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Cyclodextrin Therapy to Rapidly Reverse Atherosclerotic
Dr. Roberts' Cavadex Interview
Within our paradigm, that of Integrative Cardiology,
the focus is risk factor reduction, not to directly reverse anatomic
atherosclerosis, but rather to prevent plaque progression or plaque activation –
and thus to protect you from
clinical events (heart attack, angina, and heart failure).
Our innate physiology does provide for Reverse Cholesterol Transport (RCT), the actual removal of lipid material from the arterial wall. RCT will decrease plaque size and plaque vulnerability. We can stimulate RCT indirectly with tight risk factor control, and directly with PPC (Polyenylphosphatidylcholine – discussed in detail on heartfixer.com).
Beta-Hydroxypropyl Cyclodextrin (which we will refer to as CD, available as CavadexÔ) is a novel, negligible risk, FDA cleared for human use, and relatively low-cost approach to actively stimulate RCT, attenuating ischemic symptoms rapidly while providing a favorable effect (in months, as opposed to years) on plaque size and extent.
CD, first administered IV to humans in 1992, consists of seven glucose molecules bound head-to-tail to form a cone like structure. The exterior of the cone is water soluble (hydrophilic; thus, it disperses within the blood stream) while its interior is fat soluble. CD can thus be used (and is), as a drug delivery vehicle or vaccine component. One molecule of cholesterol fits tightly within the lipid soluble interior of one CD. If we mixed CD with cholesterol, the resulting product would transport cholesterol into your cells, promoting cellular lipid overload. Conversely, as we administer unloaded CD, IV or rectally, we will facilitate egress of cholesterol (and other undesirable lipid structures) out of the artery wall, and then out of the body, via the liver (attached to HDL) or out through the kidneys (attached to CD).
Clearance of cholesterol (into the urine) with IV CD was described in 1992, but the therapeutic potential of CD was not exploited until 2010, when CD (IV, sub cut, and intrathecal – into the spinal fluid) was used for the first time in the treatment of kids with Nieman-Pick. In this (fortunately rare) autosomal recessive (bad genes from both parents) condition, Nieman-Pick protein (which functions to shuttle cholesterol from one cell compartment to another) is defective. Lipids can enter the cell, but Reverse Cholesterol Transport cannot occur. Liver and spleen lipid engorgement occurs early in life, with neurologic compromise following soon after due to brain lipid overload. CD does not cross the blood brain barrier. Thus, in Nieman-Pick, this material is infused into the CSF (cerebrospinal fluid), to treat the brain, with concomitant IV or subcut administration to treat the other internal organs. Hearing loss typically occurs (a fair trade off), but this relates only to intrathecal CD delivery; IV or rectal CD will not cross into the brain and thus will not affect hearing.
So how does this work? Cholesterol can diffuse out of the cell membrane (a bilayer of cholesterol, fatty acids, enzymes, pumps, and pores that surrounds our cells) and then attach to a cholesterol receiver (HDL, albumin, or a red blood cell, but this process occurs ever so slowly. Cell membrane associated pumps (ABCA1 and ABCG1) and diffusion facilitators (SRB-1) promote egress of cell membrane cholesterol, but these vascular health promoting pathways are compromised in patients with atherosclerosis (the problem is not just too much cholesterol entering the vascular wall, but impaired RCT, such that Mother Nature cannot rectify the resulting imbalance). CD works by facilitating cell membrane cholesterol egress, upregulating the RCT pumps, shuttling cholesterol from the cell membrane to HDL (which carries the cholesterol to the liver) concomitantly diminishing oxidative and inflammatory stress within the vascular wall.
Further explanation is in order:
A. One molecule of CD can “pluck” one molecule of cholesterol from the cell membrane surrounding a vascular cell. From there the cholesterol-loaded CD can be excreted in the urine or CD can transfer its cargo (a single cholesterol molecule) to HDL (HDL can house 100s of cholesterol molecules). In this fashion CD acts as a “shuttle” and HDL as a “sink”, a high-capacity cholesterol acceptor.
B. Excess intracellular cholesterol is stored as cholesterol ester (cholesterol bound to a fatty acid). Cholesterol ester is water insoluble; it cannot diffuse out of the cell and creates intracellular lipid droplets (soft plaque). Acetyl-Cholesterol Acyl Transferase (ACAT), upregulated by inflammatory mediators, converts free cholesterol (FC) into cholesterol ester (CE), while Cholesterol Esterase (upregulated by therapeutic PPC) dissolves CE to liberate free cholesterol (FC) which can then egress the cell. As CD decreases cell membrane FC, a gradient is created between the concentration of FC in the cell membrane and that within the cell fluid. ACAT will be turned down and CE activated. Lipid droplet esterified cholesterol is thus mobilized to replenish the cell membrane FC pool. With ongoing CD exposure, intracellular lipid droplet cholesterol overload will resolve.
C. Within the atherosclerotic vascular wall, cholesterol is also stored, within cells and between cells, in crystalline form. Crystalline cholesterol stimulates plaque inflammation (via activation of the NLRP3 inflammasome, a plaque destabilizing pathway which we block with Colchicine -discussed on this website). Foam cells (activated vascular wall mononuclear white cells, endothelial, and smooth muscle cells) will pinocytose (“drink in”) CD. The now intracellular CD will dissolve the crystalline cholesterol, creating a class of compounds termed oxysterols. Oxysterols, in turn, increase the expression of a class of molecules (ATP binding cassette proteins ABCA1 and ABCG1) that pump FC out of the cell, making them available for HDL binding. ABCA1 and ABCG1 promote HDL maturation and enlargement (here size does matter, as HDL efficiency correlates directly with HDL particle size). ABCA1 and ABCG1 activation also rapidly turns down vascular inflammation.
D. At this point CD is pulling, and the activated cassette proteins are pumping cholesterol (liberated from their prior liquid and crystalline states) out of the vascular wall. FC is “handed off” to HDL, where it is esterified (a process stimulated by therapeutic PPC) with subsequent transport to the liver for subsequent GI tract excretion.
E. CD changes vascular anatomy (cholesterol depletion) and it also changes vascular physiology. The removal of cholesterol crystals greatly diminishes vascular wall inflammation (like taking colchicine). CD will also “pluck” diacylglycerols (DAGs) from the cell membrane. DAGs inhibit Nitric Oxide Synthase (NOS), the enzymes responsible for NO generation and thus endothelial tone. Endothelial function improves, leading to vasodilation and (in the setting of occlusive vascular disease) collateral formation.
F. In animal models, CD reduces plaque size and plaque inflammation. Recovery from ischemic insult is enhanced (CD will remove pro-inflammatory lipid debris from the site of injury). Fatty liver (and in diabetics fatty kidney) will improve. CD does not inhibit LDL generation, but as fatty liver attenuates, liver inflammation and cholesterol generation may likewise decline.
CD can be administered IV (6 gm. infused over 30 minutes; I receive this during our lunch break), or rectally, 2 gm/dose, taken over 30-90 days. I first learned about CD in 7 /22 (from a patient, as usual). Intrigued, I read every basic science paper I could find (as far back as 1992), and I made contact with the CavadexÔ team, in the US and in Australia (they call you “mate”). The first person treated was myself (I can’t tell that the IV CD is even going in), and then we began rectal CD therapy in a group of patients with prior heart attack and persistent angina on the basis of failed revascularization (their backs were “up against the wall”). These long-standing angina patients reported symptomatic benefit in 2-4 weeks. Thus, 2-3 months of CD makes sense for all of our patients with symptomatic atherosclerotic vascular insufficiency.
This positive early experience, mirroring the effect of CD in animal models, has led to my recommendation that all of you with moderate plaque buildup consider a 1–2-month CD program. You won’t feel better, but your plaque volume and plaque inflammation will fall, a preemptive attack on atherosclerosis that developed in the past and which may advance despite out best preventive efforts. Indeed, risk factor control is problematic for many of you (you can’t tolerate lipid-lowering therapy or there are cost constraints). CD is well tolerated, totally safe, and cost is not excessive (in a sense CD is the universal antidote for atherosclerosis). My thinking here is that 1-2 months of CD every year will “make up” for any imperfections in our risk factor control efforts.
CD is manufactured and distributed by Cholrem (whose US office is in Salt Lake City). Their website (www.cholrem.com) certainly expands on the information provided here. Cost is $220 for 30 doses (you get $10 off with the password “heartfixer”). The CD provided by Cholrem (the only preparation that I recommend), has been distributed under the trade names of CavadexÔ, RemcholÔ, and CavadextrinÔ; its all the same thing. A prescription is not required (it is FDA cleared and considered safe for human use).
IV CD is administered via a butterfly needle, and the infusion runs in over 30 min. IV CD stays in your circulation over six hours. Thus, if the goal is rapid reversal of atherosclerosis, IV CD could be administered every 8-12 hours. This is what Kyle (the man on the website) did to reverse his RCA plaque. From a practical viewpoint, IV CD could be administered in the office 1-2 times a day, M, W, and F. Cost will be $130/infusion. Thus, daily rectal CD makes more sense.
PPC will synergize with CD. We provide PPC IV, and it can be taken orally (as PhosChol or Plaquex, or mixed with EDTA as DeToxMax). I take one tsp. of PhosChol (2,700 mg) daily to compliment my periodic IV CD infusions.
This is a great idea, and its widespread application will help millions of Americans and save billions of health care dollars. As CD is not patentable, formal research to “prove” efficacy may never be done. Thus, CD will never be covered by insurance and standard Medicine will ignore its potential. The questions in my mind are:
A. How long should a course of CD last?
B. At what time interval should we repeat it?
C. How can we measure efficacy?
I am now in communication with Australian practitioners, and we will continue to gain experience, such that these questions can be best answered. Right now, given the safety, low cost, and obvious efficacy of CD, my recommendation is:
A. In the setting of symptomatic atherosclerosis, 2-3 months of CD makes sense, with end-treatment labs followed by an office visit. 1-2 months of CD twice a wear to further attenuate plaque build-up and to prevent the recurrence of symptoms will be discussed.
B. In asymptomatic patients with moderate plaque, we can start with 1-2 months of CD, and in relation to your lab/non-invasive test results, one additional month 1-2 times/year.
C. Keeping in mind that CD does not remove the underlying causes of atherosclerosis, ongoing risk factor reduction remains important, but with the benefits of CD, we may be able to cut back on the drugs which are most problematic to you.
D. We can carry out periodic CIMT (Carotid Intima-Media Thickness) scans, stress tests, or Coronary Calcium Scoring, but we really don’t know how the subtle (but positive) effects of CD will affect these measurements (which cost a lot more than one month of CD).
James C. Roberts MD FACC FAARFM 10/10/23
As time allows, I will add to this discussion and later create a You Tube presentation on Cyclodextrin. Everyone with atherosclerosis needs to be aware of its benefits (go ahead and tell your friends)!
Rapid Regression of Carotid Plaque
Carotid Intima-Media Thickness testing (CIMT), my favorite measuring stick as to the current vascular status, is discussed in detail elsewhere on this website. The greater your IMT, and the greater the rate of IMT progression, the more rapidly are you generating new plaque and the more likely are you to experience a clinical event. Conversely, if we stabilize or regress your IMT, then event risk is low (we are turning the ship around). The CIMT study does not visualize the deeper regions of your internal carotid arteries, nor does it estimate their degree of narrowing (here we would us the standard carotid ultrasound), but the CIMT study does visualize the common carotids and carotid bulbs, and here we can assess changes in plaque burden.
SM, now in her mid-60s, is incredibly health conscious, a good thing in that she bears genomic hyperlipidemia, with a 2011 baseline LDL of 194 mg/dl. With RYRE 2,400 mg and Berberine 1,000 mg/day, LDL fell to125 mg/dl, at which time SM's baseline IMT study was carried out. As plaque was identified, we switched from RYRE to Rosuvastatin 10 mg/day (keeping Berberine on board), and with this LDL dropped to 102 in 4/22. Myalgia then occurred, prompting a switch to Pravastatin 20 mg/day, which didn't work as well, with a 12/22 LDL of 182. Given our inability to control SM's hyperlipidemia, SM received two months of CD therapy, without difficulty. SM's IMT study was then repeated, demonstrating a regression of IMT (a very positive sign) and to my eye, a regression of carotid plaque. Being intellectually honest (I don't work for the government and thus honesty is expected) the three-year improvement in SM's IMT findings could relate to all of the other, non-lipid reduction maneuvers that SM has been carrying out, but with these measures alone I rarely if ever see visible plaque regression. In animal models (and in Kyle on the cavadexusa.com website) visible plaque regression may occur within months, and thus this dramatic change in SM's findings likely reflect CD therapy. Our tentative plan is for SM to complete one months of CD twice a year, with periodic IMT reassessments.
Baseline Study in 3/20 Post-Cyclodextrin therapy in 2/23
This represents a reversal of IMT (the current status of one's vascular biology) and a regression of atherosclerosis (that developed over decades), utilizing a well tolerated, safe, and relatively inexpensive (invasive revascularization costs a minimum of $10K) therapy. Now, SM's myalgia was later found to be due to fibromyalgia, which is responding to physical therapy, and thus she is going to resume Rosuvastatin, which should help in the long-term, and which should synergize with future rounds of CD therapy. SM's outlook, despite genomic hyperlipidemia, is certainly positive now, now that we have found a means of reversing her atherosclerosis.
Turning the Atherosclerotic Ship Around with Lipid Reduction and Cyclodextrin
JB, a now 70 year-old health care provider, experienced a limited heart attack in 1/16, requiring RCA (right coronary artery, which supplies blood to the back wall of the heart) stent placement (two sites). Symptoms recurred in 11/16; the RCA stents were open but the LAD (left anterior descending, which serves the front wall of the heart) had rapidly progressed to 95%, necessitating stent placement, and the same for a now flow-restrictive circumflex marginal (side wall of the heart) branch narrowing. Dr. JB and I began working together in early '21. Dr. JB's IMT was above-average-for-age, as you would expect, and moderate common carotid plaque was identified. Dr. JB's LDL was in the 170's, but pharmaceutical statin therapy (atorvastatin) led to debilitating brain fog. We switched to a program of RYRE (non-drug statin agent) 1,200 mg. Berberine (non-drug PCSK9 inhibitor and insulin sensitizer)1000 mg. and a Tocotrienol at 150 mg/day. This lowered DR. JB's LDL to 124 mg/dl, but this was too little too late, as by 8/21 three new symptomatic narrowings had developed within the RCA, each requiring stent placement (at this point Dr. JB bears seven stents). Blurred vision post-stent placement led to cerebral angiography, demonstrating a high-grade narrowing in the basilar artery (serves the back of the brain and not amenable to stent placement),
We redoubled our efforts. With rosuvastatin 20 mg and berberine 10000 mg/day, Dr. JB's LDL dropped to 73 mg/dl, but he could barely function. Repatha (pharmaceutical PCSK9 inhibitor) 140 mg every two weeks, along with Berberine and rosuvastatin at a reduced dose of 5 mg/day lowered Dr. JB's LDL to 10 mg/dl, way to low, and this program with rosuvastatin at 2.5 mg led to a LDL of 16 mg/dl, still with brain fog. In the fall of '22 we switched to a program of Repatha every three weeks, combined with a Tocotrienol ( and no berberine or statin). Dr. JB tolerates this program well and LDL was right on target at 55 mg/dl, with favorable particle size. We had been covering the other bases of atherosclerosis management, utilizing Colchicine (protects against plaque activation), DeToxMax (metal detoxification and PPC to stimulate reverse cholesterol transport), Jiagolan to lower TMAO, and CPAP was on board for sleep apnea control.
To this regimen, in early '23, Dr. JB added three months of daily Cyclodextrin therapy. Dr. JB remains asymptomatic, brain fog is now far less of an issue, and, just as in the case of SM, described above, we identified regression of IMT and regression of carotid distribution plaque volume (also likely occurring though out Dr. JB's entire vasculature). We cannot attribute all of this change to three months of Cavadex, but we are sort of a "all of the above" cardiovascular practice, and thus we do not need to. Dr. JB's program will be continued, likely with one months of Cyclodextrin theapy, every four months, to further stimulate reverse cholesterol transport and thus further reduce plaque burden.
Baseline Study in 3/21 Post-Cyclodextrin therapy in 3/23
Cyclodextrin Controls Hypertension in Renal Artery Stenosis
Renal artery stenosis (RAS), a flow-limiting atherosclerotic narrowing in the artery serving the kidney(s), is an important "secondary" cause of hypertension. In this situation blood flow to the kidney is compromised. The kidney senses this as low blood pressure (such as due to dehydration or salt deficiency) and responds by elaborating vasoconstricting mediators (such as norepinephrine) and salt-retaining hormones (such as renin). We suspect atherosclerotic RAS when a patient with previously stable BP values experiences a sudden loss of BP control.
LJ, who has been received medical
therapy for HTN for well over a decade, underwent an extensive cardiovascular
evaluation in 2009, demonstrating mild left ventricular pump dysfunction, mild
coronary atherosclerosis, and clear renal arteries. Medical therapy was
initiated, and adequate BP control achieved. LJ and I began working
together in 8/22. At that time her office BP was elevated at 170/90 mmHg,
despite a program of Losartan 100 mg (an angiotensin receptor blocker),
Nisoldipine 8.5 mg (which blocks the calcium channel), Atenolol 50 mg (a
beta-adrenergic blocker), and Spironolactone 25 mg (blocks adrenal aldosterone
salt retention), all once a day.
Losartan was advanced to 150 mg/day and Spironolactone to 50 mg/day, and with these measures BP was 150/86 in 10/22. LJ was watching her diet, sleep apnea had previously been excluded, and endothelial function looked great (EndoPATscore of 4.2). Suspecting that RAS might be playing a role, a renal artery ultrasound study was carried, returning with findings of right sided RAS. In this situation, refractory (not responding to multi-drug therapy) HTN, renal angiography with stent placement would be the next logical step. But given the favorable response that our patients with coronary and peripheral vascular disease were experiencing with Cyclodextrin (CD), we decided to first to try to open up the renal artery by stimulating RCT (reverse cholesterol transport) with CD. As the adequacy of blood flow relates to the square of the vessel's radius, even small improvements in renal artery flow could lead to a major reduction in RAS pathophysiology.
The plan worked (and why shouldn't
it)?. At two months, BP was 130/78, and we constructed a plan to back off
on medical therapy if BP fell to low. Repeat ultrasound returned with
non-definitive findings, still describing high flow velocity (suggesting a
narrowing) in the right renal artery, but also suggesting that this might be a
false-positive sign, related to technical difficulties in data acquisitions (it
is often difficult to direct the doppler region of interest at just the right
spot). To be definitive we would need to carry our a renal artery imaging
study, but that would be just to satisfy our curiosity, as LJ's clinical
problem, refractory hypertension, was coming under control.
We re taking aim at all causes of LJ's atherosclerosis (her LDL has decreased from 158 to 128 and CRP from 2.6 to 1.8 and we have more work to do here), and LJ will continue with CD, 1-2 doses per week, and medical therapy will be adjusted as needed. It is possible that LJ's BP improved by a different mechanism, but CD alone, even thought it removes cholesterol from the vessel wall, alone should not lower BP. In some patients BP values wax and wane, almost in a seasonal fashion, and sometimes we just get lucky. In any event, LJ is doing better, and CD maintenance therapy will be continued.
Cyclodextrin Rapidly Improves Endothelial Function and Vascular Symptoms
Visible to the eye, plaque regression, can occur with CD, in months as opposed to years, but ischemic symptoms (effort angina or claudication) often attenuate within weeks. In explaining this anatomic-symptomatic disconnect, we need to remember that angina symptoms relate to all of the following:
A. The absolute degree of vascular narrowing (angina should be worse with a 90% as opposed to 70% narrowing).
B. The presence or absence of collateral flow (if a vessel closes slowly, a natural collateral bypass network will develop – or we can generate collateral flow with EECP).
C. The ability of the endothelium to generate Nitric Oxide, our natural vasodilator.
D. The ambient levels of oxidative (superoxide, peroxynitrite, etc) stress and inflammatory (Th1 cytokines such as Il-6 and Il-1b) chemical mediators that compromise endothelial tone.
E. “Conditioning” the innate ability of the heart (or leg) muscle to tolerate oxygen deficiency (discussed in the Ouabain section).
CD probably does not have a Ouabain-like conditioning effect, but CD does have a favorable effect on symptom determinants A through D. Below we will review the mechanisms through which CD rapidly normalizes endothelial function, within the context of a case study (CH).
Endothelial Function (discussed in detail in the Endothelial Function section) is a critical determinant of short and long-term cardiovascular outcome. Treatments that resolve symptoms without improving endothelial function, in general, do not protect against future adverse events. Conversely, essentially all therapies that improve endothelial function symptoms as they attenuate symptoms will protect you from future events (heart attack, stroke, unstable angina, etc.). To this list we can add Cyclodextrin.
We assess endothelial function by measuring flow-mediated vasodilation (EndoPAT methodology), discussed in greater detail elsewhere on this website. A normal score is > 1.7, but as heightened endothelial tone may compensate for sub-optimal risk factor control, the higher the EndoPAT score, the better.
CH, who looks younger than her stated age of 82 years (I say this about all of my female patients, but in CH's case it is true), presented in mid-’21 with progressive intermittent claudication (leg pain with effort on the basis of lower extremity vascular disease), and an asymptomatic high grade (80-99%) right internal carotid narrowing, with a less critical 50-79% narrowing of the left. We compare BP at the arm (brachial artery) with that at the ankle (Ankle-Brachial Index, or ABI) to assess the adequacy of lower extremity blood flow. An ABI of 1.0 is normal; the lower the values, the worse the degree of vascular insufficiency. CH’s right lower extremity ABI was 0.73, dropping to 0.25 following exercise, with corresponding left sided values of 0.90 and 0.75.
Claudication is a limitation while a stroke can change your life, so our plan was for CH to undergo right carotid surgery (carotid artery endarterectomy – CEA), followed by lower extremity vascular surgery at a later date.
CH’s baseline LDL cholesterol was 158, dropping to 95 with RYRE 2,400 and Berberine 1,000 mg/day. Attempts to substitute in Atorvastatin or Rosuvastatin led to severe myalgia. CH’s Lp(a) was elevated at 74, which we addressed with lysine and proline supplementation. CH’s BP, glucose, and homocysteine levels were pristine.
Right CEA went off without a hitch, but several weeks later CH experienced left sided weakness, followed by a seizure and change in level of consciousness. Imaging suggested dissection (a tear) at the surgical site, but blood flow through the right carotid was unimpaired. MRI demonstrates relative hyperperfusion (excessive blood flow) within the right side of CH’s brain, an unusual complication of CEA, a “reperfusion phenomena”.
Left sided weakness slowly resolved, but CH was left with brain fog and depression. We carried out several Relox Stroke Recovery treatments (see www.drrind.com), and with this CH’s mood and brain fog improved. CH, however, was left with an impairment and of course claudication was no better.
At this point CH began a three month program of daily CD. CH’s mood rapidly brightened, mental clarity returned, and claudication is no longer limiting.
Endothelial function, certainly adequate at baseline (2.81 in 8/21) improved to 3.88 on CD.
Why did brain fog and mood improve? With a stroke, there is an explosion of brain cell lipids and myelin. Macrophages (“big eaters”) infiltrate the area, ingest the lipid debris, and then take on the characteristics of lipid-rich foam cells, the same cytokine secreting foam cells that mediated atherosclerotic vascular inflammation within coronary plaques. Inflammatory cytokines generated in the peri-stroke zone will diffuse into the midline hippocampus region, affecting short-term memory and mood. The problem here is excessive lipid debris, and our bodies maladaptive way to clear it (with foam cells). No disrespect to Mother Nature, but we have a better way to clearing lipid debris – Cyclodextrin!
While CD is not felt to cross the blood–brain barrier, it does reach the cerebral circulation, and likely enters the peri-stroke zone (where the blood-brain barrier has been breached). In an animal model (surgical ligation of the middle cerebral artery) CD promoted lipid clearance and blunted the spread of inflammatory cytokines. The animals treated with CD returned to their normal behavior patterns more readily. My thinking here is that CD cleared residual lipid debris from CH’s right hemispheric stroke zone, accelerating her recovery, while at the same time generating nitric oxide and improving blood flow to her lower extremities.
Standard medicine focuses on vascular “lesions” isolated blockage to be addressed with surgical procedures. If a number of blockages are present, then a number of sequential surgical procedure will be carried out.
In Integrative Cardiology, we have a better idea. We can use CD (and related agents) to restore vascular biology as we decrease plaque volume throughout the body.
Our tentative plan will be for CH to continue her standard risk factor reduction program, and to complete four weeks of CD twice a year; more frequently if there is a hint of symptomatic recurrence. CH’s non-invasive studies will be repeated at the one year point.
Cyclodextrin for Post-EECP Refractory Angina
SC joined our practice roughly 25 years ago, soon
after we brought EECP to NW Ohio. SC sustained two heart attacks in the
80's. Failed angioplasty in 9/96 led to two-vessel bypass surgery, and since
then SC has required four angiographic studies, a second round of bypass surgery
in 3/05, and, through 2020, two rounds of EECP. Needless to say, a
comprehensive approach to risk factor reduction (BP, glucose, lipids, etc.) has
been carried out.
Angina worsened in the fall of '20. Angiography demonstrated a patent LIMA graft to SC's occluded LAD (left anterior descending, which serves the front wall of the heart), a patent SVG (saphenous vein graft) to the occluded Circumflex (serves the side wall of the heart), occlusion of the RCA (right coronary artery, which serves the back wall of the heart) and its SVG as well as closure of the SVG to the Diagonal (which runes parallel to the LAD).
Further mechanical intervention was not possible; thus in early '21 SC received 35 hours of EECP, which attenuated, just did not totally resolve, SC's ischemic symptoms symptoms (particularly intolerance to walking in the cold). Soon thereafter we learned about Ouabain (discussed elsewhere on this website - Ouabain renders the heart more tolerant to oxygen deficiency - it makes us into "pearl divers"). and this agent was added, with an incremental benefit.
Last fall, as the weather turned chilly, SC's angina worsened; walking to his work shop led to predictable chest pain. Repeat angiography would not change our actions, and thus EECP was repeated. SC improved, but walking to his shop in the cold still brought on chest pain. At this point I was becoming increasing confidant in CD, and thus asked SC to begin a three- month program of CD supplementation.
By day four SC was feeling better, and after three months, while angina may still occur with a brisk walk in the cold, NTG is no longer required. How can this be? By day four we can't be opening up a narrowed artery, and we would not expect CD (or any other therapy) to restore flow through a chronically occluded vessel (native artery or bypass graft). What is happening here (and I am seeing this in other patients) is that while CD only slowly opens up narrowed arteries, via its mechanisms of action (discussed above) CD rapidly turns around abnormal vascular biology. CD rapidly disinhibits NOS (Nitric Oxide Synthase) turning one into a NO (Nitric Oxide) factory (why EndoPAT scores improve). Vascular wall oxidative and inflammatory stress all recede. As your symptoms reflect your biochemistry as much as your anatomy, you respond rapidly to CD. We then continue some form of maintenance CD therapy, combined with intensive risk factor reduction, in an effort to further open up your vessels.
Cyclodextrin for Angina with Open Stents
It is not unusual for individuals to experience
chest tightness post-stent placement, in the absence of angiographic narrowing.
Stent placement leads to endothelial dysfunction and this nitric oxide
deficiency can compromise coronary perfusion, There is also the issue of
microvascular ischemia (discussed in the Ouabain section). Other mechanisms may
also be playing a role here. HC has post-open stent angina that resolved
with four weeks of CD.
HC and I met in 2014, when HC's symptoms were primarily neurological (brain fog, tremors, drop attacks) felt to be due to cobalt toxicity. Metal-on-metal artificial hips had been placed, The alignment was off and the cobalt ground off into HC's system, with devastating effect. The cobalt hips were removed and replaced with a composite material, and cobalt chelation was initiated (here we were limited as HC's insurer would not cover the cost - they paid doctors to put a poisonous substance into HC but they wouldn't cover the cost of its removal)! We did what we could and HC's neurologic symptoms have decreased, but over the years he has developed thyroid, adrenal, and androgen deficiency, likely also cobalt related.
HC experienced chest tightness in 2015. His chemical stress test (Lexiscan) returned falsely normal, as soon thereafter HC experienced a small heat attack. necessitating two vessel stent placement. Over the years chest pain has waxed and waned, sometimes NTG or Ouabain responsive, and sometimes not, Four nuclear stress tests have been carried out, all normal, and four angiograms, some showing patent stent sites and others showing new narrowings (to this point four stents have been placed). EECP would help, and here we were likely helping HC to generate nitric oxide generation as opposed to stimulating collateral generation.
HC was feeling poorly in 12/22. with recurrent pain despite EECP in the early fall. Given how well our other patients were doing with CD, and my new appreciation that CD rapidly generates nitric oxide and lowers inflammation as it removes vascular wall lipids, I asked HC to try this approach.
It worked! At four weeks HC is feeling better on multiple fronts. I do not think that plaque regression was the mechanism of benefit, but rather a CD-induced resolution of oxidative/inflammatory vascular wall biology. HC will complete a second month, and then our tentative plan will be for HC to receive one month of CD twice a year (and hopefully no more heart caths).
Physician DePlaque Thyself!
Carotid Intima-Media Thickness (IMT) is discussed in detail elsewhere on this site. IMT is not plaque, but rather the thickness of the artery wall (endothelial and muscular layers) within a normal appearing region of the common carotid artery. IMT is a systemic measurement, the "staging ground" of plaque formation. IMT reflects the status of your vasculature, with respect to forming new plaque over time, and your risk of experiencing an adverse cardiovascular event. IMT changes over 6-12 months, in relation to your risk factor situation. You want a low, and preferably decreasing IMT value. We use change in IMT, over a 1-2 year time frame, to assess the success (or failure) of our anti-atherosclerotic interventions.
We obtained our IMT machine in the summer of '08. My IMT was 0.671 mm, at the 50th percentile for American Men in my age range. On the right side, my IMT was 0.590, at the 25th percentile, while my left carotid IMT was 0.752, between the 50th and 75th percentile. Flow disparity, related to laminar vs. turbulent flow beyond branch points, may give rise to asymmetric or focal differences in plaque deposition and in IMT, but we did not know this in 2008. My hypothesis then was that asymmetric exposure to ionizing radiation was playing a role. I did a lot (this is all I did early in my career) of invasive procedures, and I wasn't too careful regarding radiation safety (we all do dumb things when we are young). We wear a lead shield over our thyroid gland (well, we are supposed to), but it doesn't totally cover our neck in the region of the carotid artery. I carry out procedures standing at the patient's right side, with the X-ray tube in front of me, and thus my right carotid is protected (by my neck) and my left carotid is more exposed. Radiation can give rise to atherosclerosis, and thus my recommendation to myself then was "to stop doing all those heart catheterizations".
Snap shots of my IMT and common carotid arteries are seen below:
Over the intervening years my focus shifted to comprehensive atherosclerosis management, and thus I no longer carry our invasive procedures. My diet isn't perfect but it has been steadily improving. I work out vigorously 12 hours a week, get at least seven hours of sleep each night, and take a lot of anti-aging and health promoting supplements.
When we learned about Cyclodextrin last summer, my initial thought was to provide this therapy IV (this would not be cost-effective for you and thus we are recommending daily, rectal Cyclodextrin as opposed to intermittent IV Cyclodextrin). Before offering IV Cyclodextrin to patients I thought it best to see how I felt with this approach. I started with IV therapy M, W, and F, receiving IV Cyclodextrin over 30 min. at lunch. However, if the morning was busy, my lunch time IV was skipped, and I took 1-2 week breaks due to vacation (and we all got Covid last Sept). This was more of a hobby/science project for me, and not a critical intervention, so I didn't worry about the schedule.
IMT progresses, in healthy Americans, at a rate of
0.01 mm/year. My IMT has progressed, over 14 years, by 0.1 mm, thus at
a lower than expected rate of 0.007 mm/year, and my new value of 0.771 remained
at the 50th percentile for my age (I am 67 years old). However, common
carotid and carotid bulb plaque had developed, as presented below:
In '08, we were measuring common carotid IMT alone. Subsequently we began to record plaque volume (an approximation) within the (often difficult to visualize) carotid bulbs. While my IMT was not threatening and my rate of IMT progression acceptable, I was not too pleased that this volume of plaque had developed. Also, this is embarrassing. I'm supposed to be this ultra healthy supplement chugging marathon runner! To address this issue my plan was to begin IV Cyclodextrin, with repeat IMT assessments every 5-10 rounds. So what happened?
Well nothing! Plaque volume was unchanged to slightly increased (at least to the naked eye), but this was after only five IV treatments. What surprised me was an actual increase in IMT, from 0.771 to 0.838 mm, which would correlate with an astonishing 0.80 mm/year rate of IMT progression. This would suggest that Cyclodextrin was having an adverse effect on my vascular health. However, Cyclodextrin was resolving angina in my patients (early on by turning on Nitric Oxide production and turning down free radical and inflammatory cytokine production). PPC (phosphatidylcholine, discussed in detail elsewhere on this website) reverses atherosclerosis long-term, but over the short-term PPC may actually increase plaque volume. My interpretation of this finding, and the fact that my IMT had increased significantly with five IV Cyclodextrin treatments, is that cell enlargement was occurring, as the enzymes involved in reverse cholesterol transport increase their expression, and start pumping lipids out of the vascular wall.
Thus I kept up with IV Cavadex, and later added in oral PPC 2,700 mg/day (which I had been taking on and off). We will be involved in a clinical trial of Eztrek (a plant-based essential fatty acid supplement ) in the treatment of atherosclerosis, so I began taking Eztrek, one tsp./day. In late 10/22 I underwent the anti-aging VSEL activation protocol and in 4/23 avian growth factor supplementation was begun (you will hear about all of these approaches when I find the time to create write-ups and/or audio-visual presentations).
As you can see from the above graphic, my IMT steadily climbed, and then began to fall, and is now dropping like a rock. As IMT is the staging ground for atherosclerosis, you would now expect plaque volume (which lags behind) to be decreasing, and that is what happened:
Keeping in mind that we are making "eye ball" two dimensional assessments of a wiggly three dimensional artery, in viewing all of my studies, it did appear that IMT (and possibly plaque volume), initially increased, and then began to decrease. Plaque within my Left Common Carotid has been replaced by IMT, and Carotid Bulb plaque is smaller. The differences are not large, but baseline plague volume itself was relatively small. I am going to stop IV Cyclodextrin after 50 treatments (4/17/23) and repeat my IMT study in three months. My hunch is that my IMT and plaque volume will continue to improve. I think that I have cranked up the enzyme systems involved in reverse cholesterol transport and lowered inflammation and oxidative stress within my vasculature. If I am not happy with my future IMT assessments, of course I may take more IV Cyclodextrin, or possibly add in IV PPC.
The lesson learned here is that it takes time to turn a ship around, and that we should not get upset if one's IMT initially increases on Cyclodextrin. Cyclodextrin thus appears to break our rule that (at least over the short-term) that phenomena that increase IMT are increasing atherosclerosis risk, as with Cyclodextrin therapy IMT may increase before it decreases. I also think that intermittent therapy with 6 gm of IV Cyclodextrin (which I received) is inferior to daily rectal (2 gm) Cyclodextrin. I think that as we are turning the ship around, it makes sense to keep pushing, every day.
Cyclodextrin Rapidly Restores Vascular Biology
In SCs's and HC's case histories, I proposed that short-term benefits in relation to CD therapy relates to biochemical change, while longer-term benefits relate to actually opening up narrowed vessels (not just one vessel at one site, as with stent placement, but at all sites in all vessels). This hypothesis is supported by AD's Cyclodextrin response. AD experienced angina, leading to bypass surgery in 2000. Since then AD has learned a great deal about atherosclerosis, and (like his doctor) keeps close records as to how he responds to new treatments. Three grafts were placed (LIMA to LAD, vein graft to the right sided PDA, and a free radial graft). Pain persisted post-bypass, leading to angiography, which demonstrated a patent LIMA to LAD graft and closure of the two others. AD then began a program of EDTA chelation therapy, and with monthly sessions, angina resolved. In 2014 AD experienced loss of consciousness (syncope), and here angiography demonstrated an element of disease regression in his native vessels.
We began working together in 2019. We kept up with monthly EDTA sessions, but it puzzled me that AD couldn't go longer than four weeks, between sessions, without experiencing angina. We added Ouabain, and this helped, and then we added CD, and with this angina resolved and monthly EDTA was no longer needed. On CD for two months, AD can do whatever he wants.
We then stopped CD, and angina promptly recurred. AD resumed CD, and angina promptly resolved again. AD resumed CD on a two days on-two days off schedule, which he is going to adjust in relation as to how he feels.
This is difficult to explain. we are not opening up
and closing down vessels in relation to on and off CD therapy. Rather the
biochemical/nitric oxide/collateral formation effects of CD must be the
mechanism of AD's improvement. I anticipate that with further CD therapy, AD's
native vessels will open up or collateralization will be enhanced, such that
maintenance therapy is no longer needed. In any event, we have found a solution
to AD's persistent angina.
AD's Journal Notes are available for your review
Cyclodextrin to Improve Endothelial Function and Lower BNP
KM completed a two month program of CD, and didn't feel any better, likely because his coronary disease was already compensated, but BNP (a marker of cardiac stress and strain) fell from 149 (normal is < 100) to 87, and his EndoPAT score rose from 2.91 to 3.54.
KM underwent RCA (Right Coronary Artery) stent placement in 4/01, with a normal follow-up stress EKG study. An abnormal stress test in the fall of '02 lead to angiography, which demonstrated disease progression in the LAD (Left Anterior Descending), with a patent RCA stent. Single vessel LIMA (Left Internal Mammary Artery) to LAD bypass surgery was then carried out. Six years later (in 3/08) stress EKG testing returned markedly abnormal (3 mm ST depression) and CT angiography suggested high-grade narrowings in the RCA and within the LIMA graft. KM and I began working together at that point. A 13:00 stress echo study returned equivocally abnormal in 10/08 and a 13:33 study in 5/09 was normal. To reconcile these discordant studies angiography was carried out, demonstrating a 50% narrowing at the RCA stent site, dysfunction of the LIMA graft, but the LAD itself had opened up, from 70% in '02 to 50%. Five years later, in 7/13, KM began to experience effort-related angina, and his 12:00 stress study returned abnormal. Angiography demonstrated a now 90% narrowing within the RCA stent (in-stent restenosis, a manifestation of scar tissue formation as opposed to atherosclerotic lipid deposition), the LAD was stable at 50%, and the LIMA graft looked better. We intensified our anti-atherosclerotic efforts, 35 hours of EECP was carried out, and subsequently KM picked up his jogging program (aiming to maintain collateral flow). Since then KM's angina has been quiescent and stress studies have demonstrated only borderline ischemia within the RCA distribution, as would be expected in this situation (with a well collateralized single vessel narrowing).
While coronary disease has been stable, KM has developed, over the years, insufficiency of his aortic valve, not severe enough to mandate surgery (if KM's left ventricle begins to dilate excessively or if pump functioned begins to falter, than aortic valve replacement would be appropriate), but enough to slow him down with his running. In case recurrent coronary disease was the culprit, KM completed two months of CD. He didn't feel any better, telling us that ischemia was not the culprit. However endothelial function improved, and BNP, a determinant of cardiac strain, did fall.
In an effort to forestall a deterioration in KM's cardiac status on the basis of aortic insufficiency KM recently received our VSEL activation protocol, aiming to replenish aging/stressed cardiac cells with juvenile replacements (much more on this program, which will revolutionize how we deal with aging and organ damage, in the future). The point of presenting KM's story is that endothelial function, already OK, improved further with CD therapy.