Tue, Oct 11, 2022 4:55PM • 1:45:16
SUMMARY KEYWORDS
plasma, cholesterol, brain, halogens, levels, cells, amyloid, choline, acetylcholine, tangles, dementia, neurons, alzheimer, membrane, methyl transferase, talk, system, high, neuro, function
SPEAKERS
Bill Clearfield
00:30
How’s everybody doing? Good having the time of our lives
Bill Clearfield 00:37
as always,
00:38
Amen. Good to see y’all so,
Bill Clearfield 00:47
so can Andy is can you hear me again? Joe, can you hear me? Yeah, sure can. Okay, Steve, can you hear me?
01:03
I mean, Stefan Yes. I can hear you.
Bill Clearfield 01:05
That’s fine. Yes. Okay. How about Kent? Can you hear me
01:13
he looks frozen. Yeah. Yes Yeah, yes reclaim so try that again. Can you hear me?
Bill Clearfield 01:39
Yeah, gotcha.
01:42
What was that about Andy? Yeah,
Bill Clearfield 01:44
the Andes hockey in China to go to Ole Miss. I said Are you out of your mind what I want to go there for? It’s not easy to get to get thrown out twice in six weeks by the AOA? Hey, that could be a world record.
01:59
I think that is a world record. I think you need to get a plaque for that.
Bill Clearfield 02:04
I guess some sort of statue.
02:07
So I think we should work on that board. Yeah.
Bill Clearfield 02:13
So so we’ve been offered some time with Noma. This third week in January in South Lake. We can we can join that join up with them and they’ll they’ll they’ll sponsor us and we can do the do credits. We’re still good for the AMA credits. If I ever get myself get around to putting everything together, I guess after Oh man. I’ll try to
02:41
at least what is the state’s again?
Bill Clearfield 02:44
Nevada osteopathic medical Noma. What are the dates? It would be January. Its January 25. To the 28th.
03:02
We’ll see. We’ll we’ll we’ll be there.
Bill Clearfield 03:05
Okay, so so it you know it’s an offer so
03:12
and that way we’ll have a
Bill Clearfield 03:17
hopefully a little bit bigger audience so I’ve been there and then went into what they do what they do. They they have classes like from 7am to 10am. And then they go skiing till about four in the afternoon initially, and they go, go, Gordo. They come back around four and go to seven. So
03:36
that’s not a bad schedule.
Bill Clearfield 03:38
Yeah. We’re waiting for Dr. Diane.
03:46
From that Alzheimer’s
Bill Clearfield 03:53
Doctor good. No, I was just listening.
03:55
So it’s going to be mainly listening. I’m working in the lab. Yeah, that’s fine.
Bill Clearfield 04:03
We all listen. So So in the meantime, how’s everybody doing? Good. Okay, we don’t have our speaker
04:15
yet. So you’re a Phillies fan
Bill Clearfield 04:27
well for Philadelphia, baseball doesn’t really interest me all that much.
04:32
Well, the Eagles are doing good too. So yeah,
Bill Clearfield 04:34
yeah. Well, again, you know, our team is going to be half half, half another team next year. So I know. We’re all just a big bunch of spoiled babies. I think you know, so I don’t really care although I so I did put 100 bucks down on the eagles to win the Super Bowl in September before the season started at 25 to one. So I wanted and I did that in 2017. I put that was 40 to one but I only put $20 down not that everybody hears all that interested in that so I’m not sure where our speaker is. So Dr. Burgess you have anything to share with us?
05:21
Oh yeah, everything’s good. They approved our hemp crop, which is pure CVG. The state approved last week so we got a supply so that’s good because we’re doing what else is good. Yeah, everything’s fine getting ready to try to pull some things off. We have some other people from the outside who are interested all on one doing good deeds. Oh, and anyway,
05:55
so where’s your crop at
05:57
that’s drying right now. Give it another Oregon or West Virginia in the humidor. Oh, okay. And we’re trying to deal with the best processes I’ll speak with you can about it. Some are saying freeze collection which means you let it freeze below zero and shake the plant to knock the trichomes off. What do you think?
06:23
I don’t have enough experience working with it. So you’re talking about acres, right?
06:30
No, we just did experimental this year with 300 healthy plants.
06:35
Really? That’s that’s much more manageable. Well, we have speaking you know to Rhea ran a bunch of acres. Yeah. Shoot a text to her.
06:50
I will I get
06:53
what do you guys what are you guys growing
06:56
CBG G hemp.
06:58
Okay.
Bill Clearfield 07:02
So our speaker has arrived. Yeah. Dr. Good now thank you so much for being with us.
07:07
No worry therapy couple minutes late. I paid for that.
Bill Clearfield 07:11
That’s okay. We get we get to banter back and forth. So we are our group is a combination of the American Osteopathic society rheumatic diseases and a newly formed integrative medicine. We’re here every Tuesday night and we’ve been doing this for almost two years now. And we are the bad boys of the AOA. In fact, they’ve thrown us out twice now in six weeks, which is quite quite a feat. So we’re kind of we’re kind of proud of it. And we’re we’re soldiering on, in spite of the bricks and rocks thrown at us. So usually,
07:52
so what’s the issue what they do, you’re covering?
Bill Clearfield 07:57
The probably Yeah, the front issue is that we strayed from our mission of rheumatology and auto immunity. The back mission is that there’s there’s been and Dr. Burgess can speak to this better than me. There’s been bad blood between people long before I came along the scene and, and people in our group and some of the so called leaders in the AOA so they found that in the middle of the night, they found a reason they just they just decommissioned us. And you know, the more I look at it the more hypocritical they are, but we’re soldiering on and we will we will, we will do our thing with them or without them. So,
08:50
yeah, the autoimmunity and just basically there’s so much more going on now in terms of,
Bill Clearfield 08:56
well, they they specifically cited just you might find this interesting, two lectures that that we had at a conference, and but by the way, they were both mine. One was on the endocrinology of autism and the other one was on traumatic brain injury and they decided that that was out of bounds for a rheumatology and auto immunity conference. Which is kind of ridiculous because those of you who’ve attended those classes know that we spend a lot of time talking about cytokines in neuro inflammation and, you know, all sorts of
09:33
other bullies Those are, those are both autoimmune disease. Yes,
Bill Clearfield 09:36
yes. We do know that. Yeah. And, yeah, and, and then real quick, you know, it was after the fact they found one of one of the other groups, the rheumatol, the neurology and, and psychiatry group, their their program for 2020 was they told us that we were substandard even though they had given us a five year accreditation. The same day they gave us the accreditation they’d letter with for accreditation, they decided we were substandard. The rubric the the Psychiatry and Neurology group, their their 2020 program was asthma, OBGYN. What to do on an airplane, if you’re a doctor and somebody gets sick, and stuff like that. Had nothing to do with neurology or psychiatry, so, but we’ll soldier on. So thank you so much. You’re very welcome. Thank you so much for being with us. We’re anxious to hear from you usually, will let you introduce yourself to the group. If you have slides. Just share it down here. Yep. And, and, you know, take it away. And we usually folks will put questions in the chat. If they have it. We’ll go over them at the end. We try not to interrupt you because, you know, it gets to be a little you know, a little disjointed. We’ll do questions and answers at the end. And we do like to record it if that’s okay with you. We have no prob oh, by the way, we were accused one of the accusations as we were so we were so inept. We didn’t have a website, which we’ve had for five years because I’m the one who runs it. And I paid for it. I know it’s there. Yeah. And all of our all of our programs are on there. By the way, all of our Tuesday night programs are on there and all of our conferences are also on there that on the website that does not exist, that aos rd.org. That does not exist, by the way. So if you’re if it’s okay with you, we’ll record this. Okay, and I’m going to do that now and we’re gonna take anyway.
11:53
Okay, well, very nice to meet all of you guys. I’m going to give a talk on plasma halogens and neurology and aging and death basically. And it goes on in many different categories and they focus on because plasma ologists are kind of a story that most people don’t get a chance to get experience of. And I’ll be having different talks later this year that talk more about early childhood development. myelination. And how that interacts. Basically the same thing happens to us late in life, but what I want to go through is kind of the big hammer issues, and then feel free to interrupt and discuss as we go. Recording is good because it gives you guys some there’s usually pretty information, intense work on this. So let me get to the beginning of this thing. Look what doesn’t help much. Let me going backwards is not usually the easiest thing to do. Okay, so I’m gonna talk about his plasminogen therapy, cognition and mobility. Obviously things that are important. They also have a big important component to inflammation that you’ll you’ll be interested to know about Melvindale died catalase function and so on. It’s about longevity and maintaining function as we go forward. So my background is actually in psychiatric medicine. I’m also synthetic organic chemist. And over the last 30 years or so, I’ve been focusing on the biochemical mechanisms disease. So as I learn more, I tend to learn more and more how stupid I was younger and I’m trying to get a bit more intelligent as a as they get older. But we learn from just empirical data, vivid, technological, non targeted metabolomics and this is what allowed me to look into the biochemistry in much greater detail and then because I’m a chemist, we dealt with biochemical restoration molecules, and plasminogen precursors are a critical component of that. And a lot of diagnostics, in terms of Alzheimer’s, Parkinson’s cancers and so on. Wrote a book last year, still very relevant in Alzheimer’s goes through that in great detail. Some of that I’ll go through today. And then I have a company called program sciences where we do blood testing and supplements. And then we’ve just opened up the Research Institute here in Temecula, where we’re doing much more clinical trial work and case study with with doctors so a lot of education. So that’s kind of background so the book is in pretty good detail. It’s written from both layperson but also a scientist, but detailed lectures on the different components of Alzheimer’s neurology pathology, as aging is there so it’s kind of a deep down the rabbit hole as you wish to go. So the goal here is to learn how the loss of membrane integrity and we kind of we take a lot of basics for granted. There’s two things I talk about a lot of is the energetic balance, like the body generates energy, it burns hydrocarbons in new carbon dioxide and water and uses that energy to charge a battery called her electron transport chain. And that is a critical core component. The other one is membrane structure. It’s what gives a body it’s compartmentalization separates our heart from our lungs from our brain, but it also gives us compartmentalization in our cells. And sometimes we take this for granted but it’s a core component of, of health. I’m going to talk a little bit about that. And so the issue here is some cold hard facts about brain health and death. Because as our brain goes, basically our survival goes as well. The we talked about dementia we’ve a lot of it gets grouped into this Alzheimer’s and related dementia. But Dementia is a fizzy, it’s a symptomatic phase. It’s measured by performance, my memory, my executive function, you know, orientation with space and time. And the symptoms of dementia are very very similar, regardless of whether it’s an Alzheimer’s type or vascular type or Lewy body or frontal, temporal, frontal temporal lobe have slight nuances, but dementia is fundamentally reduced mental functioning. And so we’ve done a lot of long research and so this is a clinical trial for Rush University in Chicago. And it’s a
16:36
quite a large study. So we’ve measured almost 9000 blood samples over the course of 14 years. And if you take a look at the last six years from the last clinical visit, it’s been going on many, many years. We go backwards in time, how many people are still living, how many people have died, post mortem analysis and so on. And we get a final dataset of 1262 subjects. And this is what breaks out to where we have two blood samples taken in these individuals in which the average time between the blood samples is 3.7 years and then we have a certain amount of people with clinical dementia. The average age in this group was 81 years old, visit 185 years old in visit to and we look at just simply the prevalence of dementia cross sectionally within this cohort of individuals based upon the blood lead levels of plasma halogens in their blood, and plasma origins of these essential phospholipids that are part of membrane structure. It’s also a critical component of premature babies. It’s involved in plasma collagen of breastfeeding, it’s one of the highest concentrations of plasma allergens in our world is in humans, breast milk, which not It’s not present in cow’s milk so this is also a high issue with breastfed babies versus formula fed babies. But here, each standard deviation each bar represents the standard deviation of the population. So this is the frequency 600 People 400 to one so it’s not a small study. And this is the percent of dementia in that cold in this bar relative to their plasminogen levels. And you can see with each increasing level of plasma halogens, the percent dimension that population decreases, such that those with high levels of plasma origins have very low rates of dementia, and those with low levels of plasma allergens have very high rates. And if you plot this probability of dementia over the course of their age, you get these three lines. People with high plasma halogens, the top 10% versus the lowest 10% versus the median. And what you’ll notice is that a 95 year old with high plasma halogens has the same probability of dementia as a 75 year old with low plasminogen. So we’re dealing with a 20 year differential in mental health of these individual based upon a critical lipid that goes into our brain and our rest of our body or lungs, in our heart, and so on. The trick with plasma halogens is that we get very little different from our diet, most almost entirely synthesized internally. And if we look at this transition from those individuals that visit one that had no dementia, so there were 77 with dementia, and then 226 So we had these 149 new cases of dementia in this 3.7 year follow up in his elderly population. Well, the transition, the probability that a non demented person will become demented in the next 3.7 years is also highly dependent. Okay, it’s 20 year difference. Okay, so the probability that a 95 year old that has no dementia will become demented in the next 3.7 years. Okay, if they have high levels of plasma halogens, versus a low levels again, it’s a 20 year differential. And when we plot this we get rid of anyone who had dementia at baseline and say, Okay, we track these individuals for six years. What is the Kaplan Meier graph? And this is those that are in the top 15% Roughly, okay, there’s 123 subjects here. It’s basically flat line, none of these individuals get dementia versus the rest of the population shows it here. And this is a comparison of high plasminogen versus the rest of the population versus the three genotypes. Okay, April we to a group of three and four. So, the most powerful genetic risk factor or almost any disease that was measures this presence of the APL before genotype, and you can see the negative effect of the AP for is small in comparison to the positive effect. of high levels plus Mallesons. And we look, it’s an 80% lower rate of dementia based upon the plasminogen levels in their blood. highly significant. And if you look at this SERENDIP like I wasn’t planning on looking at this in detail, but since we had the study’s been going on a long time.
21:23
Since the study ended 557 subjects had now since passed away, so we can actually look at all cause mortality. Now this is the probability of dying in the next 5.3 years after correcting for cognition and the risk of cognition and mortality. And you can see, it’s even more striking. So the plasminogen association which I’m going to discuss in terms of mental health also affects other systems because the all cause mortality difference is actually greater than the cognition difference. And so that an ad if you look at 85 year olds, an 85 year old with high plasma halogens, okay had almost had more than an 80% chance of making it to their 999 us birthday, whereas an 85 year old with low plasma halogens had about a 70% chance of dying in the next five years. So this is a pretty these error bars here and 95% confidence intervals. And so, the take home message here is clearly that these plasma halogens are are related to some core physiological components of human life and we look into the brain. So those that’s all measuring plasminogen levels in the blood, but if you do post mortem analysis in individuals, that we had very strong cognitive status prior to their death, and so we have 100 individuals here, we’re looking at the temporal cortex and these are individuals prior to their death, that they had their cognitive center and no cognitive impairment, mild cognitive impairment and Alzheimer’s disease, their pathology using the brach scale, as well as a C read scale. And you can see they’re quite evenly distributed. That pretty comprehensive analysis of the biochemistry of these brain samples. And what happened is that the association between the levels of plasma halogens in the brain and cognitive status is quite strong. So this is the difference between low plasma low brain levels of DHA plasma which is the mega three version, okay, this is this is DHA is arachidonic acid, linoleic and OLED and we see this very, very strong association with increasing levels of plasma halogens in the brain, increasing levels of cognition, or vice versa. And we look at the known variables of associations with reduced cognitive functioning in the elderly. The AVP for genotype is a big player but AP for genotype is associated with higher levels of amyloid in the brain. So if you’re an e4 carrier, you’re more likely to have elevated amyloid in the brain than a non e4 carrier. And amyloid is somewhat associated with tangles, but if you know the tangle density in the brain, then the amyloid is no longer statistically significant in terms of its association with cognition. And this is why this whole amyloid hypothesis and Alzheimer’s has always been a fallacy. We’ve known this for 30 some years now. But if we look at the association with cognition, the DHA plasma halogens, tangles CHD sensitive choline high affinity transporter to selective biomarker of cholinergic neurons, and flow Killen which is a marker of lipid rafts of where the beta secretase exists, so membrane structure, so you’re dealing with that’s what it comes down to when we when you do this multivariable analysis and what’s left after all of this, you get these four variables after adjusting for age, sex and education, genotype and so on. The plasma halogens for every standard deviation, increase in plasma halogens, there’s a five fold reduction in probability of dementia. tangles is a two fold. And so you can just see the relative scale of these these effects. And so brain plasminogen and cognition and this is I’m not the only one who’s shown this. There’s many many studies have shown this that levels of plasminogen in the brain are highly associated with cognitive performance. So it’s a membrane lipid. flotilla is a membrane molecule. Colon high affinity transporter is a biomarker of presynaptic acetylcholine vesicle density and I’m going to get to that in a few minutes. And tangles are actually also a biomarker cholinergic neuron integrity and methyl transferase reserve capacity. So methyltransferase is an invention that is another core physiological component of inflammation. That’s specifically in in membrane maintenance
26:21
which leads to plasminogen precursors. And so I presented this back in 2007. This is when I first discovered this association between plasminogen levels in the blood and cognitive performance. I went through and did a very thorough international collaboration with people in Japan Case Western, Sun City, and so on. To look at this in many, many aspects of it, so I won’t go through it all in detail, but bottom line is a peripheral metabolic efficiency at all stages of dementia of the Alzheimer’s type. And it precedes the clinical manifestation. Which, you know, led to this bigger concept of plasminogen deficiency mediated diseases of aging. So the old timers in the cognitive impairment is somewhat of a canary in the coal mine that says, Hey, have one of these weak signals as we get older, and it’s the cholinergic neuron is gonna show you the weakness of that cholinergic neuron and it’s also the neuromuscular junction. So that’s why sarcopenia and, seismologists go side by side and so the question becomes, how do we replace these plasma options? And it’s not like we’ve they’re not brand new. We first discovered plasma origins in the 1920s. We know there’s rare diseases in children that have genetic mutations that prevent them from making plasma halogens and these children rarely live to age 10. So high degrees of mortality early in life. So the obligate nature of plasma cells is important. But restoring them turns out to be a bit of a pain. It’s hard to get restored. And so I never got myself involved in this until in the mid 2000s, when we saw this association and through trial and error, this concept of an alkyl ACO glycerol, was really the missing link between ability to intervene into the biochemical system of plasma which is kind of the way l dopa restores dopamine in Parkinson’s. We don’t give Parkinson’s patients dopamine because it doesn’t get to where it’s supposed to. Go. But we want a precursor that can get into the cell system. And that precursor turns out to be this alpha release of glycerol and it can restore plasma halogens in and Ralph these are rcgp mutated cell line that can’t make plasma antigens. So it restores them. And so there’s two types. Plasma halogens. One is for function deals with the neuromuscular junction and the synapse, and I’m gonna show you that the second one which is actually probably more important to core human physiology and what’s important to early infant development is the Omega nine oleic. Acid version, highly relevant your myelin, your Schwann cells. And that’s one of the key aspects of myelination. And that’s what happens later on life. We start losing brain matter, mostly we lose it white matter first. And so we did a clinical trial. It’s been all this is all published in this post mortem. That’s all published as well, this last year, but we looked at this plasminogen precursor in Santa Monica using clinical trial with Dr. Jordans team there. And basically we did the following We took baseline, we gave them one meal per day, which is 900 milligrams of plasminogen precursor for the first month, then we did two months at 1800 milligrams or two meals per day, then a month at four meals per day. Okay, then we had a washout period and we wanted to look at the oxidative stress biomarkers, we want to measure cognition performance, as well as mobility. So these are people that had these were individuals that already had mild, they had cognitive impairment. And what we found was that as predicted, because we’ve done extensive animal work in these these systems, is that we got a dose dependent increase. So from baseline to month one at the lower dose, the moderate dose increased at the high dose, and then after a month, the Washington came back down again. So we get this dose dependent increase and we can we can target specific plasminogen subtypes which is this, in this case, it’s the Omega three DHA. And that can and it’s even more pronounced if you if you baseline normalize it everybody. And what we found was actually quite interesting. Is that the individuals that have the highest level of cognitive impairment, so this is CDR level of two. So this is moderate dementia, there’s no ambiguity with the CDR two CR one and then we had a whole bunch of people with MCI or or moderate levels, but within a four month period 75% of people that had clear Franc, cognitive impairment improved by an entire score
31:19
and their mobility improved, so the sit stand rate for the sarcopenia measure, okay, was quite significantly improved from from these individuals. And so we saw pretty significant mobility and cognition. This wasn’t even the purpose of the trial. We were just doing dose dose finding, and we’d looked at biochemical markers of catalase and Mel nyata, and so on. And so, this was pretty shocking. And we’ll be doing follow up on MRI type work going forward. So it’s clearly working and we now have lots and lots of people on it my mom, my my own family, and it really does work. People are getting better. It’s crazy. Because we’re so we’re so used to being told nothing works. And so if we take a look at this, their cognition was statistically significant even in a 22 patient population. And it said Stan was quite significant improvement in Sistan rates across using a chi square test. Now, plasma halogens have this vital ether bond in them and that’s what makes them so unique, but it also makes their dietary consumption virtually non existent. This violates your bond is designed like a fuse. It’s designed to be to be initially attacked prior to and it protects other nutrients. of your of your cells in your body. And so what happens now, what we found was if we took that people Melynda holiday levels, first of all, they all decreased over time with the drug treat with the treatment. But what’s more important is that people that are pre existing mental health levels, completely normalized them very strong correlation with decreased oxidative stress markers, which is what plasma antigens do. So we reduced oxidized stress and Cavalese increased. So we’re able to those individuals had baseline catalase levels that were very, very low. Okay, we’re completely normalized within a few months. And so catalase is one of those enzymes that are used for breaking for neutralizing hydrogen peroxide. And it’s a decorative enzyme so it has a protein so if it’s overused, it becomes degraded. superoxide dismutase is an interesting molecule because it’s both degradable, but it’s also inducible. So both low levels and high levels can be considered adverse. And again, we was less of an effect from Super oxide dismutase, but it still was there. So, C reactive protein and I have only my own personal experience on on C reactive protein being reduced after taking the Omega three plasma halogens. Other 20 supersystem participants, four of them had baseline CRPS over one. All four were actually had low baseline plasma halogens at the start of the trial, all four of them, CRP decreased by at least half a unit. And then half of them was less than point five by the end of the trial. So it’s doing what it’s supposed to do. So we this glycerol is effective at elevating the plasma halogens. And it’s doing something right. It’s reducing the oxidative stress though clearly, we can’t You can’t guess with melon dialdehyde and catalase levels, but we’re also seeing this this cognitive performance. So the question becomes, why, how does this stuff work? And why would it work? Why would you even assume we would work and this is where we’re trying to get into the biochemical mechanisms of cognition and neuro pathology come in. And the bottom line is it’s the reduced function is a cause and neuropathology is neuro pathology is not causing a reduced reduction in function is the other way around. We have a lot of this stuff backwards.
35:17
And this is where I get into the obvious versus not obvious, and the assumptions versus truth. Because if you think the obvious the obvious thing is that the earth is flat, like anyone gets up in the morning, you can see the sun rises in the east and sets in the west. Like you got to be a complete idiot to tell me that the Earth is round the earth is clearly flat. I can put a I can put a ruler out there and for the in statistically speaking, the earth is flat. It’s only under really, really great distances that it turns into having a curvature. This is the obvious answer. This you know, if you haven’t been taught this in school, this is crazy. Really, we’re circling around the sun and we’re spinning on an axis and our moon is like this is that it’s, it’s not an obvious answer. It’s only true, because we studied it significantly enough. And science has shown us that we have to believe this the actual reality and not what appears to be the same thing is happening. Here. Okay, the observations in Alzheimer’s and aging are clear. Hey, the brain shrinks. Okay, that’s not up for question. Okay, we get these, we get these neurofibrillary tangles on the inside of the neurons, and we get these amyloid plaques forming between neurons. Okay, these aren’t fake. These are real things that happen in the brain. The question is, why and when and how, okay, are these clear, unambiguous pathologies? Are they actually causing the functional deficits that we see in aging or is this an association that we’re just taking for granted? So, the obvious thing is if you have this healthy neuron, we get neurofibrillary tangles formed on the inside. We get amyloid plaques formed on the outside. And the assumption is that these neurofibrillary tangles and amyloid plaques cause neurons to degenerate that these are actually toxic entities and the toxicity of these entities caused neurons to die. And then once neurons die, we lose the function that they were performing. But this is actually not true. We go back to Brax papers back in 1991. He showed no evidence of amyloid neurotoxicity in humans. The plaque like deposit showed considerable variable variations in shape and size most of the remain devoid, a pathologically changed agro philic nerve cells. Cell processes show neither distortions of the neuro fill, nor accumulation of glial cells. The nerve cells situated within the deposits appear virtually unchanged. And see also this amyloid deposits therefore should not be confused with neuritic plaques. So he’s saying here in pathologically examines and this is they did 2600 brain offs of autopsies. brach and brach done small amount of work. And then he goes on to say, and he was looking at the progression of neuro pathology and this were the BRAC scale comes in. There’s no evidence of causality between amyloid and neurofibrillary tangles. Okay. depositions of amyloid are among the first changes seen in the brain. Most of them do not correspond to neuritic plaques, neurotic, like size and shape, blah, blah, blah. The fact that accumulations of amyloid are frequently found in the context of non demented individuals in the absence of neurofibrillary tangles changes. The cell these case numbers has led to the assumption that depositions and amyloid precede the development of nerve further changes. It is therefore important to note that in quite a number of cases, one can also recognize a contrasting pattern with cortical nerve failure changes preceding the deposition of amyloid. So the amyloid deposits cannot be conserved, this is 1991. This is 31 years ago. And then if you go on now, if you take a look when people tried 2000 to 20 years ago, they tried to actually say, how many of these neurons that we lose in hippocampus are due to neurofibrillary tangles, and so the count of them all, and was able to find that the nearfield tangles accounted for only a small proportion of loss 8.1% So most of the neurons that were dying, were not dying, because in their further tangle formation. And this is the information we have and so then they they do animal models, right. Here’s an animal model where they created an animal model where the neurons accumulate excessive levels of neurofibrillary tangles. And they were doing this to prove the toxicity of neurofibrillary tangles, and what they found was the opposite. They found that sorry, this thing is
40:10
that unexpectedly neurofibrillary tangles, Berry neurons in the visual cortex appeared to be completely functionally intact, to be capable of integrating dendritic inputs, effectively encoding orientation and direction selectivity and to have stable baseline resting calcium. And when they when the brain, when we look at the longitudinal studies, we’re launching the cross sectional studies of aging. The formation of amyloid and the formation of tangles in the human brain occur in two different locations. They don’t actually even occur in the same place early on, later on. They’re everywhere. But if you take a look, the earliest formations of tangles occur in the hippocampal ca one region and the earliest formation of amyloid is in the neocortex. So the question becomes what’s going on here? So you’ll see that you have the way neurons connect with each other where an axon connects to a cell body. You have the nerve every tangles on the inside, talks on the outside. And this all stems way back from 1978. When we’re looking at the association’s plaque counts in the brain, okay, brains with higher levels of plaques showed that they had decreasing levels of choline acetyl transferase. Which is a biomarker of presynaptic acetylcholine terminals, and acetylcholine esterase, which is a biomarker of the synaptic cleft, but the glutamate markers or the the postsynaptic receptors were unchanged. And then this beautiful was composite totally increased. So this is 19. This this really would stem the whole cholinergic hypothesis of Alzheimer’s disease and dementia. But if you look independent, it’s still in the same paper. Just mental test scores correlated with cooling acetyl transferase activity, you get an equally strong association. And so, colon the cholinergic function is clearly associated with cognition. And that’s true, and that’s why the first drug ever invented on this was the death the nausea pill. Aricept worked. He doesn’t work forever, but it does clearly work short term. So Drachman did a mazing studying 70s I didn’t have my pleasure of meeting him few years ago before he died. And he said he’s he never really do the study again. So we did he took these university students, healthy volunteers, and he gave them scopolamine which is a muscarinic antagonist. So he blocked the activity of acetylcholine on the postsynaptic neuron. And by doing that, he was able to create short term memory loss and these 20 year olds, okay, just by blocking acetylcholine function and then what he did is he took the same group, he gave them the scopolamine. Then he also treated them with Faisal Sigmon, which is acetylcholine esterase inhibitor like AirSep and he was able to attenuate the memory loss, really good old fashioned science here, cause and effect and I love this paper, hardly anyone ever over it, but So, the point here is that the blockage of acetylcholine at the postsynaptic neuron creates dementia. Well, if you take a look at scopolamine, okay, and there’s other studies where they study other things, but here if you just treated animals cupola mean similar beta levels increase and you would also increases with scopolamine phosphorylated tau. And if you restore the postsynaptic acetylcholine function, the cow levels come back to normal, normal levels come back to normal. So clearly, the color nergic function of the neuron is associated with the tangle and amyloid formations. And if you take a look at the cupola mean, cholesterol levels increase and phospholipids decrease and so of course, plasma halogens are one of these phospholipids Okay, they’re in this positive category of decreasing. So this is where things get continually more interesting. So the biochemistry of cholinergic neuron dysfunction again, truth versus fiction. This is how your brain cells work. This is also how the neuromuscular junction works. In we release these acetylcholine neurotransmitters in a synaptic cleft, they act on the postsynaptic neuron and propagate a signal. And workmen did a huge number of studies. And then you kind of burnt out because he couldn’t figure out what was going on. If you supply enough phospho choline, these these are these are striatal slices. And you can this is the amount of acetylcholine being released by the neuro terminal as and this is the number of
45:15
electron of action potentials. And you’ll continue to basically forever almost pump out acetylcholine, but if you block the choline uptake inhibitor uptake proton called with hemoglobin three, it breaks it blocks the choline heif in the transporter. So if you mentioned back earlier with the post mortem studies, I showed you that the choline hyphenate transporter, low levels of it associated with increased dementia, so if you block it with a drug, you reduce acetylcholine release and if you do that long enough without feeding the brain choline, the fossil liquids start decreasing. It’s called Auto cannibalism is what he calls it. Okay, so the brain starts eating itself essentially, it if you can’t get enough choline to keep going, it will eat itself. You’ll eat it’ll eat its membrane to maintain its choline levels. And this eating of the membranes happens with phospho coins and phospho ethanolamine. And all these studies back here, they didn’t really they just kind of grouped the plasma halogens in with the with the other phospholipids. And so what he showed very clearly and he published his paper in Science back then the reduced if you block the uptake of choline, you cause neurons to shrink and die. And this is where the next part comes in is the methyl transferase system and homocysteine. So it turns out when you’re making phospho choline not just in the periphery, but in your brain, one of the main mechanisms of making it is called and foster tell ethanolamine and methyl transferase. And the synaptosomes have one of the highest activities. So this methyl transferase activity is very very active in the brain, especially in your synapses. And so Kennedy did a wonderful paper where he took the post mortem studies of brains and he looked at sh so sad gnosall homocysteine so you guys, follow homocysteine for inflammation? Autism, you’re studying autism. This stuff? The methyl transferase system comes up all the time. But the brains of Alzheimer’s patients had high levels of sch and the sch causing inhibition of methyl transferase. Okay, this is critical methyl transferase I can’t see my slide very well here. And in fact, if he took the extracts of brains of an Alzheimer’s patient and ex vivo looked at whether or not they could inhibit catechol o methyltransferase activity they did and pemt. So the actual brain extracts of an Alzheimer’s patient is such that it is inhibitory to methyl transferase activity seal MP catechol o methyltransferase. And the FOSS title ethanolamine and methyl transferase. Well, that’s what’s going on right here. So this is where sh is being created is being created at the synapse terminals here. What happens with phosphorylated tau? What’s the relationship between the formation of phosphorylated tau and sch and FCM? Well as sch levels go up, you get a dose dependent increase in phosphorylated tau in exactly the same location of the human brain, where we see these things, which leads us to the homocysteine system, right so we measure homocysteine is a very powerful biomarker of dementia. Risk for other and also other risk factors. But homocysteine is really a biomarker of sch levels and based upon the percentage of homocysteine, okay, as you get older, the number of people that have high homocysteine levels okay when we’re in the early 60s with 25% of the population, but as we get older, the number of people that have high levels of homocysteine goes up dramatically. Less so now because our vitamin usage is getting better and better at this in the general population. But the cumulative incidence of dementia in subjects with high homocysteine is a highly highly reproducible observation. So homocysteine is strongly associated with cognitive impairment.
49:37
And this is where 20 years later, Ferguson Brickley kind of cracked the code that Wortman was working on way back in the late 70s and early 80s. And what he found they found was that this cooling high affinity transporter wasn’t actually on the postsynaptic or the presynaptic. membrane. It was actually on the vesicles. So unlike a dopamine transporter or a serotonin transporter that stick around all the time sitting here, the cholinergic neuron, the transporter that that brings the choline back up, isn’t actually on the membrane. It’s on the presynaptic vesicles, which means they don’t get expressed only during the fusion and the synaptic release of neurotransmitters during this process, so this membrane fusion process is which gives us all of our neurological function and not just in the brain, that neuromuscular function, our heart synaptic or sinus rhythms of our heart are all based upon this basic physiological structure composition of this construct of membrane fusion. Turns out membrane fusion is entirely dependent on plasminogen levels in the membrane. So we want to look at 100% plasma halogens of the ethanolamine pool versus 25%. Okay, so 175 5025 So as the plasminogen level in the membrane goes down, the ability for membranes to fuse and releasing neurotransmitters goes down with it, which is why this association is so strong that we see in human postmortem brain samples. This association here is is basically measuring the level of plasma halogens in those synapses. And of course, scientists have been studying this for a while now they’ve looked at what happens if you if you have an animal model that is plasminogen deficient from birth. Well, it needs or limit animal has equally decreased abilities of acetylcholine and glutamate release. Okay, so if animals are born and grow with with low levels of plasma halogens in their brain, they have impaired neurotransmitter release both the endogenous and the radiolabeled versions and their brains shrink. Okay, the white matter, okay, levels are dramatically reduced. And this is what we see in inborn errors of metabolism of plasminogen deficiency. This is also we’ve seen premature birth, and it’s also mildly seen in the difference between breastfed and formula fed babies. And so, white matter this is myelin, basic protein levels dramatically decreased. In animals that can’t make plasma halogens and their brainwaves are way down. And they’re myelination, the, the, the speed, the conduction speed of their neurons and their myelinated neurons are dramatically reduced. And of course, that’s firstly everything that’s our that’s our Schwann cell. Nerve conductivity as well as our as our oligodendrocyte brain cells. So this is what plasma cells looks like in the in the adult population. Now, this is where 18 One version, this is oleic acid. This is the one that’s in our myelin DHA version, that’s the one that’s in our synapses. And you can see we peak in our 50s Typically, and then we see this systematic decline. And this has been reported since the 60s. This is not a brand new finding we just did this is a bigger study with about 1000 people that we published on and this is brain volume decline with age and this is how the human brain declines. With age. It’s a pretty scary number. You can see we basically stay fairly stable to our mid 50s and our brains start shrinking. And if we look at plasminogen restoration, if we take plasminogen and restore and we take cholesterol, those cells with cholesterol, cholesterol will increase amyloid formation can go ingredie to plasma halogens, we get a dose dependent decrease in amyloid formation in cell culture, and we get this dose dependent increase in alpha secretase levels. What we see in the laboratory is what we see in human brains. This is human post mortem brain samples looking at the levels of amyloid in the brain of individuals high levels of plasma emotions, versus individuals with low levels of personalities in the plasminogen is actually will counteract the neutralize equally for genotype.
54:25
I won’t get to detail here that the eight the ATP Alpha soluble APB Alpha. Obviously people are excited about amyloid for years. But we cannot actually create an animal model we’re amyloid precursor protein has mutated because they all die in utero. And the reason for it is this soluble ATP alpha is a very very potent neurogenic factor and people are now seeing it as a treatment neurogenic treatment in and of itself. So the final thing I want to talk about, is this brain shrinkage. Does Alzheimer’s actually cause brain shrinkage or is it the other way around? And I found this study very, very interesting. So they did this is they did pathological diagnosis. There’s two tables here, pathological diagnosis and 626 pages with clinical diagnosis of ad. So all 626 of these people had cognitive impairment. And then they in a blinded way, the pathologist looked at the brains that how many of these clinically demented individuals do we have pathology and you’ll see that the brain weights are pretty consistent across all of these, the only thing different is the that had a pathological diagnosis normal was slightly higher, not nothing significant. But they’re all right around 1000. You know, a kilo. What happens when you do the study the opposite way? What happens if you do a clinical diagnosis of 227 patients with a pathological diagnosis of purity? Well, now you see the correlation with brain size. So here, remember all of these have a pathological diagnosis of Alzheimer’s. But if you have a pathological diagnosis of Alzheimer’s and you’re cognitively normal, your brain is still have a normal weight. So, the biochemistry of impaired cholinergic neurons, the impaired cholinergic function results in the following reduce false and if it’s a we get shrinkage, increased total cholesterol phospholipid membrane ratios reduced alpha secretase, increased amyloid precursor protein, and so on. Increased phosphorylated tau, reduced mitochondrial function, increased oxidative stress. So maintaining acetylcholine neuron transmission, the crec salies. So it’s a functional we lose function and as a result of that loss of function a lot of these other bad things happen. So, maintaining acetylcholine function is really what it’s all about. Cognition is correlated with and dependent upon sustainable presynaptic acetylcholine neurotransmitter release period. It’s over and over and over again shown that the reduced synaptic choline uptake via the coin high affinity transporter, that’s the Achilles heel of the cholinergic neuron. And it’s the root cause of cognitive nerve regeneration in Alzheimer’s and an aging and it’s the root causes sarcopenia. The choline high affinity transport is localized on presynaptic acetylcholine vesicles. And is only expressed on the presynaptic membrane following depolarization and fusion. So anything that anything that inhibits membrane fusion and neurotransmitter release, will inhibit this uptake and will cause a degeneration cascade. So a membrane plasma halogens are depleted and Alzheimers and an aging. So when we look at this as a drain health perspective, okay, obviously these plasma halogens we can try to get more of them through resistance training, intermittent fasting, those things help, obviously reducing toxic load in our bodies will help but it’s pretty hard to get enough so plasminogen supplementation is going to become more and more normal. It’s kind of like breastfeeding for adults. Okay, it’s pretty well what it is we’re saying these critical nutrients we don’t stop needing them later on in life. The other thing that I noticed a lot in our practice and patients or doctors is possible choline levels get decreased. It’s hard to keep up on those. So let the sin is important. The methyl transferase reserve a lot of this issue with creatinine or creatine for muscle wasting, is involved in methyl transferase didn’t get into detail but creatine and choline are the two main drivers of homocysteine levels. You want to make sure you got b 12, B six methyl folate, mitochondrial capacity and so on. But that’s kind of in a very rapid fire process kind of a real short story of the of the plasma halogens and and
59:13
so on, so Okay, I will, we can talk. We can fire away the oh so the Maokong impairment. Yeah, so I’ve had dramatic my aunt, for example, she looks so bad and long term care. And it’s hard when people get into long term care because they locked them up and you can’t get into them and help them. But she was at the point she couldn’t recognize my cousin’s any longer. I have her unfortunate formulas of neural she can now recite everybody in her 50s wedding anniversary lol. Okay, these are real events that are occurring in people’s lives. And so, mild cognitive impairment brain fog COVID is interesting. COVID specifically reduces the Omega nine plasma allergens in the lung. Okay, this is documented and published, that it affects lung function. And we’ve had several people pull people out of ICU units on lung function by giving them the glia Omega nine. And anecdotally like from our doctors out there, the brain fog and energy, the neural seems to help for sleep and for the inflammatory component. The glia seems to be more important. glia is really the concussion stroke. You know, TBI, autism type molecule, and neuro was more for performance. How long does he plasminogen depends on the dose. Typically, within a few weeks, you start seeing things and you start seeing usually people see better eye contact. They’re more engaging with each other. And then it kind of slowly built up from there. When do you use Glee or neural? I’ve, I’ve changing as time goes on. Typically neurone personally, I take neuro in the morning. It gets me through my morning fast and everything else like so I take a couple grams a couple mils of that in the morning and then I take glia but an hour before bedtime. And so I use Glee at night for white matter restoration. And I use neuro during the day for performance enhancement. It just wakes you up. It is kind of it’s weird. Neuro kind of makes your brain do this. It feels like you open up okay and glia feels like you put glasses on your brain it kind of makes you feel like this. And so, depends like people with autism or ADHD during the day. Neuro can make them more hyper. And so you learn a little bit careful that briglia really puts on focus glia I’ve got some pretty interesting results with glia in bipolar disorder, by the way as well. What happens with the vestibular nerve or neuritis? It’s a good question. Typically anything that’s inflammatory I like to focus on restoring and rebuilding first. The best way to think of Glee and neural is like tuning a radio station. Okay when the radio station is out of tune, it staticky. Right and that’s that’s because the impulse the axonal impulse is being scattered. It’s not being clean. And clear going through the your transmission is scattered is losing it. And so if the volume is low, you can still kind of get signal but if you crank the volume up all you hear static, so glia is about making that neurological signal clean. Neuro is about turning the volume up. So typically when you have an inflammatory or neuropathic pain, where you have some sort of neural inflammation, you want to work with glia you want to work with mitochondrial support like and acetylcysteine carnitine phospho choline, you want to get that make sure they get their cholesterol levels up. If they’re, you know, trying to get their cholesterol is in the mid to hundreds. Try to get that membrane structure back. And then after that, you can turn the volume
1:03:09
dosing you know, I’ve been conservative, and we’ve changed that more and more. I like to step people up. If you’re just looking at for your own longevity and health promotion, a couple meals a day is fine. Like, you know, the gel cast before gel caps is kind of what for people over 50 For example, if you’re if you’re trying to turn back the clock, if you’re trying to rebuild membranes and rebuild the brain, then you have to get up to more of a four mil per day dose. So in the clinical trial, you can see the two mil goes it up there for a while, but we really started seeing effects in cognitively impaired persons when you get to the higher dosage. So it is you kind of find it yourself. You can kind of you can go to a loading dose and then bring it back down again. And that’s what I’ve learned over the last little while is that you know what, let’s get this dose up. Let’s get people seeing an effect. Then bring it back down again and if they can, and then the I find that the patients are more powerfully motivated by Oh, I had function now it’s kind of going away. Otherwise, it’s this delayed gratification sometimes if you take too long to get an effect. But that’s, I think people have their own you know, each person is going to be different. neuron glia. They’re called proto neural. It’s 100% Omega nine Omega three, it’s a we get the DHA from an LJ source and then we attached the Omega three DHA onto the plasminogen backbone. And it’s you can take it in the fasting state. The nice thing about these precursors is that they they piggyback on your triglyceride pathways of the body, and this is what feeds your brain when you first eat a meal. The very first thing when you eat a meal is that your triglycerides go through your VLDL system and you’ve V LDL system is designed to feed your brain and your muscles first before anything else in your body. And so that’s the first source of food energy that you get after a meal and that plasma halogens backbone, the the Oculus rails piggyback on that system, which is basically what breastfeeding is basically it’s what it is how it how it piggybacks on their caps betting the liquid or the other way around. It’s proof I guarantee you you will hate the neuro taste it’s it’s it’s nasty stuff. So the the gel caps are what people want for the neuro. The Omega three version I still take the liquid version because I’ve gotten used to it over the years. But and glia it doesn’t really matter. That’s whatever’s convenient for you. Ugly it has no problems for taste like for for children that are on feeding tubes and so on so forth. Obviously we have a liquid formulation, but the glia you can just trip it into your food. It’s It sounds simple, silly, but that’s pretty well as simple as that. mentioned, is there any evidence that fasting can increase plasminogen levels? Yeah. So the your fasting state is where anything that improves proximal function, okay, so anything that you would normally do to lower triglycerides, for example, in a high triglyceride person, so if intermittent fasting or ketogenic diet, resistance training, all of that will improve proximal function and when you improve proximal function you will improve plasmatic levels. Okay, so that’s the simplest way and then you have resistance training and intermittent fasting is probably the best natural source of doing it.
1:06:50
Our plasmatron source from shellfish No, this is all vegan based. And it’s also not just because, like I’m not really, you know, some people are vegan, but it’s mostly for cleanliness and clarity that we take a triglyceride source that can we use an algae source for triglycerides, and then we saponify it so and we digest it off to get the free fatty acids and then we purify those free fatty acids. And then we take those pure, free fatty acids and we put them on a plasminogen backbone. So this is a pure chemical synthesis using natural sources so that the product at the end is completely free of any trace metals. It’s the purification is very, very good. And so that way, it’s not from shell, and that’s also it’s important that we get the structural specificity, right? It’s when you take a DHA plasminogen you want the DHA plasminogen to go into your synapses, okay, that’s where you get the immediate impact over 12 to 24 hours, they kind of spread out. But for that, for that short for the first phase, you want that precursor right and Omega nine, the glia as 100% Omega nine and that that fatty acid comes from a sunflower oil source. So the source of the fatty acid is just convenience and and cleanliness. But we it’s fully processed and purified in our system. So when you want to focus on the white matter, you go with the glia Yeah, so fenofibrate Yeah, probably. I don’t have direct evidence, but I would, I would predict that fib rates will increase plasminogen levels they do in cell culture and other studies. For sure. And some cancer is a very interesting story. So it’s as it’s a more complicated one, but plasma origins are deficient in virtually all cancers. Okay, colon, pancreatic, breast, lung, ovarian, I’ve studied only firstly, every cancer and there’s a pre existing low level of plasma halogens and that’s linked to this impaired fasting state in all cancers. But in taking plasmids, like the old molecule, thistles, one of the really good usages were in the 70s. Even from shark liver oil, for example, was reduction of toxicity from radiation therapies. So they do reduce tumor load. I would be cautious in a metastatic patient. So for prints of prevention and for early cancer treatment, metastatic cancer, I think you’d want to be a little more careful because when you have an actively growing cell system, okay, you’re they consume plasma halogens and there’s not a huge amount of data on this. The data that is out there indicates that plasminogen supplementation RealFeel glycerol shrink tumor volumes and tumor growth rates. But those are small studies. So I think patients should keep an eye on it. The close whether statins, inhibit plasma halogens, actually probably the other way around the trophic effects of statins. JustAnswer Funny thing is stats are a little bit of poison and then your body’s reaction to the poison gives you a bit of a benefit. Okay, so what stands do they’re basically a mitochondrial toxin, if you will, they block HMG Co A and so they they block your cells about ability to make cholesterol. And the compensation mechanism for that can have increased plasma allergen levels so you get this lowering of LDL but sometimes you get this increase in HDL and the increase in HDL is due to improve proximal function sometimes. So I’m not a big statin fan. I think they’re mostly a waste of time. But they do have some of that your body will react to it and your reaction to the statins creates a positive outcome. Well, there was another one that we are he flower oil. I don’t know much about that. Whoever asked that question. Can you tell me a bit what he flower is? Oil okay, we’ll get back to that. If you asked. Fine.
Bill Clearfield 1:11:10
Fine. Sorry. It was Dr. Fish by Nance that so I don’t know.
1:11:15
He’s backing on the flower oil. Yeah. Yeah, I’m not familiar with that. High Dose vitamin v one. The B vitamins I think is an interesting one. Of course, we forget about b one b two and B three is like, like niacin is something we should be on quite a bit. And supplemental doses of plus of B vitamins are important because there’s a pharmacokinetic pulse. It’s not. So it’s not clinically equivalent. Like if I take if I spread out a B vitamin dosage during my meal and it gets a slow spread. It’s not the same as getting a pulse that gets into your cells. So yes, so fireman, B to for people that are trying to get their their their trace metals up. Like for zinc and copper and iron absorption, beaten riboflavin deficiencies are another some of these B vitamin deficiencies are extremely underreported. So I’m a big believer in relatively high dose B vitamins with little holidays. You can take them for a day or two, take them off day to get I’d rather people take a slightly higher dose for a shorter period of time and then take a holiday than just take a low dose chronically because you you kind of want to get these things into the cells, your cells, everybody actually a little trapping mechanism. Right? So if you if you pick them, they’ll drive them into your cells and your cells. will hold them. Okay and it’ll dissipate out afterwards. But sometimes if you just get low levels, just your main cells get get the vitamins not all your cells get your vitamins. Can you OD on plasma halogens I haven’t found anything it just turns into food energy turns into very very expensive olive oil, basically, and very, very expensive fish oil at some point in time. But yeah, you can od in anything I think. But technically speaking No, it just turns into your body will just consume it as a calorie source at a certain point in time. It’s it’s it’s basically food or feed it flowers derived from corn Gramma plant flowering plant that English stays mainly funded by the rich in essential Omega three alpha linoleic acid, okay, and stearidonic acid, so alpha little linic so the Omega three like olive oil, or flax oil is also their powerful body doesn’t use very much of it. This is an interesting thing when you talk about your omega threes. People talk about the alpha linolenic acid and EPA for example is another one. But really all of these are just big players. DHA is what your body wants. And if you look at your body, like alpha linolenic acid is a key part agonist so it’ll stimulate proximal function. So fatty acids themselves are bioactive molecules. They are they’re both nutritionally they’re used actually as building blocks but they’re also signaling molecules. So when you take an alpha linolenic acid from flax, or from or you take EPA, for example, those are P par agonists. And that’s what gives them their triglyceride lowering activities, but your body doesn’t use them. If I take your brain or take your muscles and I measure how much of your membranes contain alpha linolenic acid, it’s almost undetectable. It’s way less than 2%. And same thing with EPA, like your body uses very EPA as a metabolic byproduct of DHA. And so your body doesn’t actually use it and when you use it as a drug, whether using it for Is it using it to replace arachidonic acid levels? And so it’s um you know, like, that’s why all these these food is medicine right? These supplements like they’ll have some of them will be biochemical intermediates, but they also have signaling powers. They will actually the the they’ll do some things other than just just nutritional aspect of it. So our Ks two inhibitors like Repatha I apologize for my ignorance. What do those do? RS K, RK s two
1:15:16
and I’m not familiar with those apologize.
Bill Clearfield 1:15:21
Dr. Richwine Do
1:15:22
you have ever
Bill Clearfield 1:15:24
that is RK s two inhibitors like Repatha? Well that’s they use that for cholesterol lowering has an adjunct to statins.
1:15:36
Yeah, see, the optimal cholesterol levels in humans are between 220 and 240. For longevity. Soon as cholesterol gets under 200, you’re all cause mortality doubles. When it gets down to 150. You’re three to four times the average death rate of the average person. So longevity, you don’t want to get your cholesterol under 200. Soon as cholesterol gets under 200. I’d like to see cholesterol over to between 220 and 240. Ideally, LDL should be over C 120 to 140. And you want to keep your HDL levels in that 60 to you know, over 50 For sure, but definitely ideally 6080 range but yeah, so and this is not trivial. These these are millions of patients, multiple country wide studies, looking at all cause mortality. And the as you get older, it’s more and more important that you don’t become cholesterol deficient. Okay? If so, for longevity, it’s, it’s really not. It’s in contrast, it’s the data is very, very robust on this thing. So yeah, so lowering cholesterol is something that the only value it has is if you have lots of oxidase, oxidized LDL. So Statins have a clinical benefit in people that have a pre existing high CRP level. Okay, and so what you’re doing is you’re way lowering overall cluster levels, you are also lowering the risk of having oxidized cholesterol, creating an atherosclerotic cascade. But if you have if you have low CRP, your cholesterol is pretty well benign. There’s nothing toxic about it.
Bill Clearfield 1:17:10
What’s your definition of a low CRP or a high CRP?
1:17:15
I like to keep our CRP under one, ideally, but try to keep it under it when it gets over. It shouldn’t be, it should be under one and if you target it, you should be able to get it down there. But if you have inflammatory like you guys are, you know, dealing with these people who have chronic inflammatory issues, but the real danger comes in and get something that three to five and higher. If it’s chronically above, you know, that level but
Bill Clearfield 1:17:42
do you see any danger when it goes say from 0.8? To we do it in our practice regularly, at least every six you’re always first and least every six months? When it climbs like from like 0.8 to 1.2. I mean, that’s technically normal.
1:17:57
It can happen like I’ll give you an example just I was doing some work. So you have to be careful how people are working out. Like when’s the last time they’ve worked out before getting a CRP test done because exercising will increase your CRP levels and takes 48 hours from an exercise routine for your CRP to normalize and based upon your your basic oxidative stress situation. So for example, just three weeks ago, I was we were doing this little mini trial with people here. And so my CRP was 2.5. Okay, because I had worked out and I wasn’t paying attention, right? I took kind of a third of a bottle of neuro and the very next day it was point 824 hours. So CRP can change like it’s a good general marker of inflammation. So especially when when you see CRP high and homocysteine high at the same time, I like to use CRP in context of other inflammatory markers. To see are we truly getting a generalized situation? Or, Yes, I always measure CRP, I think it’s important marker but just recognize that it can be somewhat dynamic in terms of its levels, so yeah, so I wouldn’t unless unless you see a reason for it. And if it if it climbs and it’s chronic, and you can’t, if you just can’t knock it down with anything, then you just, I find it really useful to to as a endpoint to tell me am I am I finding the right buttons to push? Right? Because theoretically, like there’s, it’s it should be you should be able to drop it down. Our, our cast members are not statin drugs, different mechanisms, so I’m not sure how it works. Cholesterol transport, you want cholesterol, reverse cholesterol transport working properly. Your body your cholesterol, remember, it’s not your cholesterol levels is cholesterol in your membranes. And it’s like it’s like your temperature switch on your wall. Your membranes were designed to a certain level, and you need to be able to export it through the HDL system, and you’ll be able to bring it in through the LDL and make it internally and those two mechanisms regulate your cholesterol levels. And usually the biggest problem that we have with aging and disease is that the HDL system starts getting impaired people become choline deficient. And when you’re you have low levels of phosphate choline. You can’t your your cholesterol export mechanisms, like if you want to get the foamy macrophages down, it’s cholesterol export, which is why the phospho choline IV therapies like when, when you like, when you give people IV phospho choline what that does is it sucks cholesterol to cells through the shell system. It dry, it drives the HDL reverse cholesterol transport system, because HDL requires fossil coin to work. So that’s really kind of what you want to, you know, that’s a bigger conversation. But
1:20:54
anyways, that’s going
1:20:55
to be a plasma which is one of these weird things that you can’t unsee them. The numbers are just so damn big. And, and they’ve been sitting there in plain sight for years. We’re talking about 30% of your brain. Like your your heart, your lungs, like the second highest concentration of plasminogen in the human body is, is the human heart. It’s just ridiculous. Like the levels of these things we have, like we’re not talking about micrograms, we’re talking. These are pounds of this stuff in your body. It’s just ridiculous that it’s just not even on our radar. You can go to like it’s on Amazon and it’s on proton.com you can get out there and then the blood testing. We have blood testing, we do certification training. We do similar things that you’re doing right now, but we do case study, study, you know, people as people get involved in research and my goal is to bring some of this research level testing and technology into everyday practice. So that’s not such a like if there’s such a gap between this type of research and the implementation. It’s not a lack of knowledge that we actually know a lot. We’re just really bad at in implementing the knowledge that we have and so it’s it’s kind of, for me personally, just saying, You know what, this, roll our sleeves up here and start applying some of this knowledge and the barriers and the time windows to get these things into place. It’s just It’s just ridiculous like cholesterol, like I just got my friend like my person with bipolar that we’re taking care of. Blood tests into LabCorp comes back. The dietician just called me today. Well, he was closer all the two away, we should you know, we it’s Hi, I’m gone. You know, and you have to be polite. But that’s just not true. And so, if we can’t deal with these kinds of simple systems, that’s kind of what we’re dealing with. So, you know, we’ll get there you know, try to help one person at a time as best we can. So,
Bill Clearfield 1:23:02
so how do I explain to my to our resident lipid ologists, Dr. Lillo who’s, you know, all over the cholesterol should be basically zero and there’s no convincing them otherwise. Okay. Well,
1:23:17
if you guys have 10 seconds, I will pop up a presentation I slide for you guys. And this is this is the slide to make people like that. Go away. Like in a polite way
1:23:39
okay you guys we share you guys will see that.
1:23:57
Yes, this is like one status 2019 12 point 8 million cohort subject. This is hazard ratio for total cholesterol, men and women. Okay? all cause mortality. And if you go by age, okay, so as cholesterol gets under 200 Here, especially when he drops here, this is where you’re all cause mortality creeps up. And as you go from if you’re 40 to 55 years old. Here’s your all cause mortality risk of high cholesterol like look at this this is all flat from 200 to 260. A total flatline here for all cause mortality risk. It doesn’t start going up until you get below 200. Okay, and this and I have populations like theirs and as we get older, you’ll notice that we’re getting this population segregation, we’re starting to all these people low cholesterol starting to die. Okay, this is what you’re seeing here. You’re seeing this, this population preservation going on. And so these these high cluster people keep on dying off. So by the time you get to 75 to 99, like you’re down to this flatline, but if you can see it’s totally flatlined. And I can go through all the statin I go this is actually on my website if you want to go through the cholesterol presentation and you can hear me talk about it in different ways. But yeah, like how do you how how do you treat someone
1:25:34
when you have this kind of data?
1:25:39
Like I don’t like how do you say well, this is bad. We you know, 200 is bad. We got to get you down here. Well, it doesn’t look like it’s smart to me. And so that’s kind of and you can go through there’s much much more. There’s this is only one of several several studies looking at this. And yeah, so you can kind of go through that kind of stuff. And the HDL levels, and so on. So that’s kind of so when you talk about statins and even the statin therapy, we look at cancer and mortality with statin versus non statins. So I explained that data, they do some trickery with statistics. But I got a presentation on cholesterol and there’s another one on cancer to help cause cancer fundamentally is driven by cholesterol dynamics as a general rule, and cholesterol clearance capabilities. And that’s why that cancer cell shifts to a mitochondrial system. Some things
Bill Clearfield 1:26:37
well, we definitely definitely asked you to come back for to give us a more on that a little bit down the road. So I think
1:26:45
I love this stuff. This is what I live for.
1:26:48
I haven’t I have this question. And so cholesterol is being carried by low density lipoproteins, right. Yep. Okay. And most of the time, they don’t relate the death to the cholesterol per se. Cholesterol per se does not cause any harm to the blood vessels. But the oxidized form of LDL.
1:27:16
Yeah, so oxidized LDL atherogenic. But this is the important part. So people think we get this mindset of the molecule as a toxic protagonist. It’s actually doing something. Okay, homocysteine is toxic to Mao is toxic. That’s not true. These are biomarkers. Okay, TMA. Oh, okay. If I inject that into you, it actually prevents heart attacks. Okay. It’s a measure of gut dysbiosis. Okay, which is correlated with cardiovascular endpoints, but TMA itself has no toxicity to the heart. So but cholesterol is an important part. Think about it because you have two main systems, the LDL, three systems, the LDL system that transports cholesterol, and it gets LDL gets absorbed into the cell through the LDL receptors, and it gets digested in the lysosome. So your cells actually suck LDL and that’s how cells get cholesterol if they need it. Okay? And HDL is what the excess cholesterol in the cell. When it gets sent outward. It gets recirculated and it gets shared among the cell. That’s why it’s so important in the brain that your HDL system can share cholesterol, but your cells take up cholesterol only when they have to. Okay, so what statins do is they prevent the cell from making their own cluster all and they force the cell to cholesterol from the blood supply. And so it stands to the upregulate the LDL receptor, so they forced the cells to consensus they prevent the cell from making their own cholesterol they forced to sell to pull cholesterol from the circulating system, and therefore you lower LDL levels. And so, the when you have good internal cholesterol metabolism, the cells don’t need any cholesterol. So you know what I’m fine is like it’s like having a it’s like having solar panels on your house. Okay, it’s like you’re actually donating energy back to the system. And that’s where the that’s why LDL system and that’s why low cholesterol becomes quite a negative health consequence because it indicates that the cellular health the person is impaired, and indicates the cells of the body are having a hard time making enough cholesterol. There’s something wrong internally in that cell, because if it can’t make its own cholesterol, it’s forcing it to get its cluster from the blood supply system and the LDL system, and that’s why that’s why that negative that high mortality goes up with low cholesterol. There’s another
1:29:39
version of the story is that the cholesterol LDL, even if it’s high, is not the cause of damaging the blood vessels, but the oxidized form of LDL, where it become free radical generators, and they start eating the blood vessels by oxidizing them and that generate the plagues. So when we looked at the risk of cardiovascular diseases, we see oxidized LDL as a factor, not the level of LDL, even if it’s high, it’s not necessary that it’s going to cause high risk of having cardiovascular oxidized LDL it is and then oxidized LDL is a factor of other things, which is the oxidative stress of the of the patient so in generally, let’s say if patients has high glucose, and non controllable, then those of glucose will be oxidized and become glycans. And those glycans oxidize glucose can oxidize LDL and become oxidized LDL. And so here the problem here is really not all the way affects it. It just lowered the sugar by and preventing those sugar from reacting with those free radicals out there. And the other way of doing it is also giving antioxidants and clear those those free radicals because that’s the factor that leads to oxidized LDL, right?
1:31:15
Absolutely. That’s all correct. And what happens with the oxidized LDL is it gets into the endothelial dysfunction, it gets in it gets into that endothelial layer of your arteries and then it can’t get out. Okay? And then we’re filming macrophage,
1:31:31
right? They are free radical generators, they just damage and eat and oxidize the blood vessels, protein components and lead to the endothelial dysfunction. But the way you manage it is actually buffering the redox. Now that we’re giving antioxidants to neutralize those free radicals that leads to the oxidation of LDL or lowering the sugar because the sugar can be also ice high off it can can oxidize, like when
1:32:07
sugar levels increase your insulin, you become insulin insensitive, it means that your cells have a problem metabolizing sugar. So if your cells can’t metabolize glucose and saying hey, I’m full, stop sending me more glucose. I can’t, I can’t metabolize the glucose you’re already sending me and so it’s not pulling glucose into the cells because it can’t it’s saying, I’m too I can’t process the glucose that you’re already sending me. Then glucose levels increase, which then causes insulin to go up. You’re saying, Well, what’s worse, I’m going to force this glucose into your cell because if you don’t take care of it, someone else is gonna take care of it in my body. Okay, I’m gonna get fatty liver or something else with it. And so yeah, so improving the and that’s why intermittent fasting and exercise lowers, lowers cures type two diabetes, because what you’ve done is you’ve increased the cellular capacity, the glycolytic capacity of the cells and as soon as you get that cellular energy back, and the cells can now process their normal levels of glucose, all of a sudden glucose levels go down and your your need for insulin goes down and you’re no longer insulin insensitive anymore.
1:33:15
Right. And the other thing is that when you give them insulin, really even the high sugar is not the real real cause of the oxidation. It’s the insulin itself and when you give insulin to lower the sugar, and you’re giving it all, you know, more frequently because of the diabetic. I think it’s more causing more even oxidative stress and more damaging to the blood vessel stenciling itself, because it uses free radicals part of the mechanism. It internalizes sugar, but it generates a lot of free radicals that will oxidize the glucose and so treatment of using insulin, right it actually with time, it makes blood vessels more worse. Because of the the byproducts of that adding insulin. It just generate free radicals correct and
1:34:12
when people have high glucose is it is it because they’re insulin deficient? Okay, like you’re not giving someone you’re not giving an insulin deficient person insulin to lower the glucose. They have they have normal insulin but that insulin they’re called insulin insensitive because the normal levels of insulin isn’t driving that glucose into the cells of the body. And so the question really becomes is why
1:34:36
right so what you’re doing is because of oxidative when. So this vicious circle docks, the free radicals and all that makes the internalization system not working, because it will oxidize those receptors and then suddenly become insensitive and sensitive, and they cannot get the sugar and the exact Oh, that’s what you wish I’m talking about. Which mean it’s really wrong for people who say, Oh, I’m going to eat chocolate and sugar and they take insulin.
1:35:09
I know I have
1:35:10
family friends do that to say, Oh, this is great. I can just I just give myself a little extra insulin after my meal. And you’re going Wow, man. But yeah, so I think the biggest thing we forget to do is ask the question why? Right? And, you know, why is my glucose high? Like what’s causing doesn’t and so sometimes we just kind of blindly, you know, forcing so yeah, so I agree with you on that one. And then that’s why that’s why the lifestyle interventions for type two diabetes have much better outcomes. Then insulin force some Yeah, so but yeah, it’s like, yeah, that’s the human body is is is a tricky animal. It’s got a lot of things that can can make you think that’s for sure.
1:35:59
So doctor, well, yeah. Are you there? Yes.
Bill Clearfield 1:36:01
I’m here. I’m
1:36:02
gonna steal the doctor.
Bill Clearfield 1:36:04
You can remember so you can always steal my folks as long as I can steal yours. So Dr. Lawson runs a parallel group tours on Monday nights, so Okay. Okay. So. So, Doctor good. No, we can’t thank you enough. This was fascinating. It’s something that you know, a lot of us you know, don’t know a whole lot about or, you know, sort of touched on in the periphery and we thank you so much for spending time with us. And for those of you that are new here, we’re here every Tuesday night, if, if you like what you hear we are in aos or d.org/webinars. We had over two years worth of content lectures that we’ve we’ve been doing for the last two years. This is the kind of content that the AOA doesn’t want that one out, you know, we were canceled as we mentioned when we started and what we’re going to return it persist. So we thank you so much for your time, and I’m going to twist your arm a little bit in a little while. To come back in a couple of months, and maybe elaborate a little bit more on the, you know, cholesterol levels and some of those things that you touched on, you know, a little bit a little bit deeper. Thanks. And again, we really, really appreciate it next week. We have Dr. Brian Evans, who’s actually from Reno Nevada like I am and he is an interventional and integrative radiologist so again, you know, things we don’t really hear too much about, and he’s doing some very, very innovative innovational procedures. And, and so will we’re anxious to hear from him. Dr. Monroe again, the link is aos rd U S. rd.org/webinars.
1:38:09
You’ll also get our
Bill Clearfield 1:38:11
our full conferences are on there also under slash conference or previous conferences, so. So anybody else who would ASR d.org/webinars Like I said, There’s well over two years worth of lecture material there. Some of them have a lot of them have narratives text with it. slideshows also. And anybody anybody who’s new, you know, please join us Dr. goodnow. Again, we can’t thank you enough. We will be here again next week, same time, same station 5pm, Pacific 8pm. Eastern, and if there’s anything new on the on the integrative medicine front, and the AOA, I’ll let you know. So far we’re surviving without them. But you know, we’re, we were a little bit the dearth when it comes to CME credit, accommodation. So just so you know, doctor know, we are ama we are the American Osteopathic society for rheumatic medicine. evatik diseases. We are ama ACC MV accredited, the AOA decertified us. Okay. So, I’m still having a hard time wrapping my head around that one. But that’s that. And, again, anybody who’s who’s interested in presenting you know, some material, these are not CME credits so, you can talk about your products you can talk about your, you know, your your, your, your, your research, we’re not restricted to generic issues, things like that. So, so and we’re always happy to, to hear from from everybody, anybody we can be getting a lot of attaboys kudos. You know, who’s thank yous one, Brad Zynga I think he’s part of your group states that the lecture stirred is glia. So I like that I might have to, I might, I might have to steal that one. It’s it’s pretty good.
1:40:23
So, again,
Bill Clearfield 1:40:27
thank you so much. Anybody else have any questions? We’ll let you go. I know it’s, I’m not sure where you are. Are you in California?
1:40:34
Yeah, I’m in Temecula, California, just so far from five hours. Reno is a little farther, isn’t it? Yeah. Reno.
Bill Clearfield 1:40:41
Reno is probably about eight hours. So but we get around and
1:40:46
Dallas? Yes. This is Dr. Patel and Dr. Dan also gives a very good lecture on autism and the use of these products and you may like to also include that for him in the future.
Bill Clearfield 1:41:03
Okay, well, we’re definitely going to bother him to come back because he’s got a lot of information that a lot of the things that I deal with so so and we’re always looking for the you know, you know, you know for the next thing we can add to our repertoire, and I got Brad’s genius as your Hannah Montana is neighbor. So I’m not sure what that means,
1:41:31
but I don’t know who that is.
Bill Clearfield 1:41:34
So I’m not sure if that wasn’t that some kid actress or
1:41:39
- Huntress maybe? Yeah, yeah. Miley Cyrus.
Bill Clearfield 1:41:45
Yeah. Yeah. And turned into something else. I think if there’s
1:41:53
okay, it used to be a kid and not our kid.
Bill Clearfield 1:41:57
Yeah, those things happen. So, that’s for sure. Okay, okay. All right. Um, so we’ll have the the video up. Usually it takes 24 to 48 hours to get it get ready and go. We’ll have it up on our website, and anybody again, anybody else? I gave you my email. Do CTR bi l nine@gmail.com. If you’re interested, we can add you to our mailing list. So let you know about all about our whatever programs we’re running. And Dr. Burgess you have anything for us?
1:42:36
No, just very thankful for Dr. Good now. That was great. Thank you.
Bill Clearfield 1:42:43
Okay. Dr. Hartman, anything from you?
1:42:47
No, no, I’m still finalizing my presentation. I’ll be giving on the 25th. myself my involvement in the prostate community trial.
Bill Clearfield 1:42:59
Yeah. All right. All right. So I’ll be anxious to hear that because unfortunately, I’m in that I’m in that the age cohort now. So do well. Doctor How about that kind of loss Have you got anything for us?
1:43:13
Well, I want to see you on Monday for sure some start promoting you putting your any other new picture any any Why don’t you send it to me I’ve updated ones you know,
Bill Clearfield 1:43:23
you know, you know, as time as time goes on, I get I get more you know, get more and more agents. So, yeah, and I use the ones from the, from the from when I was in my 40s that they look better. So, okay, I’ll do that. Okay. Okay, so, so on Monday night, I’m Dr. Losses group. I’m going to be talking about the new face of weight loss so and so some of the some of the things we’re doing in our office and some of the some of the newer, you know, some some of the new newer modalities that are out and some of the things we found that really been game changers. So we’ve been doing weight loss for 40 years and I’ll bring it to this group to it. I’m to fill in when we can’t find a speaker but we’ve been doing really well here we are really a couple of months out. And we’ve been that way so so I’m appreciate everybody’s time, effort and interest. And again, Doctor good now. You know, please come back. We have you on our on our mailing list now. And when you have time, we’ll be here every Tuesday from now until we’re not but
1:44:34
yeah, I’ll definitely pop in when I can. Yeah, this is fun.
Bill Clearfield 1:44:37
Yeah. Okay. Yeah. So again, so Brian, Dr. Brian Evans next week, is it integrative integrative interventional radiology. So it’s again, I think something that most of us in this group were not participants in, but it should be interesting. So with that, thank you all again, so much, and we’ll see you next week. Same time, same station, and Doctor good now again, great talk and we’ll definitely be be, you know, contact us to contact you for some more information.
1:45:09
Great. Cheers, everybody. Goodnight.
1:45:12
Thank you so much.