral bacteria, sunlight, ultraviolet A, infrared light, movement, erectile function, flow-mediated dilation, ketosis, statins, calcium scores and the emerging controversy surrounding coronary CT analysis in lean-mass hyper-responders.

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TIMESTAMPS

04:38 Why similar cholesterol levels produce different outcomes
06:16 Nitric oxide, eNOS and the endothelial “bank”
09:00 How lipoproteins become retained in the arterial wall
13:50 LDL as a midstream rather than sole upstream factor
16:11 Lipid-lowering therapy and the “sledgehammer” problem
19:17 Atherosclerosis as a redox and endothelial disease
20:59 Flow-mediated dilation and real-time vascular assessment
26:20 Erectile dysfunction as an early vascular warning sign
28:19 Why standard lipid profiles can miss cardiovascular disease
31:19 Dietary nitrate and the DASH diet
33:36 Nitrate-rich food as vascular medicine
37:00 Citrulline, ageing and reduced eNOS function
40:25 Oral bacteria, mouthwash and blood pressure
41:40 Sunlight, skin nitrate stores and nitric oxide
43:48 Circadian regulation of eNOS
46:26 Shift work, melatonin and endothelial repair
50:22 Ketosis, beta-hydroxybutyrate and eNOS coupling
52:36 Traditional populations, movement and vascular health
57:53 Exercise, soft plaque and sudden cardiac events
01:03:42 When might statin therapy be appropriate?
01:11:27 The keto-CTA and lean-mass hyper-responder controversy
01:17:34 Studying people who regress plaque despite high LDL
01:21:37 Lipoprotein(a) and eNOS uncoupling
01:27:14 Infrared light, fourth-phase water and blood flow
01:33:52 Peter’s practical vascular-health framework

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DISCLAIMER: The content in this podcast is purely for informational purposes and is not a substitute for professional medical advice, diagnosis, or treatment. Do not disregard professional medical advice or delay in seeking it because of something you have heard on this podcast or YouTube channel. Do not make medication changes without first consulting your treating clinician.

#NitricOxide #EndothelialHealth #Atherosclerosis #HeartDisease #CardiovascularHealth #LDLCholesterol #ApoB #EndothelialDysfunction #eNOS #Glycocalyx #LipoproteinRetention #CoronaryArteryDisease #VascularHealth #FlowMediatedDilation #DietaryNitrates #Beetroot #Rocket #Arugula #SunlightHealth #CircadianRhythm #ErectileDysfunction #BloodPressure #PlaqueStabilisation #CalciumScore #Statins #MetabolicHealth #InsulinResistance #OxidativeStress #KetoDiet #LeanMassHyperResponder #RegenerativeHealth #DrMaxGulhane #PeterAnderson

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Transcript

SPEAKER_01 0:41

If one could maintain useful nitric oxide for their whole life, I don't believe any of the um uh lipoprotein chemistry in the endothelium could be initiated.

SPEAKER_00 1:00

Tonight I'm speaking with Peter Anderson. Now, Peter is a citizen scientist, he's a published researcher, uh, atherosclerosis uh interest and with a particular focus on nitric oxide. And in this interview, and the reason why I found Peter and his work on in the depths of formerly Twitter now X was his very uh impartial and I would say to the point and logical positions on uh endothyl nitric oxide as it relates to to heart disease and atherosclerotic heart disease. So uh Peter, like please explain or put put forward your position about why you think this could be such an important piece of the heart disease puzzle.

SPEAKER_01 1:51

Well, um there's a lot of uh also division X uh uh in the different hypothesis uh uh behind uh plaque formation. And there's an underlying that there's a lot of great substance. But again, there's a little bit of division, and I feel that I can actually uh bridge the divide. Uh putting it simply, LDL is causal, certainly, but doesn't always have to be. Uh if if we start midstream with lipoprotein retention, it's 100% necessary uh to uh be involved in lipoprotein retention process and from the cascade downhill from there for atheroscolic plaque development. But as far as being causal, it can be causal, but it's only one of seven uh major risk factors upstream that can initiate the process. And starting backwards, I like to look at a uh uh I I believe that uh nitric, starting further backwards, if one can maintain youthful nitric oxide for the whole life, I don't believe any of the um uh lipoprotein chemistry and the endothelium could be initiated. All of it, whether it's very smooth muscle cell proliferation, uh ICAM, VCAM adhesion factors, um uh transgrowth factor, beta platelet drive growth factor, they're all controlled, inhibited by nitric oxide. Sometimes there's a reciprocal relationship. Like I've had nice debates with CAV1. CAV 1's upregulated with hypercastremia, uh uh which regulates nitric oxide, but nitric oxide has a reciprocal relationship with CAV1. And that's where I would actually like to actually just before we was having a just a quick pre-conversation, um having a little bit of a conversation with um a gentleman called David Diamond at the moment now, just on the um uh on the Twitter on the mail, because we're just discussing the order of the glycocalyx. Uh one would naturally think, okay, well, maybe the glycocalyx uh uh damage comes first from the risk factors because there's um uh because then it regulates the sear stress, the enos and so forth. But um I believe that um uh enos uncoupling comes first. And that's what we're just sort of working through right now. And the reason I can explain that is that um if the glycocalyx is damaged, uh thinking in this, think in this direction, it's thought then that it's more permeable, we'll get more entry in the sub-endothelial space uh for retention. But entry into the sub-endethelial space isn't retention. That's just coming in there and sitting there waiting for retention. It doesn't have to be retained. The example I use to actually explain that is that in that great Miami Heart paper, where two out of five are uh middle-aged, long-term exposure, hypercholesteremia cohorts had no plaque of any kind, we can still presume that uh hyperchlestremia uh upregulated CAV-1 and increased transcytosis. So it still went into the sub-endothelial space, but we still need retention. It didn't go anywhere.

SPEAKER_00 5:19

And and let me maybe pause you quickly there to say the question that we're going to be attacking, which you've already previewed so well, is this fascinating observation where there's a subset of people who, despite high LDL, high cholesterol, don't go on to develop atheroscortic plaques in their coronary arteries and therefore heart attacks. And then you also have a subset of patients who, despite never having uh elevated in quotation marks, Apo B total cholesterol LDL, a riddled with plaque and have a coronary artery tree filled with plaque and end up on the operating table in the cardiothoracic surgeon's uh operating theater, you know, getting a triple bypass. So I think that this is the crux of the issue that we're we're kind of explaining. And as you've said, Peter, um what we're we're gonna do that through through nitric oxide and and essentially this could be the differentiating factor. Before we actually go any further, do you mind explaining a couple points and define these the definitions that we're gonna use? Some of my previous listeners will know about nitric oxide because I discussed it with Professor Richard Weller, who is one of the dermatologists who was the first to discover that ultraviolet A light from the sun was able to liberate this this essential gas from skin stores to lower blood pressure. But but maybe define for us how you think about nitric oxide, define what what you're talking about when you talk about the glycocalic and endothelium, the subentomal space, just to really set uh a basic scene so everyone is on the same page.

SPEAKER_01 6:58

Okay, so so nitric oxide is the is a um uh it's an uh it's uh uh ethrogenic uh uh uh athrosclos, ethrosclosus protective agent. I'd like to say that lines the endothelium. Uh now uh certainly uh now mostly uh we were talking about uh endothelium nitric oxide synthase, uh ENOS. There is other forms, uh inos and ENOS, which I just won't go into at the moment. Um I'd like to come back actually to talk about um uh dermal and um uh uh sun-exposed dermal uh generation uh of nitric oxide. I'll come back to that in a second because I found a couple of flaws in a few of the studies uh explain that um it's independent of dietary nitrate. Um but I'll come back to that as such. And so if we can maintain adequate levels endothelial nitric oxide, uh I'm uh all the chemistry, uh, I can't really find any lipoprotein uh retention chemistry. First of all, I like to say that uh I'm on board from the response to retention hypothesis more than the response to injury hypothesis. It can be shown that um uh uh atherosclosis uh can form uh in the intact non-denute endothelium, uh which will bring us back to the uh glycochalics in in a second as well. Um and so um many things deplete. I I like to look at uh in uh ENOS as the bank, and as one of the easiest way to explain it, it's a bank, and and the risk factors are hyperclastremia, uh dyslibidemia, uh smoking, uh, insulin resistance, obesity, uh, etc. etc. hypertension, uh lack of sleep, uh stress, they can deplete the bank. Sometimes uh familiar with hyperclastremia, very high LDL is enough to deplete the bank of endothelial nitric um uh uh of Enos uh to allow the lipoprotein retention chemistry to proceed. Um it's only a recent, I even look at old, uh, even when I was reading a few before, it was coming on today, it's only relatively recently, and the last year or two, uh a great paper in the Athloscosis Journal um articulated a little bit better the initiation point uh of lipoprotein retention, being the protoglycon uh sorry, uh TGF, transgrowth factor beta, and platelet drive growth factor uh increases from endophilial dysfunction elongate protoglycan chains to then allow them to bind to LDL. And they they state very clearly it's uh, I mean it's not 100% binary, but it's but it's the major factor. And so if we don't have this, uh if we don't um have this increase of TGF and PDGF and elongated GAG chains, we can't bind the LDL. It can sit in the uh subendotheral space, whether it's increased transytosis from cave 1 uh hyperclastemia or a damaged, shredded, thinned glycocalyx, permeable, allowing more uh entry, it's still forms of uh transcytosis into the subendothelial space. It's not gonna go anywhere, it's gonna exit again, uh, be processed and so forth, but not retained per se. So the initiation point is also the defining point uh of retention, I think, and I think we'll all agree with that. And then after retention, I'm on board with all the processes from the macrophages, the famous cells onwards. So I think all the good fun is acknowledging the midstream and then coming up and seeing what the factors are upstream. And that's why I I think I bridge the divide a little bit out there that I believe the LDL can be causal. It can by itself lower deplete the bank and allow the initiation of lipoprotein retention chemistry. But sometimes it's not enough. Sometimes when someone's got genetically strong, they've got noting that all the risk factors deplete the bank. If someone's relatively metabolically healthy and young, um, aging alone can deplete by the age of 50 to 60 years old up to 50% of Enos. But if we've got a healthy bank of Enos and high LDL, we still may not have the TGF, PGGF. Uh, and there's a lot more than that. That's just a starting point. Uh very smooth muscle cell proliferation, ICAM adhesion, V CAM adhesion, platelet aggregation, all the lipoprotein chemistry, all inhibited, controlled uh by adequate amounts of uh nitric oxide. So a nice way of wrap of tying that up is that it's a bank. Now, and it's great, and again, I'm I I've uh uh I think it bridges the divine well. It acknowledges that LDL is essential for lipoprotein retention uh and the formation of PARC. It's a hundred percent requirement, but it's mid-stream. Uh it's a part, definitely a part of the process. Um, it can be causal, but other times it can be very low, as we just alluded to, the heterogeneity, but the hypertension, uh hypertension, uh smoking, and the other risk factors can actually uh deplete the bank enough to initiate, even though LDA was very low. And interesting on hypertension, I think it's underrated. I see again on the great division of our wonderful ex, oh no, look, it used to be 160 systolic, and now it's been bought down to make money and so forth down to 120s. But I think a little bit differently is if you go back to the adolescence, the first sign of fatty streaks, coincidentally, it's also the first rise from 90s to the hundreds to the hundreds of tens of systolic blood pressure. If we look at some of these tribes that are noted to have a low incidence uh of atherosclosis, certainly some of them have uh low LDL, but they all have low blood pressure as well. So I actually do think that blood pressure is underrated. But um it all just simply comes back to the bank. We could be lucky. Uh our combination of risk factors, we can genetically hide, genetics are involved as well. It's not just um, I prefer to say the function of enos because you can have overexpression that can uncouple as well. Um, and when enos is uncoupled, in simplicity, uh it's related to BH4 becomes oxidized. Uh, and instead of producing nitric oxide, then it produces uh superoxide, and the superoxide can combine with the remnants of the last remaining nitride to uh nitric oxide to make perioxinitrite, uh, which which is uh which causes all the damage to the endothelium.

SPEAKER_00 14:31

Um questions you want to ask on that on that point? Yeah, so I think what you've said is is really a little very similar to what I'm thinking, which is without a doubt, the these lipoproteins, and that that's what we're talking about here, is LDL is a lipoprotein. Um and it is undoubtedly on the causal pathway for the for atheroscortic cardiovascular disease. But the the point that Pete's making, and I'm I I really this is my opinion too, is that there's there are there are effect modifiers going on here. There are fa other factors at play that are that independently are going to influence uh if someone who does have a higher LDL ends up going to get uh cardiovascular disease. And I really do think that there is this potential order of operations to to look at these different risk factors. And you know, you've described it as midstream. Before we started recording, I was I was using an analogy of a of a you know analyzing a car crash. And I feel like the focus on lipid lowering, like guns blazing, lipid lowering out of the blocks, uh is the equivalent of you know the team rushing in seeing this car crash and you know ascribing causation, but they haven't looked, you know, was the was the road wet and oily before the cars has crashed, you know, was there a driver asleep at the wheel? It's almost like there there wasn't more nuance in terms of understanding what those effect modifying events were. It's just bang, we're gonna you we're gonna, as we said before we started recording, we're just gonna sledge hammer this, you know, this single biomarker into the floor. Now, it doesn't mean that it's not indicated in certain situations. I mean, we're we're probably gonna talk about satin therapy uh you know as part of this discussion. Um there there's a time and a place, but the my my impression or my gut feeling is that the the the prevalence or the focus, I would say, you know, myopia or hyperfixation on one biomarker at the moment is to the detriment of of a greater understanding of what else is going on and therefore what else can be modified. And we we're usually talking about lifestyle practices.

SPEAKER_01 16:53

Yes, and and look, lipid line therapy has a place. Uh so as was just alluding to before, if your patient if I if I was a cardiologist and the patient uh after after taking the case and discussing, realized he's got no inclination, uh, no concern about even working in any of the risk factors, then uh then you might as well go back down to uh actually to limit the damage uh and slow down the rate of PARC growth, stabilize PARC by lowering the lipids. But even having said that, it's a sledgehammer approach. Uh to be fair, uh most transcytose uh LDL exits again. Only 0.1 of all circulating LDL, as I was mentioning before, is actually involved, which seems ridiculous, which is involved in atheroscosis making plaque. Yet we try and load the whole body's circulating 50, 60, 70% now with um P PC SK9 inhibitors on top of a high-level statin. In essence, if it was your back garden and you had weeds, uh then the analogy is you'd be out there spraying it and you'd only be getting to a small percentage of the weeds, and then maybe 80% of those weeds would still live. From what I understand, and and please forgive me out there, X-LAN, but I know it's only over five years, but the latest trials on high-level statins and PCC canine inhibitors um are showing about 25% absolute risk reduction. So that's telling me that maybe up to and only in that five-year period, I understand it can transpose to a lot longer period. But in that five-year period, um 80% of the ones, uh, the match controls who were statistically destined to have an MI or MACE still do. So I understand there's uses for it, and I can see if someone can't get their risk factors and the causative factors under control, it's something that we can work on. But I look forward to the day we can have more efficacious interferences like um uh stopping the TGF and the PD PDRGF um uh elongating, stopping the elongation of the GAG chains and the protoglycans. That would be a good start. Uh and and I think there is a lot of work out there. Um I can name other uh people I interact with on X. Um sorry? I can name other uh people like LiPofan and Josh Wagman, uh, they uh go into the uh uh into areas that I'm less familiar with, a lot of the genetics and a lot of the receptors and so forth. And listening to them talk, I do give me hope that we can get to some of these other more efficacious mechanisms in the future.

SPEAKER_00 19:58

And and maybe even taking a step, again, keeping it higher level. I think the way the way I think about coronary um artery um disease and you know, broadly what's going on with this astraloscorotic process, is that you've essentially you've got a redox problem. You've got a problem of unopposed oxidative stress, you've got a problem of uh essential hypercoagul coagulability and an activation of potentially of this workhouse triad and endothelial dysfunction that's happening in in the arterial circulation. And the the factors that are going to influence the process of um you know glycocalyx damage and and then you know endothelial damage are you know in innumerable, probably you know, at least 30 factors that are contributing to this. And you highlighted some of the important ones. But I I feel like that my my perspective is that we really should be focusing on uh blood vessel dynamics. We should be focusing on how are we optimizing this endothelium blood vessel health? That that should be the primary launching off point intellectually uh rather than you know what is the circulating lipid lipid burden. If it's someone who's had extreme high family history, yeah, of course it's not a uh factor that you're gonna ignore, but should we be jumping onto that as the on the first uh point of call for someone who has a low has a no family history at all and have have had uh you know people relatives live into their their old age with you know cholesterol levels of of six and seven.

SPEAKER_01 21:40

No, no, and and that's right, but maybe in the future we can have a better look. When when I hear early and longer interventions, I'm not thinking of um of treatments per se. I'm thinking of earlier, long uh earlier looking. And so I've been spending quite a lot of time looking at flow media dilation. It's it's the gold standard of uh of atherosclosis preceding endothelial dysfunction. Endothelial dysfunction, I think everyone agrees, uh precedes uh uh atherosclosis. Uh and uh FMD, uh, from what I can ascertain, we're only about five, six, five or six years away from being on smartphones and on watches. Now we can actually see diets that work. Uh not all the science, but some of the science to be settled. Intermittent fasting, there's so much contention uh about, and everyone's pretty earnest and what are they looking at? Intermittent fasting, uh, ketosis, low low carb, um, small particle, large particle. Um Uh high cholesterol is great, no, it's not. Um, it's predictive, no, it's not. Uh, but at the end of the day, if we can look better and we can see that and the beauty about FMD, it can actually ascertain the first change even before the first fatty streaks. Can you explain how it works? Oh, they uh they will hook up basically um uh cuffs in one part of the body with a way of reading the the pressure, and then they'll give you an agent which will um uh cause a vasor dilation uh uh uh andor a constriction and then measure and then measure the differences of it. Um now that we're getting good uh readers, uh we can even read pulses and and so forth, and uh there's nearly even reliable ones in our smartphones, uh the technology is nearly there that it can be portable. When it's portable, now some people will uh transpose that to be predictive. I'm not I'm I'm less worried about that. I'm more worried about the first sign of change. So in the future, earlier and longer to me will actually be an adolescent getting a little alarm on his watch and saying, you better watch those risk factors, you're getting the first signs of change. Um it's it's and and look, it it's it's measured in percentages. Uh when you're about 12 to 13 percent, um you've pretty pretty much got no occlusions, no sign. Uh you've got very very good uh vasodilation, very, very good endothelial function, under about three or four percent. Um it's not really good. Interestingly, they give PDE, and one trial read, they gave PDE5 uh inhibitors, um uh Silus, in other words. Viagra and and uh but Sylas, the longer one, but they gave that it's becoming a bit of a fashion in the atheroscos world, but they actually gave it to uh cohorts who already had established heart disease. And it surprised me they gained five percentage points. They went up to the area that if it was uh if they were primary, uh you would presume that they were that that they had very good endothelial function. So even in secondary, the FMD may at least help to maybe slightly reverse uh help you to refine your treatments, whether it's LLT, whether it's supplements, and your risk factors, to actually get the percentage up. But that's incredible.

SPEAKER_00 25:17

Let me just translate that for the listener. So what what Peter just said is that in in a cohort of people that have established cardiovascular disease, they gave them the medications that are called colloquially known as you know the little blue pill. They gave it, they gave they gave the the Viagra type medication, Cialis, which is Taldalophyll, and what it does, and this relates to the relevance of erectile dysfunction as an early warning sign for cardiovascular disease, when when the blood isn't flowing properly to enable you know solid, solid, literally a solid erection, then that's a that's a warning sign that there's something going wrong. So what Peter's saying is that study showed that if you administer the medication that that essentially um act as a as a aiding in in this nitrate signaling pathway, you vasodilate the all the blood vessels. So that's what how how they enable uh you know a strong erection. But what you you're noticing um is that this marker of blood vessel health, this FMD, improved to the level of someone who potentially hasn't even had uh a heart attack before. Is that is that correct in US?

SPEAKER_01 26:34

Significantly, I mean, we appreciate that uh PB5 inhibitor sciatus, less create nitric oxide, they potentiate it and keep it around longer. Uh that's why they're they're contraindicated with uh drug nitrates, for example, drop the blood pressure dangerously too much, but not necessarily with a little bit of citrulline and um and uh inorganic dietary nitrates, uh no c no contraindication. But um, yeah, that's amazing.

SPEAKER_00 27:01

It's truly amazing. I mean, so true, and and maybe just quickly speak about your perspectives on on this idea of of you know uh erectile dysfunction, because to me that study just is a real case in point about that you're onto something with this with this Enos story, because again, we're linking into the deeper pathophysiology of what's potentially going on here.

SPEAKER_01 27:25

Yeah, well, the the the first sign of a man uh losing his erectile function is normally his nocturnal and uh and mourning erections. Uh, and uh you'll see a lot of people on um uh on in different um uh social media and so forth explaining how when they take citrulline or nitrates they regain those as well. Um again, I would suggest having a little bit of uh uh B tree powder. I prefer arugula powder uh without the without the oxalates, uh, a little bit of citraline so that your uh Silas and Viagra have something to potentiate more.

SPEAKER_03 28:03

Interesting.

SPEAKER_01 28:04

There is a cohort of people that they don't really work well on the PD5 hybrids because their nitric oxide and their endothyl function is so compromised. But again, five percentage points, um each uh each percentage point um um actually uh I've actually actually I've actually put it online, I don't think the exact figures, but just let me note that um per minimal uh reduction of um of LDL uh is predictive, even though it's not so rigorous studies and so forth. And again, I look at it less as a predictive agent, FMD, more than the current changing that's happening and help you refine your risk factors. But uh each percentage uh also tends to align uh for a predictability uh predictive of MACE in the future. And again, they aren't as regular studies, but 5% is phenomenal.

SPEAKER_00 29:00

Um and and and getting back again to this predictive problem, um there was a study done maybe in the mid 20 2014 or something, and it looked at serum lipid levels on it on admission to hospital in patients who presented with cardiovascular disease, whether that was atherosclerosis, whether that was uh you know, worsening angina for stenting, whether I think it possibly could even include patients, you know, coming for coronary artery bypass grafting. And the essentially it was more than half of the patients, and again, this is American unit, so I'm not sure exactly what the exact cutoffs were, but half the patients didn't meet the criteria for hypercholesterolemia um you know, as as they stood when that paper was written. So the the point being is that again, we're we're there's so much emphasis on on lipid lowering, but if half your your patients with symptomatic disease or uh don't have elevated risk factor by your own metrics, then you know, maybe maybe we're looking at the wrong metrics. And that that that's where this FMD comes in is well, if this technology is improving and we can get a real-time minimally invasive look at whether someone's vascular system is really compromised, then it it feels more targeted than what can sometimes feel like tea leaf reading um with some of these lipid profiles. And and and to give people some more perspective and and and get you to comment on it, uh Peter, but you know, I'll do calcium scores on five 60, 60-year-old men, um, you know, all of them with a similar waist circumference and you know, very similar lifestyle risk factors, and you can get extremely wide range of calcium scores, which is evidence of high block. Some of them, you know, I had a guy the other day, I'm like, you know, thinking that this is this is gonna you know he's gonna be in a couple hundreds, you know, it's zero. And then another another person who's looks you're relatively fit cycles, yeah, and he comes back with a you know 400, 500 score. So the the there's there's an abundance of need to understand this disease process better so we can prevent it um better.

SPEAKER_01 31:09

And where is the calcium distributed? You you can have uh in the thousands, no stenosis, uh asymptomatic, and it's more relatively uh uh spread in areas uh uh than concentrate in the LAD, for example. Uh so it's where the spread of uh from from what I've looked at, the CAC. And and we need more work there as well. We we acknowledge that um in uh in kidney disease the role of phosphorus, but it's never really looked at in the dietary side. Um high uh hyperphosphotemia, yes, we look at it there. Uh we look at it uh in kidney disease, but not dietary. And uh and I have read some excellent papers that we should be looking closer at the dietary uh side um uh of phosphorus, the phosphorus to calcium ratio.

SPEAKER_00 32:01

Um before you go on that, can I get you to to back up and talk firstly about dietary uh interventions to manipulate nitrate and then the sunlight-induced nitrate pool? I want you to hit those two topics uh before I before I let you keep going.

SPEAKER_01 32:18

Yeah, well, uh uh uh interestingly, the DASH blood pressure diet, people aren't aware of. There's a lot of variability depending how many vegetables you eat. And it's perceived to be just on the reduction of sodium, uh addition of potassium and and and a few other areas. But when I look at the DASH diet, and I and I've read a few papers on it, you can get um uh 1,1100 milligrams of dietary nitrates a day uh if you just eat a certain pattern. Uh I would I would actually put to you that most people that um just start the DASH diet would would have far more uh um inorganic dietary nitrates than what all the studies show for vasodilation of four to five hundred milligrams per day. So that alone sort of tells us something. So the heavy hitter in the DASH diet, I believe, is the uh nitrate content. Interesting. Now it's a little bit hard. Um a lot of people start off with beetroot, and beetroot does have oxalates, and I'm less concerned about the oxalates for kidney stones, should be. But um oxalates are a great piggybacker of information. Uh uh if you've got a little bit of arthritis and um aches and pains and so forth, I believe oxalates uh uh having enough beetroot powder or juice to get the required 400 uh milligrams per day could be troublesome. Uh myself, I import from overseas um an assayed 10% uh nitrate uh aragule powder. And it's uh I I joke to my local pharmacist friends, it's veritably like uh GPN, natural GTN uh for the uh dilation. And um uh and in men's health circulation, uh blood pressure, um, but it's very low on oxalates and it's got a decent uh amount of vitamin, K and potassium, and I think that aragule is possibly the ultimate uh the ultimate uh nitrate supplement.

SPEAKER_00 34:18

Well, I think let me let me comment in quickly on that again. So when if someone comes into the ED uh, you know, with severe, you know, they're having an NMI and their blood pressure can support it, that we give them GTN, um, which is good you know, glycerol triglycerin trinitrate. So we give nitrates medicinally to vasodilate the arterial system, uh, improve perfusion, uh, and you know, potentially reduce cardiac preload as well. So there's a the this is a well-researched mechanism, and what Peter's proposing here is that the diet to reduce the DASH diet, which is this, I guess, massive, massively researched and you know, substantiated by cardiac organizations and hypertension uh congresses all around the world, has is this idea of how can we uh change our food intake to reduce hypertension? And what Peter's saying is that the commonality there is that it's high in foods that contain nitrate, and that therefore you're giving the patient nitrate and it's providing this pool, you're potentially providing uh uh substrate for these enzymes, um endothelial nitric oxide synthase and others, to work so that they can relax the blood vessels so that the blood flow is better and and your atheroscortic symptoms or your your angina symptoms get reduced.

SPEAKER_01 35:42

And and look, the worst thing about uh GTN and isosorbide is the tolerance. Uh so drug nitrates have severe tolerance. If you tried to say on a on a desert island, uh keep your arteries open, spraying all day GTN, I would suspect it would stop working in a very short time. A lot of people in isosorbide report about 6 p.m. it feels like something's just slammed back shut again and the angina's back, where the um food, inorganic nitrates are longer lasting without the tolerance. But just also stepping back is that we have the two major pathways, apart from the apart from dermal um uh uh and uh and even shear stress uh generated nitric oxiders via enos. But the major pathway in the body is the enos pathway, uh the enzyme. But the problem is, uh, and I like to use the analogy with lactase and lactose. So if you have deficient and uh a lot of things aren't binary, you could be having not that you haven't got any, but you might just have less. If you're deficient on lactase, you might struggle with lactose. Uh diamine oxidase um uh for histamine, for example, you can go to barley and catch an infection and knock out a bit of uh diamine oxidase, another enzyme in the in the bowel, and then uh your minor allergy symptoms or just histamine-containing foods with no history of allergy can actually bring on uh asthma hai fever, itching, weasoning, and seasoning, and worse, angiodema and so forth. And so uh the enos pathway is great, but we I I like the nitrates. If someone's come to me, if they had to choose one, I'd say go the nitrate pathway because the nitrate, dietary nitrates to nitrite to nitric oxide pathway doesn't need the enzyme, it's independent. And so many people don't even know this. It's just um sitting there waiting. I didn't know it myself until I started researching, whoa, there's another way of getting nitric oxide from the diet uh that's independent of the enos. And look, um, if it might even get to the stage, I've come across people that tell me, oh, I'm having 10 grams twice a day or six and well, it might even come to the stage that you're overloaded, that if if you're six, six, it's all right for youngsters. They can have all the arginine situing the gyms. I like doing mine the youngsters. You like to dilate the arteries so you can pump and work harder and push bike and lift more weights. Us oldsters like to stay alive, improve our vision, men's health, our blood pressure, our circulation. But and they have a good uh enzyme. They've got a fully functional enzyme, so they can take um uh ample amounts of citrulline. Citrulline is better than arginine, and by the way, if if you're having citrulline, um, don't have citrulline mallate, it's a third dilution. Four grams of citrulline, uh, four grams of pure citrulline equals six grams of citrulline mallate, uh, apples with apples. But now, so we've say by age alone, we've got reasonable amount of risk factors, uh, and we're 50, 60 years old, we want to get some nitric oxide onto us, we can probably presume by 50, 60 years old that we've lost by aging alone uh of the enos enzyme up to half of it. And then if we've lost half of it, and then we've got um other risk factors, hyperchlastremia, um uh smoking, uh, etc. etc., hypertension, and so forth, all the risk factors um bring down enos function. They all work, they all share the same mechanisms, but in layman's language, they they um they uncouple it and stop it working. Most of oxidizing um BH4, an important cofactor, which stop, which uh then uh stops making the arginine from the sypsiline available without getting too technical and that sort of things. So if you uh uh why don't you have both? Have some sypsiline, but concentrate on the dietary nitrates. If I had to pick either one, I'd recommend the dietary nitrates to get um a good production of nitric oxide. Having said that, uh, and again, because uh you may be, if you've got diabetes, obese, and hypertension, you may only have 10% of the enos function left. And even oversupplying lactose to your deficiency of lactase, it's not that you don't get it, you get symptoms, adverse effects with lactase-lactose analogy. Uh at the least phlegm or allergies and so forth. And so if you have too much with a deficient, uh, at the very least, you won't be getting it. Uh, but there could even be side effects. There is arguments that it can actually further uncoupling. So um I think one should air um uh from sypsiline into the dietary nitrates, and there, and one also then needs to have the correct um uh uh commensual bacteria in the mouth to first change into nitrites. It cycles the mouth before it goes in the stomach and changes to um uh starts changing to nitric oxide with stomach acid. Um you you've read the studies, have you, where they take 24-year-old normo tensive uh youngsters and they use antibacterial mouthwash for two weeks and their systolic blood pressure goes up to 140 to 150.

SPEAKER_00 41:07

Well, uh I haven't heard that, but uh you you you're suggesting that the or the mechanism was that they knocked out these these beneficial commensals that were providing that conversion ability.

SPEAKER_01 41:19

Yes, and and look, and the first step, uh now if you I I try and stay away from uh there is a few manufacturers of supplements for nitric oxide overseas, and they're using sodium nitrite. Um I'm a bit shy of that. Uh uh certainly the nitrites don't need the initial commensual, they'll go straight to the stomach and turn faster into nitric oxide, but I'm just a bit more concerned. Um uh uh more concerned on the healthy side. There's a little bit of evidence of the wrong type of nitrates, not dietary inorganic nitrates, but some nitrates found from farm water coming in uh for cancer, uh creating nitrosomes. Um, I mean, you don't hear of too many people getting uh stomach cancer and so forth from uh the preservatives in meats. But I but if you want to just push a little bit and increase your nitric oxide, I think it's safer to stick into dietary inorganic nitrates. And then when you can get a um uh an araguula powder up to 10%, that now all of a sudden becomes conducive to encapsulating if you don't like the taste of it. Uh, if you tried to encapsulate beetroot, you might have 10 capsules. Uh there is a red spinach uh I've seen overseas. I've I've never actually um personally procured it, but there's a red spinach which is low in oxalate that's also up to 9% uh in nitrates. Interesting. Yeah, but uh but long as you keep that uh crack bacteria. Just want to just quickly just touch on, and this is more your field, that I get lost on the dermal, uh, the sunlight-driven uh dermal nitrates. I I I've I've read papers that saying that it's independent of dietary nitrate, but the papers only abstained from dietary nitrate for two days. It relies on nitrate stores in the body, and I think it would take um probably a few weeks of having no nitrates to deplete that store. So I was quite bemused when I read it, oh, it's independent of dietary nitrate. I thought, this can't be. And I saw in the methods that you always look at, only two days abstention. It was more showing that it's not an immediate um uh lack. But if you had a longer term, and and remember and it um the other interesting paper that I sent to you actually quite shocked me. Uh just for people that are listening now, is that it was actually um um they put nice mice on a nitrate-free diet and they developed severe metabolic syndrome, atheroscosis, myocardial infarctions in a very short time. But I'm thinking, whoa, these weren't knockout enos mice. They still had their normal Enos pathway. How come such a deficiency of diet, a total deficiency of dionitrate, why didn't the Enos, why didn't the shear stress running around kick in and save them? A bit of sunlight generated and so forth. Well, the sunlight would need the uh dietary nitrates, of course, uh if it's total abstinction. But that actually, what did you think of that paper? It quite surprised me.

SPEAKER_00 44:29

Yeah, it I didn't get to read the whole thing in depth, but the the crux of the the matter is that you could generate a, I guess, a phenotype which is consistent with. With this vascular dysfunction uh by by essentially restricting dietary intake. And I mean, there's obviously drawbacks of animal models. We we're there's there's a in some cases a limited applicability. But for the for the interest of everyone listening, if you knock out, if you generate a mouse, mutant mouse that knocks out the enos uh gene, then you're gonna get you get a similar phenotype. So you get vascular dysfunction and and all these atherosclerosis. So so again, that's pointing to the centrality of this Enos, this nitrate story to cardiovascular disease. Um I I I want to tie uh the light back in really quickly and and and weave it into the story because it it turns out that the enzyme, the Enos expression and its activity, unsurprisingly, because uh you know this is how the body works, is regulated on a circadian rhythm. Um, meaning that if you're potentially having circadian rhythm disruption, then you're impairing the correct or the activity, the the daytime or appropriate diurnal rhythm of that ex of that that pathway, and you're gonna get impaired, impaired vessel blood vessel formation, or sorry, blood nitric oxide formation or activity, and then impaired vasodilation and their high high blood pressure and heart disease. And that that kind of ties in a little bit with recent listeners to my podcast were listening to Sean Kane, um circadiologist, and we actually didn't get to speak about his flagship cardiovascular paper, but they were they were noting uh you know the the increased odds of of coronary artery disease up to 32, 38, 40 percent in a cohort who will lighten it is between the brightest and the darkest nights, kind of implying that the more light at night that people are getting the greater degree of circadian rhythm disruption, the more cardiovascular and atheroscopic pathology they're gonna get. And you know, one of the reasons, in addition to you know, all the everything that we're talking about, is probably because they're not allowing proper circadian function of their cardiovascular system, of which you know Enos is is is is a part of this story.

SPEAKER_01 47:08

And and and there there we go. Is that why shift workers um tend to have a high incidence of disease and mortality?

SPEAKER_00 47:16

Well well, it's it's one of the reasons. I mean, melatonin is related, is is promoting vascular endothelial cell progenitor cell health. So uh I the way I think about it, and this is another way of mental model for what's going on with atosclerosis, is that you you've got an imbalance between vessel repair and vessel insult. So if we're if we're incurring all this vessel assault throughout the day, where our blood pressure is higher, we potentially people are smoking, they're fluctuating their blood glucose with uh processed foods and glycemic swings, you know, they've inhaled a bit of lead or diesel particulates, they're shearing, denuding all their glycocalyx, that's fine. But what happens overnight is that the endovascular progenitor cells essentially crawl out of wherever they've come from. I think they've got a myocyte progenitor. Um and then they heal up, heal up under the influence of melatonin, which is secreted in the absence of blue light, they heal up any damage. So, so I think the circadian disruption is an amplifier or force multiplier of any uh daytime vascular insult because it's preventing that endothelium from healing. And therefore, plaque progression over a period of decades could be uh accelerated by or the differentiating factor could have been the fact that person was shift working or was was uh you know on their phone until midnight every night.

SPEAKER_01 48:44

Uh that's all the youngsters on their on on their games to 4 a.m. Absolutely.

SPEAKER_00 48:50

Absolutely. I I I want to take it back though, because what you said about the the dietary sources is so interesting because a lot of people have adopted low carbohydrate or carnivore diet um to address insulin resistance. And they've noticed a real improvement of of say blood pressure, they've lost a bunch of visceral fat around their around their midline, they've probably lost some epicardial and and and pericardial adipose tissue, which we know is also involved in the pathogenesis of cardiovascular disease. But I guess what you're saying, Peter, is that if you're going to include it, you know, you're making a good case for including greens that are really rich in these nitrates. And and it's not as simple as, you know, all the plants, you know, plants are trying to kill you. They might be, but it might be uh valuable for the medicinal benefit of in of these nitrates to uh to have them in your diet.

SPEAKER_01 49:47

No, that's right. And and um so I do appreciate why people go carnival. If you've got um uh Crohn's disease ultra colitis and it resolves the issue, I totally understand that. But if our if we had to just instead of being so binary, just sneak a little bit of something in, I pose a little bit of aragula as conducive, texture, everything to go and those scrambled eggs. A little bit of rocket leaf. And it's low FODMAP, it's low carbi, it's low histamine, it's low oxalate, uh, low salicylate. So for all the reasons that we don't have plant matter, um not I'm I'm not I'm I'm agnostic to keto, not I basically eat a low-carb diet, but I don't try and get into ketosis, but I understand um some of the health benefits for some of the people that do, including carnivore. But if I could give some nice advice after especially reading that um uh study on the low nitrate diet, and just such a great free kick to get a bit more nitric oxide in, um, why not add just a little bit if you if you're gonna pick any plant matter at all, pick a little bit of avolula.

SPEAKER_00 50:57

That's that's great. I I think that's a really good, uh, very nice piece of detective work you've done there, Peter.

SPEAKER_01 51:03

Just so quickly on uh keto, I've just got I've got a little note here as well to remind myself. We had a fascinating paper. I don't know, I'm not that versed in keto as others, but this was a study on a smoking rat model. And they gave it um uh BHB, uh uh which is produced uh equivalent from what's produced by uh ketosis.

SPEAKER_00 51:27

So beta hydroxybutyrate, which is a ketone body that the liver the liver produces.

SPEAKER_01 51:31

And surprisingly, Nil, uh so the these um the these uh rats smoking uh the ROS pit right up. I don't know how they do a smoking model, but they do it. Wonder what brand they give it. But but the interesting thing was uh so when they gave it BHB, it actually reduced the ROS, but more important, I'm sorry, the these these uh these uh smoking rats, ENOS totally a coupled. They measured the ENOS function and went right down. When they introduced BHB, it um got rid of the ROS and recoupled the Enos. But what impressed me is it also um the intermediate thickness actually reduced while they were still smoking. So in other words, hypothetically, these rats on ketosis, they kept smoking and the ketosis, the ketosis, particularly ketone, negated the fix of smoking, got rid of the ROS, and recoupled the Enos while they're still smoking so well that it even uh uh improved the intermediate thickness.

SPEAKER_00 52:44

Wow.

SPEAKER_01 52:45

How crazy is that?

SPEAKER_00 52:47

That that's a remarkable fact. And yeah, we're not suggesting that you can take up smoking if you're just in a on a kid.

SPEAKER_01 52:54

But it comes back to that thinking, isn't it? It comes back to that bank. If we can if we can regain X amount of an ENOS bank, um no, we don't encourage you to know now go and enjoy some of those risk factors and not worry about the hypertension and diabetes because my ENOS is so high. That would be possibly be a fear of the F and D. People might relax too much.

SPEAKER_00 53:18

The I think the crux of what it's illustrating, though, is again how multifaceted this this issue is and how many again effect modifiers are at play here that are probably related to genetics and and genetic susceptibility and whatever else is going on. And it it reminds me of an observation of this Tuki Center people who are, I think they're Central Highlands of New Guinea, and they were examined by a research team from ANU and Canberra, I think in maybe the early 70s. And they did, you know, comprehensive analysis of of an observation of their cardiovascular health and found a very, very extremely low prevalence of of cardiovascular disease. These people subsist on a 96% carbohydrate diet. They're essentially extremely low fat, extremely low protein, essentially living on um sweet potatoes. Uh they they have pipe smoking is is rife. And pipe smoking as well? Pipe smoking is is extremely common. And they have very low cardiovascular disease. And I'm not sure if they've got another source of dietary nitrate, maybe in in whatever their kind of uh hope eating. But you know, one of my key observations that I kind of took out of that is that these people would have had a very, very regulated circadian rhythm. They don't have a lot of light at night, and um, you know, they're probably getting a lot of the thermal store release of of nitric oxide from natural sun exposure. So based on based on your uh understanding, do you think that if people are replenishing their nitrate stores diet from the diet, that they're gonna get more bang for their buck from say UVA uh sunbathing?

SPEAKER_01 55:11

No, look, that that will complement it, but there's also another uh gentleman on X called Greg Moosin. Have you read any of his um?

SPEAKER_00 55:18

I've very great stuff. Yeah.

SPEAKER_01 55:20

And then simplicity, he says he looked at the cement, the sardidians, and some have high carbs, some have um just um meat and fat, uh, different diets, and he determined it was this movement. Movement, call it shear stress generation. I could I could translate that to shared stress generation, uh, just for their substance a living. I bet you they don't sit around doing nothing. I bet you they're constantly out working the fields, hunting and and so forth. But um interesting, you know. Um uh and he puts it down to less diet. We know diet that diet matters, but less diet, and this might explain this tribe. Um, apart from their lack of interruption, I haven't looked enough of the circanian rhythms with nitric oxide, and you've piqued my interest, certainly there, and and I will do so. Um, but uh it could be a combination of that and also a combination of of just constantly moving. I mean, interesting, I've got a little fit, but watch, I've got a warehouse, and I try and get out and walk a kilometre a day. I'm 66 years old, and I get my five and five or six thousand steps up. But the other day uh I was in my warehouse and I forgot to have my daily walk, and I was just packing a few boxes for customers, and then I got home in 13,000 steps. So what I really was doing, I was just staying on my feet and moving a little bit. There's no step walking and laps, H-I-I-T, nothing like that, just moving. What I would love to do is next time there's road works on this road, get one of the people with the stop-go sign who think they're not even walking anywhere, but they're staying on their feet a step. I mean, when I was packing these boxes, it's a small warehouse, so it's just a few steps here, a few steps there, but whoa, 15,000, 16,000 steps. So I surmise, I wonder if the people on the stop-go signs that think they're not even doing anything, I like to see how many steps I do a day. And then it comes back to it doesn't have to be running, uh, laps, uh seriously high-intensity training. I'm a bit shy in the HI the high-intensity interval training, noting that most myocardial infarctions are roxas. Uh, I just read often go out and start H I I T, so we get a 65-year-old with um a bit of plaque and so forth, um, gets out there. I I actually used to run a martial art club and then another incarnation when I was young for 15 odd years, and I had one of the fathers of my student, unfortunately, join the training. I haven't trained for years, and he jumped on the mats and did a bit of judo, and he died in a sleep the next day. And I've often thought about that. And then another friend uh uh in Adelaide just sold his house, 50 something years old, hadn't surfed for a long time, went surfing, bit sore, but he thought that was muscular, bit sore around the chest, and he unfortunately passed away in the night. So just two examples of rupturing. So, what do you think about that? Uh about the hind uh I I I think that Greg's uh what Greg uh states is that we can get what we need for our cardiovascular fitness and generating of uh nitric oxide of just moving, staying on our feet and moving instead of sitting down.

SPEAKER_00 58:35

Interesting. Couple couple points to the those who have not exercised, you know, currently or doing high intensity and then passing away. To me, that's that screams of person has got a massive load of soft plaque uh either in the car sitting in their carotids or sitting sitting in the LED, and whether it's you know physical trauma, you know, judo tackle to the neck or whatever it was, and and then they just start plotting and yeah, it's your game over the LED occludes and and they have a massive infarct. So I think what my my takeaway point from that is if someone is has sitting on sitting on the couch for years or decades or months and is trying to do a health kick, I think uh and they have no idea about their cardiovascular risk. I I think stabilizing plaque stabilization should be should be the the goal before we do you know h high intensity exercise. And I mean we we can talk about high uh how do we stand on the well I think it's a lot of what we've just talked about is um and maybe we haven't re you know um talked about the insulin resistance connection, but it seems like as the body becomes more insulin resistant, it diverts or um shunts signaling away from uh Enos. So to me, it would it would make sense to if we want to try to immediately stable plaque. And obviously you and I both know that the mainstream medical approach to this is uh you know hydrostatin therapy immediately. But I think if we were doing it h holistically, it would be immediately get that person into the sunlight, immediately get them into the UVA spectrum so that they can start liberating dermal sores, benefit from all the infrared light, and we didn't we didn't talk about infrared, but I I think up to around 3,000 nanometers seems to be potentiating that fourth phase on the endothelium uh that's the US UVA territory? No, it's it's it's deep into the into the mid-infrared, so beyond the opposite end of the electromagnetic spectrum, that seems to try to separate this water and build a what uh what we what seems to or what Gerald Gerald Pollock has called like a maglev levitation kind of um exclusion zone between the endothelium and the blood contents, which is negatively charged. So if a red blood cell which carries a negative charge and the lipoprotein carries a negative charge, then theoretically it shouldn't be able to get anywhere near the glycocalyx because if the charge is intact, then it they'll they should repel each other. So that that should be sitting above above this this glycocalyx. So if you put the patient in the sun and you provide them with ample opportunity to liberate dermal nitric oxide with an UVA spectrum, but they're also getting infrared because they're that's present at all times when they're outside, and then you do what you're talking about with respect to uh dietary sources like the algula powder. Um potentially you add on ketosis, so they're doing you know the algula powder and all this while in a kind of faster, faster state or keep with nutritional ketosis, you're you're kind of and you you regulate their circadian rhythm and have zero um tolerance for light at night, uh, and you obviously they quit smoking um and and and stressful or situations or emotional stress, then that to me that would probably be the best recipe for plaque stabilization that I could think of. Uh, and obviously we can talk about statin's pleotropic tech effects of people wanting to go the whole hog, but that sounds like a good recipe in my in my book.

SPEAKER_01 1:02:24

But we don't we don't need um uh I I actually think one of the better properties of statin is this plague stuff plaque stabilization than that uh regardless of lipid reduction. But the beauty about it is, and I post I found some great papers I put on recently, which was well received uh on X. Uh nitric oxide, so the so the features of plaque stability stabilizing, of course, is increasing the fibrous cap thickness, changing micro to macro calcifications, and reducing the inner the inner soft lipid and aquatic core. That's a that's a danger. And certainly uh nitric oxide, uh, but nitric oxide also uh uh decreases inflammatory marks in there. I would say side by side that uh nitric oxide, uh, via the Doom or approach and the dietary approach, um, and a little bit of shear stress, nitric oxide can't hurt, one of the good stresses, shear stress, um uh nitric oxide. If I had to choose between one or the other to stabilize PARC, I'd be looking at the nitric oxide reaction. And then I double back to statins and note that they do have a property of increasing X amount of enos function. And I often wonder the small percentage of improvement or the percentage of improvement, absolute risk, relative risk, and so forth. I wonder how much is not lipid reduction, how much is actually uh from their boosting enos. They can boost enos function, statins, not as much as other uh other areas, uh, not as much as much as I would suspect as dermal nitric oxide production, which can also go vascular, as as you already know, uh, or nitrate nitric oxide, but still it's a thing with statins. And I often have thought myself beyond pleotropic, uh, I would suspect that's one of the major actions uh of the statins. But back to nitric oxide, you can stabilize the plant very adequately with nitric oxide.

SPEAKER_00 1:04:23

What what's your take on potential you know, short-term versus indefinite uh dosing of lipid laurine or stat or say statin therapy? We won't talk about the rest of the lipid lauring. Just you know, what what say because you have patients well I I can I get patients on all sides of the spectrum and um position when it comes to to to whether they want to take statin a statin or not, and that inches has an individual risk formulation that we don't necessarily need to go into. But what what what is your take on potentially short-term dosing or temporary dosing, say post-infarct or post-post-MI?

SPEAKER_01 1:05:03

Well, um, and again, it's the patient if you surmise from talking to the patient, taking the case that there's no way in the world they're gonna work on any risk factors, uh, even endeavour to get the enos uh functioning well, or even try this new fingled arugula, I don't eat greens. Uh, if they're that way, well, we might as well go back to the midstream, the lipoprotein retention and reduce. Even though it's only 0.1% of circulating LDL that's involved in etherosclosis, I suppose if we take it down to 0.05 by by um reducing all circulating LDA by 50%, uh, it can be it's still working on an area. But I don't think the bangs for bucks are there are there as well. But and again, it depends on a patient. If they're doing nothing, if they if they're just not conducive to doing anything, the risk factors, the metabolic health, it's still an element, isn't it?

SPEAKER_00 1:06:01

Yeah, and and look, let's make it uh clear in another way, because you know, I'm gonna I'm gonna give an example in terms of risk, because I think it's actually worth uh uh enumerating or discussing for people. Risk risk matters a lot because you have two people at the opposite end of the risk spectrum, and the decision is completely different. And what I mean by that is you you again, you have someone who's in this primary prevention category means they've never had a heart attack, uh, and they're they don't have any family history of cardiovascular disease or or coronal artery disease, and their cholesterol maybe might be six or six point five, they have lean body mass, they don't have any marked. Because of metabolic dysfunction, they have potentially have a calcium score that's zero, they're physically fit, cardiovascular reserve, all the rest. If you plug all their numbers into the risk calculators, they're very, very low risk. On the other end of the spectrum, and this is a patient that I've had, and very strong family history of early cardiovascular disease, raised lipoprotein little A, established cardiovascular disease on calcium scoring with you know uh a soft score of about 800 known LAD lesions and um you know stress testing, they've got some uh uh uh wall hypokinesis at maximum reserve. So you know, you've got you've got two radically different ends of the spectrum. And I think the narrative online in many cases is just you know statin therapy bad or you know, XYZ. It's all very binary. But but what we know from the data is the person that the second person the number needed to treat for statin therapy to prevent one event, I believe is somewhere in the order for that person is below 10, below 10 people, uh, based on certain data. A lot of it done by um Dr. Matt Boudoff, um who who is the leading one of the leading uh I've read I've read a few of his papers. Yeah. And then the other person, you know, the number need to treat is like infinity is infinity because because you know, there's this is just no benefit for that person.

SPEAKER_01 1:08:19

So it can't it can't be a negative, especially now with the uh five milligram uh new generation, uh less uh muscle pain, uh less side effects. The side effects are real, but for that patient there, even as a holding pattern, uh uh I I can see that benefit. Also knowing in the back of my mind that there is a bit of increase in nitrogen. They might not want to eat aragua, they might not want to hop in the sun, but there is a little bit of enos uh boosting by statins and a bit of plaque stabilization. So what you're what you're saying is actually um that's right, horses for horses, of course.

SPEAKER_00 1:08:56

Yes. And and look, some practitioners, again, they're not endorsed by any of the cardiac uh, you know, uh organizations, but I but some practitioners might use ultra, you know, five milligram results in alternate dates. So um I think again, if we're thinking really hard about stock stabilizing a critical lesion that could take out someone's whole um, you know, left ventricle, then that that that I don't think we should exclude that as being an alternative.

SPEAKER_01 1:09:27

No, and and now we're being reasonable, we're not being binary, yeah. And it feels good actually having that flexibility, isn't it? Uh in one's own mind, because you know there'll be people that are no circumstances whether give a statin, or there'll be another category that actually genuine, genuinely, I've even heard this, want to just about put it in babies' bottles from then on.

SPEAKER_00 1:09:47

Yeah.

SPEAKER_01 1:09:48

So it's good it's good to have that um uh insight.

SPEAKER_00 1:09:51

And and and really this is, I mean, the job, I think, the and then one of the cruxes of why a lot of people uh are not happy with how they were presented is that they weren't given the informants, they were given the options. They were just, you know, here's your status, you know, go off and take it, don't ask any more questions. But you know, when it when it comes to uh tools and options, I think that it's that's the most important thing to me, which is just giving giving giving patients options. Um I wanted to ask you a question about do you know if fermenting argula, like bacterial fermentation as if you were making something like sauerkraut, uh, would does that do anything, or have you read any studies if that enhances the I have uh you mean the kabbuchas and so forth? Well well, any form of bacterial fermentation, can that enhance the can we just come back then in a second?

SPEAKER_01 1:10:45

I just wanted to quickly um uh back back to the stabilization. The beautiful thing about nitric oxide stabilizing plaque, it stabilizes plaque whilst reducing calcification. Now we know that um statins stabilize plaque, increase CAC scores, but uh nitric oxide through multiple mechanisms, but that same PGF mechanism directly reduces artery calcification whilst you're stabilizing the plaque. That's interesting, isn't it?

SPEAKER_00 1:11:15

That's that's fantastically interesting because reversal of calcium scores is not something that happens, I don't think it happens often. I mean, I've I've I've heard of people have come to me uh having or or reported sent me an email having you know regressed score with you know lifestyle protocol, which included um you know utilizing that new dermal uh mobile dermal store through through ultraviolet A exposure. But you know, it's not it's nothing that you that anyone can guarantee. So it would be fascinating to to do some more long-term studies about and and see you know to what degree can we get regression. And maybe maybe maybe it's a good time to discuss the stat keto CTO CTA study um with the lean mass pipe responders. Did you did you are you abreast of of that study at all?

SPEAKER_01 1:12:08

I was com commenting on some Facebook page today. Um I'm in a few on a few Facebook pages um reversing calcification, healing uh ethostosis naturally, uh, and on Twitter, and I saw Dave's post um today that he actually um he actually um um explained where we're up to so far. Have you heard the like heard the latest news?

SPEAKER_00 1:12:31

Yeah, yeah. I mean, I'll just quickly stand out so the listeners know what we're talking about. Essentially, Dave Feldman uh and you know Dr. Budoff was you know the investigating cardiologist. They they took a cohort of people who have high LDL, high total cholesterol, and low triglycerides and low and high HDL on it on a ketogenic on a low-carb ketogenic diet, so-called lean mass hyper responders, and they tracked them, they tracked their coronary plaque with with CT coronary angiograms. And w the conclusion of their first analysis, and maybe this is going to change in light of this recent uh development, was that they they they thought that the total amount of or the LDL wasn't correlating well to plaque burden, but it was actually the amount of plaque that someone started with. So uh but if you look at the cohort as a as a whole, and correct me if I'm wrong, Peter, that that cohort still laid down more total plaque than you know uh uh a cohort on a standard American diet.

SPEAKER_01 1:13:36

So, you know No, that that that's where that's where there's new development. So um uh I've spoken to Dave a few times uh on on X, and I don't know him well. I know people that know him, uh, and I see what he's been doing from a distance. And I in the first instance, I think it was honourable doing the longitudinal study uh on Ray's LDL. Um I don't even understand much about the um uh um uh his his um explanation about why uh an an energy model. I've even suggested uh when he was copying a bit of flak there for a while, that um maybe if you um do the FMD studies on it, it might be it might be affirmative. But what I understand the latest comes, this is only today I've read this, a post today, it goes something like this is that he had one organization that uh did the scans and they showed and then he popped a bit of a hard time on X because it showed that uh he had a higher rate of plant growth than other metabolic uh comparisons.

SPEAKER_03 1:14:40

Yes.

SPEAKER_01 1:14:41

Then they did another uh another scan that brought it back to similar uh uh uh similar or less. Um yeah, yeah. Oh, don't forget there was some regressions as well. Um but the news I got today is some of the uh people of the hundred cohorts that was uh the the original people uh wouldn't wouldn't actually um uh wouldn't have another look at the scans. Uh he can explain that better. And so some of the 10 of the actual people the participants via their doctor went back through that same organization and had another look at them, and they were totally different.

SPEAKER_00 1:15:27

Yeah. So so basically clearly, which is a company that's responsible for this AI and the.

SPEAKER_03 1:15:33

Was that the first one?

SPEAKER_00 1:15:34

Yeah, clearly, Clearly does does CT angiography and provides the analysis which allows you to determine what percentage of the plaque is soft versus hard. So I mean it almost starts starts sounding a little bit conspiratorial, but it sounds as if the initial analysis of the data potentially was reported uh erroneously, whether that was deliberate or not, to demonstrate a higher plaque progression than that actually happened. If that's the case, then the first paper is potentially uh needs to be retracted and republished with with more accurate results. But it's only reading what what Beldman, which is the chief one of the chief investigators, published, is that it seems a bit sus that clearly if this is what is true, wouldn't give access to reanalysis and why they're holding that data without uh transparency because that that is that's incredibly sus to me.

SPEAKER_01 1:16:32

Um because the big discovery today, sorry, was um that it that that I took from what he wrote today was what the first uh guys did is they didn't blind it. It came out they wasn't blinded, so they asked to re-look at the data blinded and they refused to do that for I don't know what reason. So he had 10 participants go to their doctors uh and get access to the data, and they were different. They were they were showing regression and and look, I I still don't know what the end result is, but it's uh the first one I think, and he's had it, he's had another one since then look at it, and then yet another uh one that was already preordained, and I think they've brought it back to normal levels of plant progression. Um but when I say normal levels of plaque progression compared to someone with metabolic syndrome or compared to someone with diabetes, uh, but this is with hundreds uh with extremely high uh LDL levels, uh beyond FH levels. So I don't know. I mean, there's enough doubt there. I don't I don't really know what to think, but I think that an FMD of the people that didn't have plaque would be if if they've had long-term uh ketosis, extremely high in Australian levels, we're talking about eights and uh eights, nines, and tens, uh LDL, and they have uh no plaque and an excellent 12% FMD, I've suggested to them either an Enos ELISA uh study would be great, and you might prove that you've got enough that bank again, you've got enough um risk factors low, that is why you're not getting plaque. It might explain it to the world. Uh I've suggested.

SPEAKER_00 1:18:16

Amazing. And and look, that was actually my exact thought, Peter, was when I when I first read the analysis of that C keto CTA, and we saw that this plaque was increasing, and maybe again this result's going to get retracted. But my first thought was we need to be studying those who had plaque regression. I want to know what those who saw regression were doing despite having you know the LDLs of 10. And I think that would give us insight into everything that we've talked about and absolutely assessing their their nitric oxide uh state by doing something like that F uh, what is it, FMD?

SPEAKER_01 1:18:56

Uh FMD, yeah, flow media ventilation, yes. Yeah, FMP. And that can settle a few arguments, I I think. Uh FMD. If, for example, um um X amount of participants uh demonstrating no plug, also had an F and FMD after years and years and years of high uh LDL, it makes us want to look more. Yeah, it makes us not be dismissive.

SPEAKER_00 1:19:21

Yeah, yeah. So I mean, look, I don't I don't want to sit here and um you know throw stones at Feldman at Al. I think they're doing tremendous work for asking the question in the first place. But absolutely I would have liked to know a bit more about uh, you know, those what what were the serum vitamin D levels of these patients? How much sunlight did they get? What was their, you know, what was their light exposure habits now that Dr. Professor Kane has got those light loximeters, we can track people's, you know, light exposures and infer their circadian uh disruption or not. So, you know, there's so many different ways to go. I think I'll have to try and get uh Professor Buddh on my on the podcast and to get his take on it all. But uh yeah, it's it's it's very interesting. Uh there's one maybe there's one edge case that I want to discuss because I think it makes sense um in terms of maybe circling all the way back to this idea of the bank and you know atherosclerosis developing in a healthy blood vessel. And that is the case. Again, I'm I'm I'm I'm I'm taking the devil's advocate position, the you know, the cardiologist position here, which is in homo certain cases of homozygous familial hyperglosterolemia, you get people that are very young, uh, you know, girl, you know, I don't know, 10 years 10 years old, nine years old, developing uh atherosclerosis. Um and then so the question is, is that someone who all other things equal? The only factor at play here is their serum uh LDL level, or uh and therefore that's in and uh enough by itself to develop PARP, or what else do you think uh, if anything, could could explain that?

SPEAKER_01 1:20:59

I don't know. Are we talking about hetero or homo uh uh zygus?

SPEAKER_00 1:21:03

Homozygous. So they've they've they've they've they've basically got both copies.

SPEAKER_01 1:21:08

Okay, yeah. So that's right, and that's the more serious cases than those. And they because of the uh because the other um cohorts, they uh the the other other the other, they actually um have up to like 40 percent with no plaque.

unknown 1:21:25

Yes.

SPEAKER_03 1:21:25

Okay, yeah.

SPEAKER_01 1:21:27

But the um but the but the but the FH with both sides, uh yeah, they can actually get atherosclerosis and MAs at MIs at 10, 12 years old. But but I read there also was some clothing factors possibly as well. I I don't know if you're um you are you up to speed much with LPA?

SPEAKER_00 1:21:47

Well, I mean that I mean we could we could talk about that maybe briefly, but I mean uh uh and to the degree that it's it it the it seems to its effect on outcome seems to be mod modified by the the the redox state. And if someone's got their system full of oxidated, you know, lipid peroxidation products from eating chips from the uh RSL for the past 10 years, that that's probably gonna modify the pathogenicity of the LP little A particles. That's my understanding.

SPEAKER_01 1:22:19

No, it's just come out recently. Uh it's actually Thomas Dayspring that posted the paper uh uh that the main actions of LPA uh L um little PA is actually via um uh uncoupling ENOS.

SPEAKER_00 1:22:35

Oh, interesting.

SPEAKER_01 1:22:36

And we and we've always thought it was a Kringles, which it still is X amount, but the main action is actually uh uncoupling Enos. That's interesting, isn't it? But back to back to the familiar familial uh hyperclastremia, yeah. That's see that's a case, but they've also got major receptor problems, haven't they? Uh but it's also a case that maybe again that back to that bank. Uh LDL can be causal if it can uh deplete the bank enough, uh, and that might be the biggest deduction that one can have from the bank. Uh, an example.

SPEAKER_00 1:23:14

I just think it's disingenuous, and I've had debates with cardiologists on X, to use the example of that, you know, homozygous FH child as a reason to, you know, justify this primordial prevention of you know keeping LDL as low as possible from as young as possible, uh, in a in a patient who otherwise wouldn't, and I guess you're never gonna know because you don't we don't have a control to run against everyone's life. But uh I think there has to be a I guess a common sense approach here and obviously patient setting decision about who should get satin therapy and who where who shouldn't. And and obviously let's like let's look at what other factors here are driving park accumulation across the lifetime. And I think we've made a you've made a pretty good case that that Enos and nitric oxide is is is key.

SPEAKER_01 1:24:10

Yes, uh yeah, look, and and uh it's it's not the best comparison. It's talk talk about car crashes and using the most extreme example, you know. Um those seat belts, ball tires, everything, you know. So don't drive cars because they crash. Yeah, we can't use that example, you know. And so sometimes uh extreme examples uh can make one's point, but I think I I agree totally. I think um stat staten or lipid low therapy for the for the uh masses shouldn't be decided by uh FH cases. Yeah. Even some of the mice examples, they feed them a fatty diet. People can argue would they normally eat that? They've also the knockout mice, APOEs and so forth. Um that they're more good to actually uh try treatments and so forth rather than actually to find to talk about etiology, I I I suspect some of these mice ones. But also, um yeah, also for different reasons.

SPEAKER_00 1:25:11

Um yeah, so um talk about the I just want to read I just want to creep read a quick excerpt from the paper that you referenced to me. Uh, and this was in reference to what happens if you knock out this enos gene from mice. And it says Enos gene deficiency results in hypertension, increased vascular smooth muscle cell proliferation in response to vessel injury, increased glukocyte endothelial interactions, hypercoagulability, and increased diet-induced atherosclerosis. So there we go. There's um that's what happens if you don't have functioning enos.

SPEAKER_01 1:25:45

And and now, circling back onto the glyco glycocolics. That glycocolics impaired. So you basically what I was saying is I believe that the um uh the thinning, the setting, uh, the permeability of the glycolyx is a factor. I just think that it's my only difference is I think it's downstream, uh, and maybe I think different than other people, I think it's downstream from uh enos uncoupling, where others might say, no, no, that happens first, and then we don't get that Enoshare uh stress-generated um uh nitric oxide, which depletes nitric oxide. But the example I will use um uh was actually that, one of those ones. The Enos knockout mice, do they have an impaired glycocalyx? They don't really look at it. I've had a look, they don't really have a look at it, but straight from the word go, it shows that uh Enos um uh lack of function is directly related to all those manifestations. Secondly, is what is the damage of the risk factors in the glycolacs? Smoke particles, certainly, AGEs, um, uh physical forces uh from uh hypertension. But now let's go to other risk factors for heart disease, obesity, stress, lack of sleep. Uh uh, I would posit that there would be minimal damage to the glycolyx, but those other risk factors I just named are all complete denos. And so uh, what what do you think on that point? I mean, I'm and I'm having a couple of discussions right now uh with David Diamond on that point. He also favors the uh lack of glycolx first, uh, and then that creates more entry into the subendothelial space and so forth. But it was also saying before, entry into the subendothelial space is not retention. Otherwise, we're falling, uh, we're also falling prone to saying high cholesterol always equals heart disease, high transitosis also always equals heart disease. No, it doesn't. It has to be returned.

SPEAKER_00 1:27:56

That that that doesn't make sense to me. And and again, I'll I'll hammer home the point that Stephen Hussey raised. He did an excellent talk again and specifically with respect to this fourth phase water that's this gel gel-like phase, which is sitting above the endothelium, and it's exclusion exclusion, exclusionary, exclusive of anything uh larger than a potassium ion. So, you know, by no means is a red blood cell or an LDR particle able to get near the subental intermilch base if that fourth phase water, which is sitting above the the glycocalyx, is um is intact. And um the the study that's worth reading, Peter, is uh it's it was written by Polak and his one of his PhDs. students.

SPEAKER_01 1:28:42

I'm not great at giving us it's not I'll send it to you.

SPEAKER_00 1:28:45

It's called on the driver of circulation, on the driver of heart circul above the heart, what whatever it is. And they essentially use infrared light on a chick embryo model to show how that light input is actually creating this exclusion zone and and facilitating blood flow. And look, that's another whole story about cardiac physiology and the idea that the heart is not just a meat pump as we're kind of led to believe but it's it's probably this essentially a band of myocardium that's this vortexing that's that's having this very uh you know probably like the hydraulic RAM effect rather than just you know a pump. But you know that that's another whole topic to talk about.

SPEAKER_01 1:29:30

But but could that be the first uh could that be the first stage of endothelial dysfunction after uh enos uncoupling?

SPEAKER_00 1:29:39

Also a third thing I forgot to mention is that um uh nitric oxide inhibits uh many shedding enzymes interesting it might even be a re I mean it's obviously it's a reciprocal relation whichever way we look at it and both are involved uh lack of enos and the shedding and thinning of a glycocalyx but could the uh could that be stage two after the enos is uncoupled then that allows uh uh the um glycocalyx to be compromised uh absolutely I mean in my book you've got to you've got to impair the this this gel this fourth phase of water this exclusion zone by you know chronically staying indoors and getting deprived of natural daylight and infrared light grounding essentially put in contact with the ground seems to also potentiate the this exclusion zone so you know you immediately take away two foundational inputs of ancestral inputs of how humans operated and then the exclusion zone drops and then you've potentially got this uh opportunity for the glycocalyx to get impaired and then the Enos to get impaired so yeah I think all that the the the story of atherosclosest as we're talking about it's mostly this upstream story if you've gotten to the stage of the life you've you've it's it's like coming in at the last five seconds of the movie. I mean the whole the whole movie beforehand was that was why that person got where they were and then uh through all these pathways that I think we've discussed.

SPEAKER_01 1:31:09

Yes that and that's why I wrote that little ditty recently uh uh on Twitter on on X Now as well is that some people may mistake the absolute necessity of LDL to be involved in lipoprotein retention midstream to be the sole cause upstream. Yeah and say one of the factors in the bank. But would but does that sound logical to you that um so agreeing totally what you're saying about the glycocalyx and all its properties and another gentleman sent me some brilliant photos of it magnifying of it impaired apparently it can repair itself pretty fast as well but I I just I I just at this stage on banking on that the enos bank uh the enos has to be depleted before the glycocalyx is compromised um say the other way around where many people would say no no you only get uh the glycocalyx first and then you're getting less shear but shear stress generated enos is not the only form of uh nitric oxide in the body as well I don't know but look I'm open to learning on that one it's uh both of them are involved both of them are upstream from the midstream lipoprotein retention I'm just trying myself to learn and get the correct order of those two in place.

SPEAKER_00 1:32:24

Yeah it's uh I mean I don't think there's no clear answers yet but I think we've discussed a whole bunch of very exciting pathways for investigation and look as as a as a clinician on the front lines of athosclerosis and and and I guess you could say fighting the disease to have real-time indicators of vascular health with something like this FMD rather than relying again on what sometimes feels like this tea leaf reading of uh you know lipid panel interpretation or waiting for a calcium score which is only giving me a backward facing indicator of you know what 60 years of that person's you know vessel injury and and and and healing capability like these are all it's it's not ideal if we're trying to be at the cutting edge of of prevention of of of this disease. So um yeah let's let's let's uh hope and with there's more tools in the toolkit soon to for doctors to um you really get to the heart of what's causing this.

SPEAKER_01 1:33:24

And I think you I think you'll get them uh before when I when I'm saying uh the estimates uh five to six years to be portable there's one I was going to buy my own actually there's an endopat one uh that's a reasonably portable one no nowhere near the public can have in a smartphone and so forth but I suspect that you will have one as a physician uh a couple of years before others do and then it's a game changer you can uh you can get a bet better assessment immediately on the real effects of all the risk factors and the treatment improvements uh and the supplements and so forth uh in real time on actual um even secondary patients to stabilize and dare I say uh regression's hard a little bit of regression but stabilizing uh the plaque's a bit the big thing but uh for the for the early um many people have no don't even have fatty streaks at a more advanced age so there's it'd be nice in the in the 20s in the 20s the teens and 20s to concentrate on the prevention side still with FMD available instead of instead of seeing them in 2030 years time.

SPEAKER_00 1:34:34

Absolutely so maybe to finally to wrap up Peter if you could just summarize in in a very short amount of time again a little bit about about Enos and what what can people do? Like we've we've we've talked about for about an hour and a half or even longer um what what are your key kind of insights or takeaways for people if they they want to preserve their blood vessel health and to do everything they can to prevent heart disease developing the coronary arteries?

SPEAKER_01 1:35:01

All right uh and and starting backwards uh you would have read that EPA um uh studies overseas uh plaque stabilization and mace but people don't realize uh DHA is underplayed and and if I was a conspiracy theorist I'd say it's amazing just when there's a brand new uh VAS keeper medicine out I think I was the first one in the country to get a prescription because I've been watching waiting for it to get for the TGA uh the Baskeeper um EPA only no DHA if I was a conspiracy theorist I'd be saying hmm fortunate timing just when I've made the first EPA drug studies come show out that that DHA compromises EPA but the more you delve into it DHA is all about endothelial function and proven not that EPA can't do. DHA is the one that actually reduces all the inflammatory markers and so just starting backwards on on endothelial health I think um uh DHA a good dose of DHA both yes sorry Peter's referring to to contrahectanoic acid which is the omega-3 fatty acid polyent fatty acid which is enriched in seafood uh and and so um uh without getting their brands or anything too much but we're lucky in this country there's a triple strength uh fish oil capsule that it's easier to have a half a dozen and bring up to the dosage levels uh of some of the best keeper trials of the EPA and having a DHA and then I think you've got uh and I and I personally don't believe uh that the DHA does cancel out the EPA I think it's I think it's complementary. And then information is also noted now to be uh starting to be more accepted. I think they have uh I think Bud Off as well was involved in that trial with culture scene um showing uh plaque stabilization um uh slow rate of growth of plaque um there's a great patented form of Kirkman and kick around the world and all the top uh manufacturers are now dumping what they already had and swapping to this patent. It's called the Mariva patent and it's the only one that survived multiple studies on inflammatory markers on the interleukins uh TF alpha uh CRP ESR and so forth and as opposed to culture scene lipid peroxidation markers as well it's um that's out there as well so uh the EPA DHA high dose and the Ker com in for the uh for the Mariva patent I mean Thorne's adopted it one of the top brands in America uh I think New Life a local uh brand in Australia has adopted it's readily available uh but but the but it's the Mariva patent it's there's no black pepper involved to try and get it um get it in and then come back to nitric oxide um uh as we started I I I I believe that if one could maintain youthful nitric oxide levels uh the chemistry required in the endothelium to initiate and proliferate a lipoprotein retention athroscosis uh could uh be negated and um and not start or not proliferate. Um recoupling ENOS that's the whole eadrail um bH4 there's been a few studies on BH4 which it has done well uh every time uh all all the risk factors in a essence uncouple ENOS all of them by um including disturbed flow areas as well uh they they all um uncouple uh including aging uh including hypertension smoking everything else by oxidizing BH4 and they are trying to you can get a prescription form of uh BH4 but it's been ambiguous to studies but the newer way of looking at it is probably because they should have had more cofactors with it. So folate's an important one folate really stabilizes so before going back to talking about um uh the dietary nitrates nitric oxide and citryline it'd be great if we could actually recoup our enos there's a great study uh great few papers out in Bethylenic acid which is um uh a birch tree extract uh that's actually only a mice so far but that's going very well on its own as an agent as a sole agent on recoupling enos and increasing its function uh its expression and recoupling it but so if I was trying to get overall health um for the arteries briefly alluded to EPA D H A Mariva whatever brand it is look for that patent of curcumin it's great it's outperforms culture scene but surely is doing well as in Buddhist styles but outperforms and all the inflammatory markers then I'd be looking at folate because folate can stabilize and stop uh BH4 from oxidizing ascorpic acid uh as well uh just general uh random oxygen species antioxidant so I'd be uh adding those to the repertoire uh and then be looking at um uh acitrilline which is three times more effective without the gastroupset of arginine for the Enos pathway to make nitric oxide and then try and get four to five hundred milligrams uh of um dietary nitrates in you can find beetroot powders they sell one locally in the uh local health food stores in our area uh surprisingly it's the strongest one I've come across in the world they're usually only about 2% but here in the Wollenbar back it's a locally made brand um uh 5% uh nitrates but again too much um oxalates uh to you probably have to have about 150 grams of uh araguola to get that nice dose you want but you can get aragua powders and you can find them on um Alibarber and so forth and uh it wouldn't be hard to make your own to buy a ton of it and dry it out yourself and make your own. I think that would be preferable to buying it on Alibaba if I you don't know what you're getting when you when you uh some you know Alibaba theme I do a lot of scan scans for my other work and Southern Cross University uh a lot of scans and so um like sitting right here now I can pull up one two three four from China you don't know one's really good but the other three or four you don't know what you're getting. Yeah so but um but to find uh it doesn't mean that a local manufacturer couldn't make it because it's relatively inexpensive aragula so an uh an aragula or just um deferred uh araguula celery uh sp if you have moderate amounts of beetroot moderate amounts so you're not going to get too many oxalates in it and by the way if you're having um a lot of beetroot just flow the oxalates in the rest of the diet just just to uh just to come to it but dietary nitrates um celery aragule favored then spinach then beetroot uh it wouldn't be hard to have enough of those every day like the DASH diet to get up to the required 400 milligrams then between three to six grams of citrulline and I think that's uh between the citrulline uh dietary nitrates for the nitrate to nitrate oxide pathway and the cofactors of folate and ascorbic acid that'd be a really nice combination uh some some estimates of the ascorbic acid alone can increase uh citrulline and dietary nitrate's uh output of nitric oxide up to 20% or or uh and uh put you in the same category as the little blue pill but without the uh little blue blue pill yeah and look uh as we know uh on XNAL many uh many people researching uh and discussing uh cardiovascular disease are taking uh I'd probably name a quick 20 quite easily of I follow who follow me who have actually uh for quite some time people I respect taking um uh every second day five milligrams of cyalis uh and uh there's sound uh there's sound reasoning behind it as well uh I think they now have some actual studies out supporting it.

SPEAKER_00 1:43:37

Yeah. And um you didn't mention but but activating your dermal your dermal I was just to come back to leave it to finish part part off to yourself. Plenty, please get get your get your skin in the game, I think and and again I'll maybe I'll reference with Richard Weller's research in the renal transplant patients and then they noted depending on the latitude the the more UVA light the more UV light they were getting the lower the blood pressure um went. And the effect was attenuated in African Americans meaning that the more melanin you have to dissipate that UV light, the less therapeutic phasodilation you get. So um you know light is uh having an anti-antihypertensive effect through this nitric oxide source. So uh yeah yep get get your skin in again.

SPEAKER_01 1:44:27

Yeah look I I'd I'd appreciate if you actually sent me more uh links I'd like to um study up more on the on the dermal side of um of nitric oxide.

SPEAKER_00 1:44:36

Of course yeah happy to well um thanks thanks Peter this has been a very interesting conversation and uh we we went down a lot of different rabbit holes but it's refreshing to talk to someone who who isn't um you know just about lipoproteins and uh refusing to engage in in any other or entertain any other ideas. So you're you're very open-minded and I really appreciate that. So yeah thanks uh for the conversation and um yeah look forward to seeing like the the data evolve and and see what else we can do to help prevent heart disease because I think that's that's why we're why we're in this game you and I.

SPEAKER_01 1:45:14

Yes totally agree and look and thank thanks for inviting me on and uh and I'll and we're sure that we'll do it again and uh this will be this will be an evolving conversation.