Should LDL be called “bad” Cholesterol? Dr. Nadir Ali
Jun 27, 2020 SHERATON DENVER DOWNTOWN HOTELDr. Nadir Ali is an interventional cardiologist with over 25 years of experience. He is also the chairman of the Department of Cardiology at Clear Lake Regional Medical Center. Before working as a cardiologist, he served as an assistant professor of medicine for eight years at Baylor College of Medicine in Houston, where he also received his medical training. Dr. Ali has championed many aspects of the science and practice of a low-carb lifestyle in the local Clear Lake area since 2013. He organises a monthly nutritional seminar in the Searcy Auditorium of the Clear Lake Hospital that receives more than 100 visitors every month from the local community. Dr Ali’s focus is on managing heart disease, obesity, metabolic syndrome and diabetes. Please consider supporting Low Carb Down Under via Patreon. A small monthly contribution will assist in the costs of filming and editing these presentations and will allow us to keep producing high quality content free from advertising.
Transcript
Intro
0:01[Music]
0:21my disclosures are that in a moment of weakness Jason Fong and Megan Ramos decided to
0:27include me as a part of IDM and the
0:32fasting method and if there is any statin police out there I want to make aWhat is cholesterol
0:38disclosure that I am NOT giving individual medical advice and
0:44occasionally I do prescribe statins so you have seen this slide before fat and
0:53cholesterol are vacci substances they do not dissolve in blood our blood is
0:59Acuras of watery and in order to carry cholesterol it creates these lipoprotein
1:04particles that have an outer coat that dissolves in blood and they have identifying proteins that give it a
1:12functionality so I wanted to go over what functions the lipoproteins do and IFunctions of cholesterol
1:22thought one slide would be enough but what we need to recognize is that there
1:28is millions of years of evolutionary engineering behind creating these
1:34molecules so that they help us with host defense they fight bacteria they mop up
1:44bacterial products they modulate inflammation cholesterol is not a
1:51metabolic fuel you cannot burn it and it has to be removed and it’s removed in
1:57the biliary tree it’s the life of proteins that create a cholesterol balance when your cells are damaged
2:05cells need to be repaired and it’s the life of protein molecules that do that so I thought one slide would be enough
2:13but it was not so I had to create a second slide to show that the
2:20cholesterol is important in processing or functionality of your insulin
2:27receptor depends on cholesterol because cholesterol rich domains give it
2:33the structure it needs to function our sex hormones the LDL surprise the raw
2:41materials for the sex hormones to be made it’s a carrier for fat soluble vitamins
2:49Dave Feldman has talked about energy delivery it is the lipoprotein molecules
2:55that deliver energy the kakouton which is an important part of our muscle
3:00function is delivered through the lipoproteins and who knew that
3:08prevention of vascular calcification that Jeff was talking about is also
3:13modulated because cholesterol is involved in converting vitamin K 1 to K
3:202 which prevents vascular calcification so the question we should ask is that
3:28should I ampere with these lipoproteins in general or LDL or LDL in particular
3:35when millions of years of evolutionary engineering has given it so many
3:42different biologic functions that I have pointed out and this list by no means is
3:51complete what we need to recognize is
3:56that Nature has already done some of this for us and it has created a
4:02situation which is called a better lipoprotein emia in which the LDL is
4:07absent so we should think that a person with an absent LDL should live forever
4:13so when we look at a group of these individuals let’s see what happens theyWhat happens to people with high cholesterol
4:20have a failure to thrive they get recurrent infections they get blindness
4:26they get issues with regards to their neuromuscular function in other words
4:35movement disorders they get a fatty liver and instead of living forever they
4:40die in their third or fourth decade the that the lipoprotein molecules are
4:46important in supplying cholesterol to your nerves in carrying fat soluble
4:52vitamins in fighting infections but as
4:58it so happens we don’t want to learn from nature’s mistakes we want to do our
5:04own and that’s why we started this era
5:09of statins and a new drug which is called pcsk9 and hopefully I’ll have time to get into that now cholesterol isHow does cholesterol work
5:18vitally important for us if you ate no cholesterol and you became a complete
5:24vegan your body will still make 300
5:293,000 milligrams of cholesterol every day 3 grams 3,000 milligrams there’s a
5:37synthetic machinery that our body has to make cholesterol and while it’s making cholesterol it also makes certain very
5:44important molecules that have biologic function now statins prevent cholesterol
5:51production very high up in the chain of this cascade so what we noticed is that
5:59isopentenyl is making us certain proteins called solano proteins that
6:06give us antioxidant protection it’s converting vitamin K 1 to K 2 that
6:13prevents vascular calcification kakouton is important because it helps muscle
6:20function dalek all which is cholesterol precursor is helping us process the
6:28insulin receptor and cholesterol itself is involved in giving the membrane the
6:34integrity that it needs so I have been
6:40accused of being very nerdy and that was quite nerdy so how do i unpack this how
6:47do I be redundant so to reiterate the isopentenyl is involved in creating
6:54certain antioxidative enzyme that prevent free radical damage that
6:59the isopentenyl converts K 1 to K 2 so that vascular calcification is prevented
7:05that kakouton is involved in muscle function that dolly call is processing
7:11the insulin receptor and cholesterol itself is providing certain cholesterol
7:17rich domains so that receptors can function and here is an example of an
7:24insulin receptor the insulin receptor sits in caviola which is a cholesterol
7:30rich domain and in that cholesterol rich domain the receptor functions well
7:37because it has the structural integrity when you remove the cholesterol the
7:42insulin receptor does not function well as we shall see later now we talked
7:49about dalek all as a precursor for cholesterol production and dalek all is
7:55involved it takes the protein manufacturing machinery of the body and in that location where the insulin
8:03receptor is being made it attaches a sugar residue so that the receptor can
8:09function well so cholesterol is involved
8:15in every step of the way for processing of the insulin receptor at the level of
8:22the membrane it sits in a cholesterol rich domain the sugar residue is through
8:29Dalek halt or cholesterol intermediate and the pore through which the channel
8:36through which the body takes in sugar the glute 4 channel is also processed
8:42through the solano proteins made by cholesterol so is this all justClinical relevance of statins
8:49biochemistry or is there any clinical relevance to this and the clinical relevance to this is coming from the
8:57Women’s Health Initiative study 10,000 of these women were on statins 140 were
9:04not what happened the women that were in statins three years later
9:10the chances of beat them being a diabetic was a little close to 10%
9:15compared to 6% in women not taking statins a three point five percent
9:21difference if you were a Hispanic you are more susceptible to statin damage
9:28and the difference was not three point five percent it was five percent if you
9:33were a nation like me the difference was not three point five percent it was seven percent now we’ve talked about
9:41coq10 a lot the way I talk about coq10 is that it is the spark plug of an
9:49engine if the engine doesn’t have spark plug it cannot burn fuel similarly for
9:54mitochondria I don’t have Co Q 10 they cannot create usable energy which is called ATP and Co Q 10 is a cholesterol
10:02by-product so my fellow Texan dr. Lance Joan took ten patients who were on
10:10statins heated muscle biopsies here at blood work and he compared them to nine
10:16matched controls and out in the blue line what you’re seeing is how the match
10:23controls performed and compared to that blue line the people who we’re on
10:29statins had higher blood pressure higher sugars they had lower kakouton in their
10:38muscles they made less enzymes that
10:43prevented oxidative damage of free radical damage they were not able to
10:48generate the energy currency because they didn’t have Co Q 10 and they were insulin resistant so dr. Lance Truman
10:58took 328 patients that present it to his office and we’re on statins and he found
11:04that 50 of these patients complained that they were having myalgias that they
11:09were fatigued that they were having shortness of breath that they were having memory issues and he stopped
11:16their statins and when he stopped their statins majority of them improved in 28
11:24these patients they had heart muscle dysfunction that he evaluated with an ultrasound of the heart called an
11:29echocardiogram when he stopped the statins 50% of these individuals
11:35improved the other 50% did not improve
11:40which means that statins physician of statins may not lead to improvement in
11:46everyone so it this is something thatDo statins prevent heart failure
11:52was not good information for the statin industry and what they did is to say hey
11:59let’s go on offense and say that using statins will prevent mortality in people
12:05who have congestive heart failure heart failure is a situation in which the heart muscle is not pumping well so what
12:12they did is to compare people who had heart failure who were on statins compared to who we’re not on statins and
12:19this is an unfair comparison because if you to bring me a patient with heart
12:24failure and they have high cholesterol I know they’re going to live forever a proper way to compare is to see the
12:32group of people who are on statins if they are taking statins less frequently
12:38in the middle or taking it more than 75% of the time who does better and that’s
12:47the comparison I did so if you were taking statins less frequently you are
12:53less likely to die in fact the highest mortality was there in the group that took the statins most of the time not
13:01just all cause mortality you were at greater risk of strokes you were at
13:06greater risks of getting her attacks in Japan the Japanese Society of Cardiology
13:15said that everybody with a cholesterol over 220 should get a statin so this is
13:2141,000 patients who are on statins and as they take statins their cholesterol
13:27levels are reducing so you would expect that if your cholesterol level is comingDo statins prevent diabetes
13:32down you should be at lower risk of dying but as you can see on the graph the lower your cholesterol
13:40greater the risk of all-cause matter mortality the greater the risks of
13:45cancers the greater the risks of strokes how does that make sense now in that
13:52same study we evaluated the number of diabetics so you would think that if
13:59statins are good for you as you reduce the cholesterol you should have a lower
14:04incidence of diabetes but as you can see as the cholesterol got reduced by the
14:09use of simvastatin that was the group that had the highest risk of being a
14:15diabetic now we said that the cholesterol intermediates are involved
14:22in preventing oxidative injury because the parental intermediates take the
14:30protein manufacturing machinery that we have and creates L&O proteins that
14:37prevent oxidative damage they also make some DNA repair enzymes that prevents
14:44injury to ourselves so that we don’t get cancers so this is the function of the
14:50cholesterol intermediates so again theDo statins prevent cancer
14:56deception from the statin industry and the statin experts is that let’s go on
15:03offense and say that statin use is associated with a reduced chance of
15:09having mortality if you have cancers so they took a Danish population 40 years
15:16in order all of them had cancers and they’re comparing people who are known on statins to people who are on statins
15:23again this is an unfair comparison the reason is that if you have high
15:30cholesterol and you have cancers you have a better chance of survival and you
15:35would give cholesterol reducing medicines only to somebody who has high cholesterol not to somebody who has low
15:42cholesterol so similarly the comparison should be that somebody on low-dose
15:49middle those and high dose if cholesterol is beneficial in preventing them from dying
15:57the higher the cholesterol the lower should the higher the statin dose the
16:03lower should be your mortality but not so in this study if you were on the
16:08highest dose of cholesterol you had a much greater chance of all-cause
16:14mortality and also of cancer mortality compared to the low-dose cholesterol
16:21group now this is a study done in patients 65 years and older called an
16:29older population and I looked at that and I said what do you mean 65 is old
16:37but anyway there were 3,000 patients in each group the pravastatin used reduced
16:42cholesterol by roughly 33 percent they were followed for three years what
16:48happened the people on pravastatin had 50 more cancers approximately it was statistically significant so Jeff showedDo statins prevent calcium buildup
16:59his slide of having calcium in his led I’m sorry he doesn’t have calcium in the
17:05led somebody else does he has a zero calcium score and the cholesterol
17:12converts vitamin K 1 to K to the prelate proneural intermediates and they
17:18activate an enzyme that prevents calcium deposition in the blood vessels of the heart so this is a VA study and the VA
17:27study was done in patients who were on statins not using frequently versus
17:32those who were using frequently when you see the people who are using statins a
17:38lot they had more calcification when they were followed at 4.3 years the
17:45progression of calcium was highest in the people using statins compared to the people who were not so for the sake ofDo statins kill smooth muscle cells
17:55time I’m skipping some slides they are on my Twitter feed this is another
18:00compelling information you take smooth muscle cells these are cells that line the wall of the vessel
18:06and you grow them in a culture dish and you give them increasing amounts of the
18:14statin drug and what you’re finding on the slide to the left of the screen here
18:21is that as the dose of statin increased more cells were dying now a picture is
18:28worth a thousand words and in this picture the arrows are pointing to the effects of statins that are killing the
18:34smooth muscle cells now I wanted to makeDo statins reduce LDL
18:39sure that I have a few slides that showed animation so that you know that I
18:45can make good slides so here is a cell
18:50that is undergoing repair and as it undergoes repair it puts cholesterol out into the milieu the HDL which looks
18:56discoid in the beginning is there to pick up the cholesterol it becomes spherical and then it does this amazing
19:03thing it transfers the cholesterol from HDL to LDL the LDL takes the cholesterol
19:09it is then subsequently removed by the liver through the LDL receptor and the
19:16liver recycles the cholesterol and the protein this is an important biological
19:24but if you prevent that transfer which is happening through the C type enzyme
19:29you create something that medical profession medical professionals like a
19:34lot you are increasing your HDL you are reducing your LDL so that’s what
19:43happened in this study so this is an illuminate trial about seven and a half thousand patients in each group the
19:50group to the left the HDL which is the good cholesterol is very high 83 the LDL
19:57is very low a cardiologist like me would salivate over this say this is so good
20:03why are you even coming to see me you don’t need to come see me because you’re gonna live forever what happened in this
20:11study with high HDL and lowered DL
20:16people died more people had cancer mortality more were hospitalized for
20:21heart failure more had infections and more had strokes so this is where I wantIndustry sponsored clinical trials
20:29to tell you how an industry-sponsored clinical trial is done
20:3595% of studies that are done on statins are sponsored by the clinic by the
20:40industry and the industry plays the clinical side which is at the top of the slide about 400 sites in about 25
20:47countries is a blockbuster study physicians like me at the side are paid by the industry the industry hires a
20:55team of experts called CAC central adjudicating committee they are
21:00paid by the pharmaceutical industry they hire a DSM a data safety and monitoring
21:06committee that’s designed to protect the patient who pays them it’s the
21:12pharmaceutical industry the FDA which is to approve new drugs a substantial
21:20portion of their budget comes from the pharmaceutical industry there’s a revolving door between pharmaceutical
21:26industry and FDA you would think that medical journals that take these blockbuster studies that are going to
21:32make mega profit for the industry are they conflicted yes they are because
21:39when a blockbuster study is published millions of reprints are ordered that is
21:45extremely beneficial for the statin industry and for the medical journals
21:52you would think that American Heart Association and ACC are not conflicted but just go to one of their meeting and
21:59see the dominance of the industry a large portion of their budget comes from them you would think that physicians
22:06like me are not conflicted but they’ll come and say doctorally we think that
22:13you are a pretty good opinion leader in your community you can speak why don’t
22:19we give you about three thousand dollars five nights a month and why don’t you go and tell your friends and your community
22:25that this is a good drug use it I urge you to go to ProPublica calm put the names of the physicians you
22:32will be shocked to see that some physicians are earning between a hundred to five hundred thousand dollars a year
22:39speaking for the industry and promoting their drugs so let’s say that theEthical doctors
22:47pharmacy pharmaceutical industry the doctors who have done the study are completely ethical they’re aboveboard
22:53they have done nothing wrong that the data is robust and you say come and show
23:00me the best study you have done that shows that statin is beneficial you got to go back to 1994 the Forrest trial
23:07about 4,000 plus patients in Scandinavia half of them given simvastatin half of
23:14them not given similar a turn at the end of five years the reduction in mortality
23:20was 0.6 percent per year that is the most robust endpoint mortality zero
23:27point six percent per year okay now itMalcolm Kendrick
23:33would be honorable for the doctors and the pharmaceutical industry to say yes
23:40this is a result but they pointed saying that there was a 42 percent reduction in
23:45mortality now I borrowed these slides from Malcolm Kendrick I’ve used them before I would
23:51appreciate that even if you have heard it before that you laugh let’s say the
23:57Colorado lotto if you buy a ticket the chance of winning is one in fifteen
24:02million and I come and say I’m an expert at predicting who will win I’ll increase
24:09your chances by winning by 50 percent how much is that realistically that is one point five and fifteen million so in
24:18absolute terms that is 0.6 zeroes three
24:23so if I were a pharmaceutical industry I would sell my wares like this do you want to be a millionaire send me 50
24:30bucks I will increase your chances by 50% this is no contract on the other
24:37hand if I were being honest this is what I would say that the pathetic desperate lonely doctorally can very
24:46minuscule II increase your chances of winning the Lord Oakley send me this much money you get the point so the
24:55truth is that you should always talk about absolute risk reduction never
25:01relative risk reduction so I don’t want you to get bogged on by the slide I took
25:06a lot of time to prepare it and it has very useful information so in the LDL
25:12reduction line or showing the degree of reduction in LDL over time from 1994 to
25:182017 and on the Bott hallory benefit
25:23line is showing the degree of mortality benefit so the forest trial we’ve seen
25:29over five years three point three percent reduction but then 2004 was a
25:34landmark point in which the why ox trial came out when the why ox trial was
25:41evaluated it was found that Merck did data tampering the same company that did
25:46the forest study they also found that Merck had the data that showed that
25:53these people were having heart attacks what happened 88,000 patients had a
25:59heart attack roughly 40,000 patients died and when it came to light Merck paid five billion dollars in damages
26:08that’s the first time that Congress put in guidelines that said that if you do a
26:15study you need to publish it because before that a company could do ten different studies hidden hide the nine
26:23and publish the one that showed benefit now that’s when scrutiny started and if
26:29you look at the trial called the cards trial in diabetics thirty three percent
26:35reduction in cholesterol 1.5 percent reduction in mortality but that was
26:41before the clinical trial guidelines a similar trial was conducted right after clinical trial guidelines same group of
26:48diabetic patients similar reduction in collected cholesterol zero reduction in mortality the Jupiter
26:57trial this trial reduced cholesterol by over 50% the reduction in mortality was
27:05half a percent the fourier trial that I will show you reduce cholesterol by
27:10almost 60% it had 28,000 patients there
27:17was a slight increase in mortality so how did the mortality benefit miraculously disappear so I’m an Indian
27:27and I get very compassionate and when I get like that I talk very fast so I find
27:33that actually I have five more minutes so this is telling you what pcsk9 does
27:41and I don’t know if they’re doctors in this audience so I want to go over that the pcsk9 comes in and tells the body
27:48that something is happening let’s down regulate the LDL receptor so let’s
27:54remove the LDL receptor from the liver so that more LDL is there in the circulation why is it doing that it’s an
28:01acute phase reactants in other words if you have an infection pcsk9 goes up the
28:07LDL is there as we have seen to fight infections to modulate inflammation to
28:14do cell repair and in a time of need provide energy but for whatever reason
28:22the people want to use pcsk9 inhibitor to remove the pcsk9 and as the pcsk9 has
28:29removed the LDL receptor is present on the liver and it mops up and takes away
28:36all the LDL so the LDL levels go very low with pcsk9 and with low LDL number
28:44perhaps all the beneficial effects of what LDL is doing also go away I refusedPCSK9 study
28:52to call LDL the bad cholesterol so what happened in this study this is the study
28:58on pcsk9 in 28,000 patients they dropped the LDL cholesterol to 30 milligrams per
29:04deciliter what they were more deaths in the group that
29:10got the pcsk9 I would think that this is
29:15what you should say that John Abrahamson said dying of correct corrected cholesterol is not a
29:22successful outcome pcsk9 was designed when humans were going through a
29:29nutrient depleted environment we had unpredictable fasting it was designed so
29:34that you would have the ability to fight infections that your body can be provided with energy it also has many
29:42other functions that I will not get into so the Big Pharma the food industry near
29:50hundred percent of cardiologists the american heart are telling us eat a processed vegan diet take statins take
29:57pcsk9 inhibitors they want to wipe the LDL and the pcsk9 out of our bodies
30:05should we do that and I’m using a nice tagline from dr. Mercola because he says
30:11take control of your health do your own critical thinking so when I prescribed aInformed consent
30:20statin I think that I need to discuss with the patient the risks and benefits that’s informed consent because should i
30:29view startings as might record mitochondrial toxins something that affect memory and cognition that cause
30:35vascular calcification that caused insulin resistance that from more oxidative injury that damage your
30:42muscles that most of the trials that have been done are conflicted by
30:48industry interest so I’m gonna use thisabdicated responsibilities
30:54and the next as my last slide and I think that as a physician I have a right
30:59to say this I think that physicians have abdicated their clinical
31:05responsibilities to their patients they are looking to key opinion leaders big
31:11pharma food industry various medical societies and they are failing to talk
31:18to their patients they seize their clinical thinking abilities so I think we should accept some
31:27responsibility that this is right that we are probably the first or the second
31:33leasing leading cause of death in the US and worldwide thank you [Applause]
31:39[Music]
