A Mysterious Figure
While studying the lipid system in depth, lipoprotein(a) (pronounced lipoprotein little a; also called Lp(a)) was a particle that repeatedly came up in the study material in passing, although at the time I had no idea what it was. It was never something I had seen mentioned in the mainstream information on lipids, but the more I read about it the more I started to get the suspicion that lipoprotein(a) wasn’t exactly like other lipoproteins, like LDL and HDL. The general structure was the same as other lipoproteins – with a phospholipid “shell”, cholesterol being carried as its “cargo”, and proteins attached to the shell (called apolipoproteins) that allowed it to carry out certain functions. But, the research often described lipoprotein(a) as mysterious, or an enigma, and oft repeated was that its function was still largely unknown. At the same time, it was stated that it was an important risk factor for heart disease, and many papers discussed possible ways to lower it. I was left wondering if lipoprotein(a) was really just a particularly deadly particle causing damage wherever it went, or if there could be more to the story.
A Lipoprotein With a Tail
Lipoprotein(a) is a low density lipoprotein that is found in humans, old world apes, and the hedgehog.1 Lipoprotein(a), like LDL, contains a protein called apolipoprotein B (apoB) and Lp(a) is often described as “LDL-like”. This is because the structure of lipoprotein(a) is very similar to LDL, but with one addition. Attached to the apoB there is another protein – apolipoprotein(a). Like other apolipoproteins, apo(a) is what allows Lp(a) to carry out different functions, but the structure of apolipoprotein(a) is vastly different from other apolipoprotein structures I had seen.
Instead of being incorporated into the shell of the lipoprotein as others are, it is instead attached to apoB at one end and wraps around Lp(a) like a long tail.2 Apo(a) also comes in different sizes, and its size is determined by genetic factors, based on how many copies of a protein (called a kringle) it has. The size of apo(a) is one of the determining factors for levels of lipoprotein(a) in the blood: the larger the apo(a) form (the longer the ‘tail’), the lower the genetic baseline of Lp(a), and likewise the shorter the ‘tail’, the higher the baseline Lp(a).
Risky Business
Beyond studies focusing on Lp(a) metabolism, structure, and function, many studies I saw were centered around lipoprotein(a) as a risk factor for heart disease. This is because people with cardiovascular disease typically have higher levels of lipoprotein(a)3, lipoprotein(a) appears to have some moderate predictive outcomes when it comes to cardiovascular disease4, and some studies show that having higher genetic levels of lipoprotein(a) is associated with increased risk, as well5 – although associated doesn’t necessarily mean causal. But, is the big picture so uncomplicated that lipoprotein(a) can be painted as a “risk” that we’re better off having as low as possible, as early as possible? The answer to this is quickly complicated if one looks at lipoprotein(a)’s association with all-cause mortality, cancer mortality, and risk for brain and airway bleeding as low levels are correlated to higher risk for all of them.6, 7 While genetic baselines do contribute a large deal to lipoprotein(a) levels in the blood, it isn’t the only factor involved.
Beyond Genes
Beyond genetic levels lies more clues…
Dietary changes, specifically low fat high carbohydrate diets can raise lipoprotein(a)8, and different protein sources can also impact levels.9 Additionally, Insulin-Like Growth Factor (IGF-1) lowers lipoprotein(a), although the mechanism isn’t known and may involve either increased clearance, or decreased production.10, 11 I found it quite interesting, as well, that interleukin-6 (IL-6; a protein used for inflammatory signalling) raises lipoprotein(a) levels in vitro12 which is likewise reflected in human models where the IL-6 receptor is blocked with drug therapy resulting in lower lipoprotein(a) levels.13 This fit with the speculation that lipoprotein(a) is an acute phase reactant similar to hs-CRP. In other words, lipoprotein(a) may go up from certain types of inflammation caused by damage or infection elsewhere in the body.
There is in fact some evidence for this, as seen in in vitro experiments14 and studies looking at patients during the acute phase response compared to controls.15 Higher levels of lipoprotein(a) are also found in those with conditions related to inflammation, such as lupus16 and rheumatoid arthritis17 although this may also be partially genetic.18 This role as an acute phase reactant – levels rising in response to specific inflammatory signalling – could partially explain why it is correlated with heart disease risk beyond genetically determined levels, as atherosclerosis is tied to inflammation and damage in the arteries as well.
Graph Source: doi:10.1161/ATVBAHA.107.145805
Lp(a) vs. Lp-Pla2
One way to separate the risk of lipoprotein(a) alone from its increased level during inflammatory states is to control for a risk factor that would indicate damage that might increase inflammation (and lipoprotein(a) by proxy) – such as oxidative damage. One study compared lipoprotein(a) levels with levels of Lipoprotein-Associated Phospholipase 2 (Lp-pla2). Lp-pla2 interacts with oxidized fats found on the phospholipid shells of lipoproteins when they’re damaged, removing them in order to protect the lipoprotein from further damage caused by oxidative byproducts. In this way, Lp-pla2 has antioxidant and protective functions, and high levels of lp-pla2 activity would be indicative of high levels of oxidative damage.19
When comparing people with high or low levels of lipoprotein(a) compared to high or low levels of lp-pla2, in those with high lipoprotein(a) but low levels of lp-pla2 the hazard ratio for increased cardiovascular risk was only 1.1 (that would be a 10% comparative increase, not especially significant). This was the same risk as having lipoprotein(a) in the lowest group but a mid-range level of lp-pla2. Meanwhile, those with high lipoprotein(a) and high lp-pla2 had a hazard ratio of 3.5, a 350% relative increase.20 In other words, if lipoprotein(a) was high, but signs of oxidative damage were low, so was risk for heart disease.
More Than Just a Marker
Beyond all the talk about hazard ratios, and risk, and all-cause mortality, though, there was one question that persisted while studying lipoprotein(a): What is it for? The other lipoproteins had clear uses outlined for distributing energy, or cellular repair, or managing immune reactions, but lipoprotein(a)’s use in the system remained elusive and poorly defined. It didn’t appear to transport energy, and although it was similar to LDL in shape, it has a lower affinity for the LDL receptor21, and thus likely couldn’t be used primarily by cells for repair via traditional means, either. Luckily, there have been a few possible hints about its use in the system, beyond as just a marker for risk.
For one, the structure of lipoprotein(a)’s “tail” – apo(a) – is similar to plasminogen22, which is used during injury repair. When an injury occurs, for example in an artery, platelet accumulation occurs and a protein called fibrin acts like a glue to bind it together, forming a scab-like structure over the wound to prevent bleeding.23 This scab is not just a bandage over a wound, but is actively involved in the healing process and is constantly changing through progression of the repair. One of these changes is mediated through plasminogen binding to fibrin, to break apart the “glue” (fibrin) holding the scab together in order to maintain proper structure, and ensure thrombosis does not occur. This dissolution process of plasminogen is called fibrinolysis.24
Balancing the Scales
Lp(a), along with plasminogen, may help maintain balance between clot production and dissolution.
Apo(a) appears to bind competitively to fibrin over plasminogen, blocking the fibrinolysis effects of plasminogen, and thus may contribute to decreased clot dissolution25, although this same mechanism may be useful in maintaining homeostasis during wound healing. Just like plasminogen and fibrin, lipoprotein(a) is found in healing tissue, but not in healthy tissue, at the same sites that fibrin is located, especially on the surface of the fibrous cap. It is speculated that lipoprotein(a) helps prevent excess fibrinolysis, which would result in bleeding and impaired repair, on the outside surface of the clot in order to aid with injury resolution.26 This use in clot strengthening, and inhibiting clot dissolution, through binding to fibrin may explain why higher levels of lipoprotein(a) are associated with lower levels of death related to brain and airway bleeding, as well, as increased fibrinolysis during a major bleeding event could be detrimental in terms of mortality outcomes.
Carrying a Heavy Burden
Beyond its involvement in wound repair, I discovered that lipoprotein(a) also has a few other key features. For one, it appears to be involved in the immune system similar to other lipoproteins. Infection by Hepatitis C, for example, is inhibited via interaction with apolipoprotein(a) and this inhibition is proportional to the apo(a) size. In other words, the longer tails did a better job at inhibiting infection in vitro.27 The extent of lipoprotein(a)’s involvement in the immune system is likely still largely unknown, but this interaction does provide one example of the possibilities that may be uncovered in the future.
Viruses aren’t the only thing to attach themselves to apo(a), though. One of lipoprotein(a)’s most interesting aspects is its role as a preferential carrier for oxidized phospholipids. As discussed previously, phospholipids are what the membrane of cells are made of. When cells, or lipoproteins, become damaged they release these oxidized phospholipids (oxPL) to prevent further injury. What happens to these oxidized phospholipids? If Lp(a) is present, they preferentially accumulate on and bind to apo(a).28
OxLDL By Another Name…
Because lipoproteins can transfer their oxPL to Lp(a), or more accurately that they remove oxPL from their shell and Lp(a) picks it up, the levels of oxLDL and Lp(a) are very similar – almost the same.29 It isn’t that Lp(a) is the only lipoprotein to become oxidized, in fact it isn’t Lp(a) itself being oxidized that’s being picked up by these tests, but rather that apo(a) is carrying oxPL originating from other particles. There is a possibility that Lp(a) plays a role in the innate immune system, and picks up this oxPL in order to detoxify it, and further transfers byproducts from this process to other carriers to remove it from the system entirely. However, if oxidative stress is too high, the capacity of Lp(a) to handle this role may be impaired, and thus lead to increased risk of heart disease – hence why high Lp-pla2 activity modifies risk as it may be a marker of how much “workload” that Lp(a) has.30 This role as a detoxifier may also explain why, referring back to the Lp-pla2 paper, when comparing cardiovascular outcomes between those with no Lp(a) (and thus no oxLDL) and those in the next lowest quintile, the risk doubles. Peter of Hyperlipid has also speculated that the package of oxPL, carried by lipoprotein(a), may be useful in inducing apoptosis in cancer cells, and there is some evidence showing apo(a) inhibits tumor growth.31, 32
Riddle Wrapped in Mystery
There are no shortcuts to finding answers, or solving puzzles
To be sure, there is much we do not know about lipoprotein(a). Not only as far as risk in general, but also if it’s the lipoprotein(a) in itself that contributes to risk or if the context matters. We do have some hints, seemingly pointing towards context being key, and at the very least it seems that it is high lipoprotein(a) at a later stage of disease that may be influencing risk, as lipoprotein(a) isn’t associated with early thickening of the arteries, which contradicts the common idea that lipoprotein(a) is harmful to the arteries in itself.33 In addition, it appears that the oxidized phospholipid content contained on apo(a) is highly important when associated with extent of disease progression34, with one study stating that oxPL may “significantly contribute or primarily account for” the risk associated with lipoprotein(a) (emphasis mine).
Another question left unanswered is how much population based risk calculating studies are influenced by those with familial hypercholesterolemia as they also tend to have higher levels of lipoprotein(a) and are already at higher risk of developing cardiovascular disease and dying early.35 While the argument is made that this risk is from lipoprotein(a) or high cholesterol levels in general, it may also be that the difference in LDL receptor efficiency may also result in delayed or inefficient healing from arterial damage36 and thus higher need for the reparative aspects of lipoprotein(a). It is notable that in French centenarians, high lipoprotein(a) levels were quite prevalent37, and that in elderly populations there was no correlation between lipoprotein(a) levels and all-cause mortality in men38 – perhaps because of the lower concentration of those with familial hypercholesterolemia in elderly groups.
Beyond risk, there is much to learn about the functional role of lipoprotein(a), as well, and as study of it is far younger than the other lipoproteins we may have a long wait before we can shed light on what other influences it has, what other roles it may play, and what other mysteries it may contain. I am sure I will revisit lipoprotein(a) as we continue to learn about it, and I look forward to unraveling the mystery of such a unique lipoprotein. Until then, you can check out this quick recap to sum up lipoprotein(a) and context of risk in under 10 minutes in the short talk I did at Low Carb Breckenridge 2018:
Sources
I read the article and watched the video. As someone with high Lp(a) eating a keto diet, somewhat your comforting research summary about this particular marker is very welcome. Thanks Siobhan!
For those with high Lp(a), do you recommend measuring exotic markers like Lp-pla2 or are tests like coronary artery calcium scans and carotid intima-media thickness tests typically sufficient to diagnose heart disease?
For me personally, I intend to get Lp-pla2 tested on Friday just to see where it’s at. I’m not sure how reliable the test is, and of course the over all big picture is far more important to me than any one marker, but I would like to know what it is. Of course CIMT and CAC is also on my list, and I consider those the preferred measures, since they’re measuring actual extent/progression of the disease instead of markers we don’t fully understand yet.
So, for myself, both.
I too have long term elevation of Lp(a) but it varies spontaneously from 100 to 200 m mole/L. I have near optimal diet and lifestyle but am 75 years of age and male. My CAC score 3 years ago was 250 prior to Keto diet, 2 years ago 220 and this year suddenly reversed and went up to 290. This after 1 year of a carnivore diet to treat a GI issue. However other lab markers did not change significantly including LpPla2. A CT angiogram demonstrated not only the 2 calcified lesions seen on CAC but one significant non calcified plaque. The concern is that my Lp(a) is the inciting factor and are considering a PCSK9i. I know carnitine is supposed to lower Lp(a) but during this last year it has remained near 100.Thoughts on carnivore diet and its possible impact on atheroma formation?
Hi – beyond speculation based on traditional carnivorous diets (e.g. maasai, inuit, some others) who generally present with low rates of MI, I don’t think we have a lot of data on a carnivorous diet and atherosclerosis.
Regarding your scores – was each one done at the same facility, with the same machine and technician? I have heard from some people that using different machines can result in a somewhat larger error rate than using the same machine/etc for each test.
I can’t really comment on whether you should take a medication or not, as I’m not a doctor. As with LDL levels, we each have to read the research and decide what makes us most comfortable longterm. You may want to also discuss in the CholesterolCode facebook group, as there are people there who may be able to comment further as well.
FWIW, although I haven’t published the data yet, I have personally found that my lp(a) also goes down on a higher fat (KetoAF – 2:1 fat:protein by macronutrient gram) carnivorous diet, but I’ve not seen this replicated in anyone else yet so I don’t know if it’s true for everyone.
Out of curiosity – when your lp(a) has fluctuated did your diet change at all when it was higher/lower? E.g. higher or lower fat, different diet composition, etc. I’ve not found mine to fluctuate randomly, but it usually relates to what I’m eating, or other events like illness, etc.
Try this for 4 weeks:
Vegetarian diet (no meat, no eggs)
Niacin (500 mg twice a day)
3-4 grams Omega 3 per day
I reduced my Lp(a) from 55 to 19 mg/dl.
I’m not sure you have to do this. My lp(a) on the mg/dl scale is 150 (three times your starting value), yet I had a zero score on CAC after 5.5 years keto/low carb.
Very good information. A note about those with FH: although they are known for developing heart disease earlier, their overall death rate is about the same as a normal person. They tend to get other diseases less. There’s a hypothesis that this occurs because there’s a link between “cholesterol” and the immune system. For instance, FH people get less cancer.
I have “high” LP(a), but low HS-CRP.
For another take on LP(a):
https://drmalcolmkendrick.org/2017/01/16/what-causes-heart-disease-part-xxiv/
I tried taking Vitamin C (as suggested by the link) to see whether my LP(a) would go down…but Vitamin C made me feel, well, strange. So I ceased taking it. I’m not sure if there is an effect from Vitamin C, but as you point out, there’s not a lot of data indicating reducing LP(a) is beneficial (or detrimental). So, I’ve chosen to let my “high” LP(a) slide. I assume that losing 50+ pounds and feeling great, using a near zero-carb/carnivore diet an intermittent fasting, hopefully means LP(a) is meaningless.
Oh, yes, FH and general mortality is something I’ve had quite a few discussions about with Dave and others, I was just sticking to addressing the heart disease side of things specifically in this article for the sake of staying on topic. I’d definitely agree that cholesterol (more specifically lipoproteins) are involved in the immune system – it’s acknowledged occasionally in the official literature that they are. As for cancer, I have some theories as to why that would be, as well, and yes it ties back to cholesterol/lipoproteins.
I’ll address the lipid system’s involvement in the immune system at some point, it’s a bit of a pet topic of mine. It’s really fascinating stuff.
As for vit C and lp(a) I’ve seen some theorizing that lp(a) was developed because we can’t synthesize vit C anymore, but I’m not sure how true that is, after spending a lot of time looking into it. Perhaps it’s related, but there are other animals that can’t synthesize vit C and did not develop lp(a), and likewise ones that developed lp(a) that can still synthesize vit C. It may be a coincidence. It’s also mentioned in the link that high need for lp(a) might be due subclinical scurvy, as he showed that when he made guinea pigs develop scurvy and gave them lp(a) the lp(a) integrated into the arteries…. but I think that may just be a demonstration of lp(a) doing what it normally does (helping with general tissue repair) not scurvy in particular. There’s also a study floating around demonstrating vit C supplementation does not lower lp(a) levels. I think the larger picture is that high need for lp(a) is likely caused by damage to the arteries in general, or high levels of oxidative stress, perhaps other things we’re not aware of yet – which coincidentally vitamin C deficiency contributes to. I don’t think that means vitamin C hypersupplementation is the “cure”, or even at all protective for lp(a) related problems (if there are any), though. It just hasn’t really done much to convince me at this point.
It’s a rabbithole I fell down a while ago, but I came out with the impression it might be an oversimplification of things.
I also have what’s considered “high” Lp(a) (it’s about three times higher than my sister’s, too!) I’ve decided to look further into it to see if it’s somehow diet related (I’m also carnivore and eat primarily pork and poultry), and if I can’t find anything I’ll still be getting a CAC and regular CIMTs and see what happens. With the info we have now, it would be all I’d be comfortable doing, really.
I have tried various ways to reduce my high Lp(a):
1. Lost 6 kgs (from 72 kg to 65 kg) – No effect on Lp(a)
2. Tried meat heavy diet and low carbs for 3 months – My Lp(a) jumped from 35 to 55 mg/dl
3. Tried Lysine, Vit C & Proline for 1 year with daily meat consumption – no effect on Lp (a)
4. Tried vegetarian diet, 3-4 g Omega 3 and 500 mg niacin daily for 40 days – Lp(a) dropped to 19 mg/dl. Non-veg meal once/twice a week is also fine while trying this regimen.
Hi Siobhan,
I found out yesterday from an NHS cardiologist that I have a very high LP(a) count. She said I needed to stop my LCHF diet right away or go onto statins to lower my LDL.
She said it was really dangerous to have LP(a) but then discharged my from the service as I didn’t want to take statins.
Does anyone know of any experts in the UK that understand this stuff?
I feel like I need to get a medical degree to find out what I should be eating.
Not sure about anyone in the UK, that could be helpful (I don’t know much of anyone who specializes in Lp(a) specifically) but the reaction to come *off* of a LCHF diet seems odd to me, considering higher carb/lower fat diets *raise* Lp(a).
As for high Lp(a) in general, I have high levels as well. I am getting Lp-pla2 tested today, but I also intend to get a CIMT done at my next appointment (this check’s for arterial thickening). I also try to look at the big picture – what’s my insulin level? What’s my HDL and triglycerides? What’s my CRP?
From what I’ve seen the risk for Lp(a) is pretty context dependent, and even in the research they say it’s only a moderate risk factor (especially, in my opinion, compared to insulin resistance). Perhaps looking at your big picture would help you figure out what you want to do as well?
Hi Siobhan,
Thank you for replying to my comment. I have been reading and also watching youtube videos like crazy over the last few days trying to find my feet.
I was speaking to a radiographer friend of mine who said that I could get may cerotic artery scanned using ultrasound to see if there was any plack there. I think that is the CIMT you are talking about.
Your comments are really useful. The idea of looking at the whole picture was reassuring.
After 18 months of LCHF (generally in ketosis) I started with tryglicireids of 1.42 which are now down to 0.58, HDL of 0.95 now up at 1.56 – all good. I think the cardiologist was suggesting statins as my LDL started at 1.80 and is now at 5.18 and it climbs every time a get a new test.
When you say about looking at the big picture, I was planning on trying to get a CIMT scan, perhaps a calcium scoring CT scan for my heart. As I understand it both of these are looking at actual calcium build up as opposed to markers or proxy measures for vascular health.
I will try to get my Lp-pla2 tested as well. Can I ask if there are any other tests that you think might be helpful for me to build the bigger picture of my actual vascular health and risk? Are there tests for inflation for example?
Yep, CIMT is an ultrasound looking at the Carotid Intima-Media Thickness, which is what you’re talking about. I personally like it (and intend to get it done), because arterial thickening is one of the first physical symptoms of developing atherosclerosis, even before hard plaque formation, and the ultrasound doesn’t pack as much radiation as something like a coronary artery calcium scan so you can re-test pretty frequently (I intend to do every 6 months if possible).
Yep – I’d agree on the HDL and trigs, I generally like to see trigs go down and HDL up, which is exactly what happened for you.
I’m not surprised at the reaction from the doctor in regards to LDL, but as you likely know my view on it is a bit different. Plus, if you’re following a high fat, low carb diet LDL may go up for a benign reason (transporting fat based energy) which may not present the same risk as LDL going up due to inflammation, for example. I’m not sure if you’ve seen it yet, but you may be interested in Dave’s Breckenridge talk, which discusses high LDL in a LCHF context.
At one points statins were also offered to me by a previous doctor, and I did my own research on them and made my own decision (I personally decided not to), in general doing your own research on it could not be a bad thing, and it can help you decide if that’s what you want to, especially in regards to statins and primary prevention. It’s ultimately your choice.
CIMT and CAC are both things I’d likely do in your position (actually, I sort of am in your position, with “high” Lp(a), and high LDL, and I do have these on my to-do list) I think both are good for actually looking at physical signs of the disease, instead of proxies. Along with that, I also meant looking at current blood markers together – HDL, TG (which you’ve already mentioned), fasting insulin, hs-CRP (an inflammation marker), HOMA-IR (a measure of insulin resistance), etc
Insulin resistance in particular is tied in to heart disease risk (Ivor Cummins discusses this quite a lot) particularly well, so I try to get insulin on all of my bloodwork, but if you can’t TG:HDL ratios are next best in my opinion as the ratio (barring genetic factors) seems to reflect level of insulin resistance.
I listed my preferred ones above (HDL, TG, insulin, hs-CRP, HOMA-IR), hs-CRP is an inflammation marker but it’s worth noting that hypertriglyceridemia (high triglycerides) also appear to be part of the acute phase response (response to inflammation), and HDL is tied into TG levels, and insulin appears to be involved as well. Because they all “fit” together as an over all system, that’s why I mention “the big picture” – all the markers together paint a picture of how things are functioning inside.
Hi Siobhan,
Thanks for your detailed response – I really appreciate your time and effort.
I have set up an ongoing payment to help keep you all going.
Cheers
Andrew
No problem at all Andrew! While it is my job, I agreed to take on studying and working on this full time because above all I want to help people, in any way I can.
Thank you so much for your support, as well! We really do appreciate it, and we intend to continue as long as we can 🙂
Except I have clear/no plaque CIMT so carotid looks great, but I have symptomatic disease in my LAD. Ivor Cummins and Jeffrey Gerber discuss this in a recent video, and agree that CIMT does NOT necessarily correlate with CAD. I’m getting a CAC next week. I want to go next for that 640 slice CT scan, I’d like to know just how close it can get for magnification. And, do you or Dave know anything about the current state of MRI of heart for measuring plaque, soft or hard, or IMT?
Interesting! Yes I saw that recently as well. It’s why I like getting both – CAC for long term checkins and CIMT for shorter term trends. CIMT is certainly not perfect and I would not want to rely on it alone. For what it’s worth since that comment I’ve had CIMT, CAC, and carotid doppler. I try not to go with just one measurement. 🙂
As for the MRI question, I’m not sure off the top of my head, but I’ll check with Dave and see if he knows.
What was your CAC score out of curiosity?
I have the same levels of Lpa as you so im just curious.
It was 0, no calcification noted on the scan. But, I was only in my early 20s at the time so I’d have been astounded if the result had been anything else. It was not done to form conclusions, only to get a baseline so I can check back later (in another 2 years).
Hi Victoria — I don’t know that information with regard to MRI. The CIMT is often used as a proxy for atherogenic burden, but it’s not perfect by any means. I most liked the 640 slice for overall accuracy, however, it’s very expensive and I had to fly to NY for it. 😉
Hey Andrew. Pretty much in the same boat. I don’t have the exact numbers on hand, but same pattern as yours. Have higher HDL, lower triglycerides, since starting LCHF/Keto. But also high LDL, around 200 mg/dl. Not had my LP(a) measured.
Since seeing Dave’s work, I realized (after the fact) that I’d gone into both my last 2 blood tests unconsciously restricting eating in order to “be good” ahead of the test. It was only after seeing Dave’s work that I realized restricted eating ahead of the blood lipid test would raise my LDL numbers. Do you think you might have had the same issue?
I fully intend to pig out for a week on LCHF foods before my next test to see if my LDL comes down.
Also my doctor gave me the fright of my life after my first cholesterol test came back after starting LCHF. It was only afterwards that I realized how much more important the 3 cholesterol ratios were compared to an LDL score on its own. Long story short, my ratios were fantastic due to high HDL and low triglycerides. A year later they’d improved by around 50%, even though the LDL stayed unmoved at 200.
Hi Arsalan,
I don’t think I had been eating any differently in the time leading up to my last blood test. However, I will look at Dave’s protocol in more detail. Perhaps I will try it out and see if it affects my LDL.
Hi Andrew,
My Father was told last year about his very high LP(a) count after going to see a private doctor. The doctor said that all his children should be tested and I found out yesterday that I also have high levels. I received my blood results from a doctor on the NHS, however he said that there was no way he could give me any information on this as he didn’t know anything about it.
Unfortunately the UK still has no idea about this, but it is becoming a bigger deal in the US now with current clinical trials being done out there. Diet and exercise unfortunately does not affect the levels, but moving to a more plant based diet will greatly reduce your cholesterol (which is the only thing we can control).
I would really suggest going on statins though as this has really helped my Dad, heart disease runs in our family so we have taken this news very seriously. I am only 23 and a vegetarian so hope to keep my cholesterol under control!!
Just a note – it may be worth looking at my posts on my Feldman Protocol attempt, and on my side of the Tandem Drop experiment. You may be interested in my lp(a) levels over the course of both experiments. This data seems to contradict the idea that lp(a) isn’t influenced by diet. I’ve likewise seen my levels change (twice now) when switching from a pork based to ruminant (beef) based diet as well.
It’s also worth noting that some studies indicate (one of which is listed in this post) that risk from lp(a) is context dependent. Ivor Cummins also tipped me off to another indicating lp(a) levels are likewise dependent on HDL levels, e.g. if HDL is high (signalling low inflammation etc) risk is low. This is not a guarantee, but interesting regardless.
And a last note is that statins have been shown to increase lp(a) somewhat. Not discouraging (or encouraging) their use, but worth noting imo.
Thanks Siobhan for the information. I have moderately high Lp(a) at 40. The cross marker correlation with Lp-PLA2 is reassuring.
I was recently trying to figure out more about Lp-PLA2. I seem to be at the high end of the normal range (179). I ran across this paper:
https://www.semanticscholar.org/paper/Lipoprotein%E2%80%90Associated-Phospholipase-A2-Activity-Is-Wallentin-Held/06b17da0908817b9735252fbdf6d91ac6fe30478
which reenforces what you have spoken about. It does not call out Lp(a), but shows that people with CVD need to be in the highest quartile of the measured range of Lp-PLA2 to significantly increase risk. I would imagine that people below the level of damage of diagnosed CVD would be even safer.
I’m supposed to have a CIMT soon. I *think* this would show if anything bad is taking place.
It sure would be nice if these lipoprotein risk studies could start measuring insulin sensitivity or inflammation markers to provide some context.
Thanks for the article and video! Having myself high levels Lp(a) I also researched it a lot trying to find an answer to why this high Lp(a) gene is still going around. It must have some kind of benefit and it does. So now I accept it as a blessing but knowing that I must keep my diet and lifestyle true to the ancestral living. I am on a LCHF diet, I exercise. My cholesterol has been up and down but no matter what my Lp(a) stays the same. Of course my doctor wanted me to take statins! No way! I went for a Calcium score test and everything looks good and I also tested for inflammation markers which also look good. But maybe I should test Lp-Pla2 as well? I also take fish oil. I’m thinking that this gene may have come from Northern ancestors who ate a lot of fish and did not have a lot of vitamin C? Maybe…Thanks again!
Hi! You’re welcome!
I know the feeling, and there does indeed appear to be some benefit (especially noted by having 0 Lp(a) doubling risk of cardiovascular mortality compared to the next quintile in one study…). My Lp(a) fluctuates by 40 nmol/L so far (although I intend to get more high frequency testing done) but yeah has stayed pretty much the same for me so far as well.
I do perhaps wonder if some of the risk associated with smaller forms of apo(a) (and thus increased levels) has to do with a different “carrying capacity” for oxPL, and thus higher susceptibility to being overwhelmed by oxidative stress – but that’s pure speculation on my part thus far.
It is interesting to note that Peter of Hyperlipid has a post up on the Bantu. They’re genetically related, but distinct, and one group is primarily vegetarian while the other is similar but consumes meat (fish). The vegetarian group has shorter apo(a) forms, and thus higher Lp(a) over all. Even when controlling for apo(a) forms, they still have higher Lp(a) – so he speculates they benefit from having more Lp(a) around, perhaps because of some facet of this dietary difference.
It’s interesting to think about at least.
As far as Lp-Pla2, I’m not sure of the usefulness of it yet. I got blood drawn just an hour or so ago and that was on the list, but honestly if I had to choose a Coronary Artery Calcium Score or Lp-pla2 I’d pick CAC every time. It’s an actual measure of the progression of the disease, while Lp-pla2 is a solitary marker in a complicated system, albeit one I’m interested in understanding better. That said it probably doesn’t hurt to check if you’re curious – just note that in the study referenced in the article the lowest tertile was <700 for Lp-pla2 so even if slightly elevated (e.g. 200s) it might not impact risk much.
So great to get some more insight on the role of Lp(a). I was diagnosed with FH when I was 23 based on high LDL, Lp(a) and ApoB (as well as the fact that my dad died of a heart attack at 56). At the time my Lp(a) was 484 mg/L putting me in the “very high risk” category. It was never checked again until last month (I’m now 33) and my level has drastically lowered to 191 mg/L. I’m not on a statin and the only difference is that I had started a LCHF the month prior to the blood test. When I was told about the high Lp(a), the doc said there was very little I could do to change it but I attributed the change to my diet. I was made to think that the high level was linked to my supposed genetic problem but realize this was not the case for me as my LDL has remained high but Lp(a) has dropped. Have you come across any links between Lp(a) and FH?
Hi Lisa –
Yes, it is typically the case that those with LDLR mutation based FH have higher Lp(a) levels than the general population, although whether that’s due to higher demand or lower clearance is unknown. Granted though, it could be both – genetically influenced to be a bit higher *and* influenced by diet/environment. Diet does appear to impact lp(a) levels, more specifically that higher carb, lower fat diets raise it, as does soy based protein over casein (milk) protein for example.
In some of the research I’ve read so far it states that probably about 30% of lp(a) levels are based on genetics.
So it could very well be that LCHF did lower your Lp(a) levels – similar (although not as drastic lowering) has been indicated to occur in experimental settings as well. I’ve never actually heard of Lp(a) lowering so quickly before, but it does seem like it is possible.
Thanks for that information. My two tests were 10 years apart so I guess other factors could be at play, but in terms of my diet, the only difference is that I’ve been eating low carb. My LDL and ApoB levels did not change though, and are both still considered high. I know low carb diets don’t really lower LDL (and can sometimes raise it), so is that the case for ApoB as well because they are linked? What are your thoughts on the importance of ApoB in all of this? I’m so happy that all of my lipid markers are the best they’ve ever been while being on this diet but also worried that LDL and ApoB are still high (though if I really do have FH I suppose ApoB will always be high?) .
Yes apoB and LDL-C are related. ApoB is measuring how many LDL particles there are, and LDL (or LDL-C) is measuring the “cargo” – how much cholesterol the particles are carrying as a whole. So, the two are linked, to a point.
There’s some evidence (such as from Virta Health) that LCHF can sometimes bring down ApoB/LDL-P but that’s normally in people who have high apoB due to inflammation. If yours is from FH I would doubt that it would go down. Although, I’m not expert in that regard.
As mentioned in this list (#1) the risk for those with FH doesn’t even seem to be related to LDL level anyway. The differentiating factor for those who had an event, and those who didn’t was actually level of insulin resistance. LDL level was about the same between the two groups. So perhaps that’s something you could look into – which is something I consider to likely be true for the general population anyway. Signs of inflammation and insulin resistance seem to be better predictive markers than LDL even in the general population (e.g. HDL levels, triglyceride levels, fasting insulin) from what I’ve seen so far.
Thank you Siobhan for your enlightening info on Lp(a). Mine is 265 nmol/L (high risk), and I have been trying to research ways to reduce my CAD risk for the last 2 years. I went vegan for 4 months; lipids and particles went up! Eventually had a carotid ultrasound showing moderate risk in left carotid and clear on right side. Also convinced a second cardiologist to order a coronary artery calcium scan, and it was 92 – high end of minimal risk range. I have seen 3 physicians trying to better understand Lp(a) and its particular risk to me. They all recommended statins because as one said, “Lp(a) doubles the risk.”. Thanks to people like you, Dave, Ivor Cummins and Dr. Jeffry Gerber, I have decided to not let one marker rule my health. My Lp-PLA is good along with ApoB, hs-CRP, Trigs and ratios. I am also very fit following a regular exercise/weight training program. I have been on LCHF for about 6 weeks now and feel this is the way to go. I plan to have another calcium score in 3 years and let the lipids be unless something warrants other testing. Thanks again. Good luck with your Lp=PLA test!
You’re welcome, and thanks on the well wishes! Just waiting for the results to come in now 🙂
Great to hear (from what I can tell) you had a CIMT and CAC done before going low carb (or at least close to when you started), that would be (and is) my plan as well to get one, then get follow-ups down the road. CIMT you could get even sooner (I believe Dave does every 6 months, and I intend to do the same) as well. Glad to hear that everything else is looking good, and I hope your follow up goes well! Glad to hear you have found something that you think will work for you 🙂
http://www.ravnskov.nu/2015/12/30/cholesterol-was-healthy-in-the-end/
This is a great read
Dr Matthias Rath has shown in numerous animal studies that LP(a) is the bodies defense when ascorbic acid (AC) gets too low. AC builds collagen and is a major builder of the ground substance in the walls of arterial walls. When AC is low, the liver produces a very sticky lipoprotein to plug the holes in the eroding blood vessels. When AC is restored to proper amounts, the body stops production of LP(a).
Dr. Raths work is an important piece of the LPa puzzle…some links for further study..
https://www.youtube.com/watch?v=VERKQsI2Kzg
http://www.drrathresearch.org/attachments/education/Cholesterol-Is-Not-the-Major-Cause-of-Heart-Disease.pdf
I think vitamin C deficiency is something that could cause higher Lp(a), but I definitely don’t think it’s the only cause. I think it’s likely that vitamin C deficiency can cause damage to the arteries, which would lead Lp(a) to go up to address that. It has roles in repair, after all.
But, as stated here it is used in repair of numerous tissues, and various different things can lead to raising or lowering (environmental, diet, etc) – if you get a cut it is used to heal that wound as well, if you have a hemorrhagic stroke it helps to clot, etc. It also has uses in cleaning up oxidized phospholipid and discarding them.
The vitamin C thing I think is one function of a very useful particle. Likely anything that leads to damage of the arteries, or an increase in oxidative damage, will lead to raised Lp(a).
Hello Siobhan,
I just watched your video and it gave me perhaps a glimmer of hope.
I have SUPER high Lp(a) It’s always been sky high ever since beginning testing a few years ago. I take every supplement under the sun, do Pauling Protocol. I’m 56 weigh 116, exercise, don’t eat animal products.
I’ve managed to tame most markers except for Lp(a) and Beta Sitosterol from a couple years ago when they were mostly horrid.
Total Cholesterol: 171 mg/dL
Direct LDL c 97 mg/dL
HDL-C 77 mg/dL
Triglycerides: 41 mg/dL
LPa 131 mg/dL should be >50
Fibrinogen 395 mg/dL Should be >370
Apo B 88 mg/dL should be >80
CRP 0.6 mg/L
LpPLA2 125 nmol/min/mL
MPO 324 pmol/L
A1C 5.5
Beta-Sitosterol 234 Super High( don’t know the reference range)
other sterols are in OK zone
They recommend Ezetimibe, as it blocks the cholesterol from being absorbed. I read that it blocks NPC1L1, which is the same pathway Vitamin K is used to get absorbed. I take K2 to hopefully removed calcified plaque. Wondered if Bile supplement would help with sterol absorption, but read it possibly can cause cancer(!?) I have those earlobe creases, and when I had my first mammogram, there were micro-calcifications at age 40 which happens they say every 1 in 10 cases at that age. Will get Calcium scan to see how much damage has been done over the many years without even knowing about these markers. Thankfully my ultrasound of carotid/aorta was super clear. Have you heard of Lp(a) being influenced to Hyperabsorption of cholesterol?
Do you know if a HFLC diet would exacerbate the hyperabsorbtion of the good fats?
Interesting – the main Lp(a) SNPS rs3798220 and rs10455872 both homozygous = good. Apparently the heterozygous versions can contribute to aortic stenosis. Curious about the ‘good’ version of an Lp(a) SNP. Sounds like an oxymoron to me.
Sorry for the War and Peace version, but I am kind of freaking out about this.
Thank you.
Hi Val,
No worries about the long message, the more detail about the situation the better, actually 🙂
I’m not too sure about the phytosterol absorption question, unfortunately.
I haven’t heard of Lp(a) influencing cholesterol/phytosterol absorption at all, nor the other way around (hyperabsorption of sterols raising Lp(a)), I’m not sure why they’d be related, if they are, unless the absorption of phytosterol is causing some downstream effect.
It does look like your lp-pla2, CRP, HDL, and trigs, are all in ranges I’d want to have… do you know if either of your parents also have high Lp(a)? And, do you know what your fasting insulin is? This is another marker I personally like to keep an eye on.
I’d definitely want to know the result of the CAC as well, and just remember that if it is high the key at that point, according to Ivor Cummins someone who has spent a lot of time looking into it, is to make sure the increase remains <10% during follow up scans...
The "good" Lp(a) SNP essentially just means it's a variant that generally results in lower Lp(a). I don't really think it's an oxymoron, as Lp(a) does have its uses in the body, the question is if yours is being "used" for anything, and that's why it's high, or if it's genetic.
One of the relevant questions is, what does your diet look like? You said no animal products, so what's a typical day of eating for you? Diet can impact Lp(a) levels as shown by quite a few tests - have you switched to plant based recently, and if so do you have before/after Lp(a) readings?
Good Morning Siobhan,
Thank you for your reply. I’m not sure if my parents have high Lp(a), but my father had a 3x bypass a few years ago. I asked him and he said he has never been tested for Lp(a). Makes me wonder…..
I’ve been plant based for a few years, and have only started having Lp(a) tested in 2013 and it was high then and in every subsequent test with crazy fluctuations but always super high.Prior to 2013 no doctor tested me for it and I had never heard of Lp(a).
I’ve recently cut down on carbs, and junk foods, eat fruit, vegetables, some nuts. After reading a little about low carb, I have cut out bananas and other high carb foods, or just have a tiny tiny portion-literally a bite or 2.
My fasting glucose was 97 on this past test and 99 in 2016. My insulin resistance (HOMA-IR) was 2.4 midrange should be 3 is considered high) Insulin-3 and C-Peptide are in ‘optimal’ levels. Sheesh—every lab is different with all the stuff they test for.
The test does not include Oxidized Phospholipids, but I just read this morning that they are carried around on Lp(a) particles!! Can I ask you: if my inflammatory markers are *good*(as per my first posting) (ApoB is in the low side of midrange), can I still have loads of Oxidized phospholipids floating around because my Lp(a) is so high despite my low inflammation and low bad particle numbers?? This would contradict your speech in the video, right?
I read that statins can sometimes cause an increase in Lp(a) (10-50%!!!) I *wonder* (although it is most likely remote) if the Red Yeast Rice is messing around with my Lp(a) levels, but again it’s ALWAYS been super high.
Thanks
FWIW there is some evidence that a vegetarian diet can cause higher lp(a), although whether that’s due to the high carb content or something else. Because you started testing after you went plant based (from what I understand?) I imagine it’d be rather hard to tell if it’s contributing or not, unfortunately.
Yes, oxidized phospholipid are carried by lp(a) so that they can be broken down and safely disposed of. Also, just because you have high lp(a) doesn’t mean you have high oxPL.
But lp(a) could also be non-genetically high due to other reasons. There are other factors that can raise it, as I’ve seen in my own results. Possibly things like low L-carnitine, refined carbohydrates, soy, sugar, and statin usage. Possibly also ingestion of seed oils (corn, canola, etc)…
If you’re curious about the red yeast rice, just remove it for 2 weeks or so and get another test and see what happens. Also see if any of the above are in your diet and see if removing them helps.
Also you said there were crazy fluctuations – do you remember the context around each test? Were there any notable differences between diet, environment, etc, between when it went low vs high etc? This could also be used to help figure out what is influencing it if it isn’t genetic.
Thank you Siobhan for your reply–I am learning a lot from you. I am making some serious adjustments to what I eat as I do consume many of the things you mentioned. Also have been researching Ezetimibe alternatives for blocking cholesterol absorption, as my B-Sitosterol marker was very high. Am finding some really interesting things like certain strains of probiotics–main one seems to be L. Acidophilus 4356:(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249224/inhibit absorption). It’s sold in Canada in capsules but requires refrigeration, so unwise to buy in this hot weather! Found a few others L. Rhamnousus GG which I did find on Amazon-they just arrived today, don’t think they’re as effective as L. 4356 but will try anyway. Also found a multi-strain probiotic in Florida which contains a couple strains which might block absorption–they are sending today in a cold-pack box. Who needs to go clothes shopping when you can buy strains of Probiotics!?
Quercetin + Luteolin also might inhibit absorption but only for 120 minutes, plus it doesn’t state the dosage. (http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0097901)
Ezetimibe blocks expression of NPC1L1 but this also blocks absorption of Vitamin K(same absorption pathway) which isn’t good. I am trying to find out if they mean Vitamin K1 or K2. Don’t care about K1, but K2 has many many benefits. I have been taking L Reuteri 30242 as it stated that it could ‘lower chole(sterol) absorption by 45%.’ Didn’t work for me, didn’t target NPC1L1, maybe that’s why.
I always search for a nutraceutical substitute to a pharmaceutical, and currently the only ‘drug’ I take is a baby aspirin, but I found out that there is a heterozygous Lp(a)SNP that responds to aspirin for lowering Lp(a), but I don’t have that variant, but take aspirin anyway.
Since receiving such crappy results a couple of years ago, and not taking any supplements at all at that time, I am now taking a TON of supplements, and they worked beautifully by slashing all my bad markers down into the good zone, save for Lp(a) and sterol absorption.
I just fear that all those years and years and years of eating rather poorly has got to have deposited some plaque in my heart’s arteries. Well, know better, do better.
Siobhan—do you have a lab that you like? One that works with the patient, and where you don’t need to provide a doctor’s referral? One where you can choose off a ‘menu’ of what you would like to test for? And one who can send the results to you and not involve a doctor? I feel that doctors don’t know much about stuff like this, and don’t want to waste my time going to ‘discuss lab results’ every time with my Dr.
Thanks!
You may have a genetic predisposition of high LPA production, which isn’t a bad thing as it aids to heal wounds. But it can get stuck on the artieres as it tries to ehal small wounds on the aertery walls. However being vitamin C deficient can cause it to skyrocket too. Even if it is genetic, supplementing with vitamin C could help, but at very high doses (1500 or higher daily). Since LPA acts as a surrogate for vitamin C, that could help your gene to go “hey! I’ve got other ways to heal! I don’t need to keep sending out the paramedics!”
Also taking proline and lysine can help, as they attract the LPA but help your body heal. Same with vitamin C.
Oddly, there is some evidence that ironically as contradictory as it may sound, a ketogenic diet can actually lower LPA levels.
lpa
https://www.sciencedirect.com/science/article/pii/S0735109718348162
Matthias Rath
https://www.theguardian.com/world/2008/sep/12/matthiasrath.aids2
Thank you Mike for the links. I will inform my Dr. about the Lp(a) study.
Hi Siobhan, Thanks for the article on Lp (a) and it’s commonly reported risk for blood clot. I am a Registered Nutritional Therapist now using Spectracell lab’s Cardiometabolic Testing and my personal report showed an extremely high level 74.7 mg/dl (reference ranges are 6-29.9) in Aug 2018. HDL is on the high side with a score of 89 and LDL at high of 140. Listening to Dave speak on Mike Mutzel’s High Intensity Health Podcast had me rethink this whole ‘cholesterol’ picture. Being a healthy and active person (1 to 2 hrs of various exercise per day including HIIT, Kickboxing, and Weight Training), with a body fat averaging 17% with high muscle mass at 36% (for a 51 yr of woman) using the Bioelectrical impedance method, on a low carb diet with overnight fasting for 14 hr most days, I question the Lp (a) score to be indicative of a compensation pattern to my high CK levels (was 1037 U/L in May 2018 now brought down to 584 U/L in Oct 2018 once I took specific supplements to help with muscle tissue repair (CoQ10, Carnitine, Serine, Calcium/magnesium, D Ribose, Asparagine, Fish oil – otherwise known as a mitochondrial support stack). After being on this stack, I will retest my Lp (a) to see if it’s shifted. Comments?
You mention high levels of CK – are you talking about creatine kinase? Just by the little I know of it I’m not supremely surprised it’s high, considering it has to do with muscle damage/repair. If you’re doing HIIT several times a week, it’d make sense for there to be repair going on.
As for the rest – I’ll be curious to see what it does to lp(a). Carnitine in itself has been documented to lower lp(a), alone. I’m not sure about the rest, personally, as far as what sort of impact they’d have – especially as it’s a lot of different things combined.
As I walk my followers through the results of all my blood work, on the blog post I am working on, I plan to send them to your website to learn more about cholesterol and more specifically, Lean Mass Hyper-responders.
Glad we can be of help to you and your followers! 🙂
Is there a relationship between CAC and liproprotein a?…..I had a CAC of 10 as a 46 yr old…(The 10 was all in RCA)… I’m 48 now….Recent testing history seems to be favorable..I’ve NOT had a lipoprotein a test but DID have a LP-LPA2 Activity test….Recent tests:
July 2018 Echo which revealed normal LV size & function, LVEF 55-60%..Normal RV function and normal diastolic function….Trace mitral, tricuspid, and pulmonic regurgiation..
Sept blood work:
Total cholesterol – 108
Trigelcerides – 111
HDL – 33
LDL – 52
Apoloprotein B – 61
LP-PLA2 – 92 (Quest Diagnostics range for this test is 70-153 with optimal being < 123…
hs-CRP – 0.3
Hcy – 14 (slightly high but some outlets have this number as 15 or < as normal)
I think some, but I’ve also heard it is context specific (e.g. low HDL, etc).
The homocysteine I’ve heard from a few people who deal with it often is ideally under 10, I believe it also relates to folate level, so B12 and folate may be worth looking at.
The HDL seems a bit low, and trigs a little close to where I’d take a second look at it, but were you 12-14 hours fasted during the test? The results of those two can be off if fasting too long, or not long enough.
If they are accurate, I’d probably want to look further at things like diet, etc, if it were me, as low HDL and high trigs (although usually higher than that) do relate to heart disease risk in themselves.
I saw this article while back about homocysteine levels, the answering MD thought it is more significant if > 50.. https://www.health.harvard.edu/heart-health/should-i-worry-about-my-homocysteine-level
I actually might have fasted too long for last round of bloodwork, as it approached 16 hours…Didn’t intend for that to happen, but by time I left work, got home, went to lab, took longer than anticipated….My trigs are usually < 100, though they have been over 100 few times….Usually do bloodwork 2x a year for about 2 decades now….
Ah okay, long term trends can tell a lot, luckily. If upon a re-test (or your next bi-annual test) they’re back to normal I wouldn’t be surprised.
One more thing, is there any consensus about which lipoprotein test is best?
1. Standard Liproprotein (a) measurement
2. PL-PLA2 Mass Test
3. PL-PLA2 Activity test
Lipoprotein(a) and lp-pla2 are sometimes gotten together. Lipoprotein(a) test tells you how many lipoprotein(a) particles you have (if in nmol/L), lp-pla2 is a marker of oxidative damage of lipoproteins. There’s a study that mentions lp-pla2 activity modifies the risk of lipoprotein(a) levels.
[…] Blog post mentioned: The Big Deal about Lipoprotein(a) […]
I have been taking hi doses of vitamin C I’m still in the 600s of my LP(a).
Also been dealing with back pain that travels down my leg. MRI does not show that I should be in this mich pain. Wondering if there is any coralation with this disease.
Not over weight, exercise regularly, look picture perfect but insides a mess.
Help!
Thank you for the great info! https://www.lipoproteinafoundation.org/page/UnderstandLpa is sponsored by
1. Amgen and 2.Arrowhead Pharm “Amgen receives a worldwide, exclusive license to Arrowhead’s novel, RNAi ARC-LPA program. These RNAi molecules are designed to reduce elevated lipoprotein(a), which is a genetically validated, independent risk factor for atherosclerotic cardiovascular disease.” Amgen anlos has drug Repatha to lower Lp(a).
3.Ionis Pharmaceutical and it’s subsidiary 4.Akcea published in The Lancet of Clinical Results with Lp(a) lowering drug.
4. Sanofi and 5. Regeneron has a drug Alirocumab to lower Lp(a)
6. Kaneka Medical Products has procedure to lower Lp(a) = Apheresis
7. Denka Seiken developed measurement of Lp(a) for clinical applications
Statement from the site:
“The Lipoprotein(a) Foundation is a patient-founded, 501(c)3 non-profit organization dedicated to preventing cardiovascular events due to high Lipoprotein(a) by diagnosing the most prevalent genetic risk for cardiovascular disease; educating and empowering patients and saving lives. We are fortunate to have such loyal and compassionate companies supporting our organization, and we thank them on behalf of the 1 in 5 people globally who have been affected by high Lipoprotein(a).
We do our utmost to develop strategic partnerships with companies who share our mission and values – saving lives by increasing awareness, advocating for routine testing, and supporting research that will lead to a specific treatment for high Lipoprotein(a). We invite you to make a difference by supporting our strategic objectives throughout the year. Sponsorship is a tremendous gift and demonstration of your commitment to the Lp(a) Community. Please contact serevill@lipoproteinafoundation.org. Thank you.”
Step one find a Lab marker to show risk
Step one(a) develop chemical to target the marker
Step two use the media and medical journal to scare the population
Step three get FDA approval
Step four make billions
Step five repeat from step 1
Was it the same with statins?
I have been LCHF for about 9 months, and my HDL has improved a lot, as have my Triglycerides. What is getting worse is my LDL, which is 254 alone, and my ApoB, which has gotten worse. My ApoA-1, on the other hand, has gotten better. I am reading that the ApoB is more of an indicator of heart issues than LDL. Do you have any info on ApoB?
Hi – could you post the full set of results (e.g. HDL, triglycerides)? It is difficult to comment without those as context.
Regarding apoB being a better predictor than LDL, I have seen that occasionally as well, and wonder if it is because apoB would include not just LDL but also VLDL and IDL which are remnant lipoproteins.
Hi Siobhan, I have been low carb for 5 months and and have managed to lower my lp(a) from 52.3 my/dL in September of 2018 to 28.9 mg/dL in April of 2019. Total cholesterol went up 100+points , ldl went up 100+ points. Super interesting since lp(a) hangs out on ldl. Lots of other interesting things happening with my cholesterol but lp(a) has been my most concerning number. I started taking the supplement Bergamot in addition to Keto. I’m pretty happy since the general thought is This number is hard to move. I Would love your thoughts on this.
That’s certainly interesting, Leslie. On the prior results did you also get any inflammation markers tested, or other things like insulin or anything like that? I myself have found that my lipoprotein(a) can vary from a couple different factors. For example: 1) It goes up when I fast for multiple days, 2) It goes up when I get sick (e.g. with a cold etc), 3) It goes down when I eat beef compared to pork (mechanism currently unknown), 4) It goes down when I eat a very high calorie ketogenic diet
So, I think it could plausibly drop for a couple reasons. So, curious about the prior bloodwork here! For example the full lipid panel prior (LDL, TG, HDL, total) to compare to more recently. 🙂
Hi Siobhan,
A friend has high Lp(a)=72 mg/dl with SAD, and two repeat testings in another laboratory 964 mg/l (SAD) and 851 mg/l (after 3 months of LCHF 20-50 g net carbs/day).
He does not have any other measured risk markers and is 43 years young.
Fasting LDL, HDL, TG, particles are large, Lp-PLA2, hsCRP, glucose, insulin are around optimal, normal blood pressure, BMI 24, fat% 12, exercises regularly, sleeps enough and well, and meditates.
His mother got first angina symptoms around 40 with elevated blood pressure numbers but with normal cholesterol numbers (BG and Ins not measured) which prompted MD to suggest possible genetic risk factor.
23andme-FT-DNA gives in Promethease rs10455872(A;G) 1,51x increased Coronary Heart disease risk. He could have many other polygenic risk factors, and rare family mutation but did not agree with whole-genome sequencing.
Could you help, I have trouble finding articles where there would be only one risk factor like really high LPA and the lifetime risk of having CHD?
Could the NHANES data have this kind of profiles with outcome data or some other source?
Best regards,
Noora
Hi – I’m not sure if NHANES collected lp(a) data, but if so I’d definitely be interested in seeing it. Regarding high isolated lp(a) there are a couple studies comparing against other risk factors like HDL, and framingham risk (which you can calculate with our report tool) which shows if all else good, it seems risk for lp(a) is low – based off of what we know so far, but this is not a guarantee. I’m in a similar situation (elevated lp(a), likely due to genetic reasons) and as such I’ve decided to keep a close eye on things like CAC, insulin, lp-pla2, hs-CRP, and framingham risk score as well as overall metabolic health.
EDIT: Although, to note, I have found that my lp(a) can vary quite a bit depending on protein source (pork vs beef), high fat feeding, fasting, getting sick in general, etc.
Hi Siobhan,
I have been following your investigation into lp(a) for several months having an initially high level myself of 135nmol/l, and being able to bring it down to 90 on LCHF.
This week Ivor did an interview with Dr, Paul Mason (part 1) and although only the first couple of minutes is all the time they spent on lp(a), there was a surprising statement made by Dr Mason. That being that lp(a) only attaches to an LDL lipoprotein if that particle is oxidized. This is interesting and on the surface goes against what I have come to understand. If, as he claims, lp(a) is a surrogate for something else, and the presence of lp(a) is strongly genetically defined, then it is a surrogate for something else that is genetically defined?
I’d obviously love to have your thoughts on the matter.
I have reason to get an understanding of this: I’m 61, have been fit all my life. Never smoked
And I was diagnosed via angiogram with a 30% distal LAD obstruction 10 years ago. Went Vegan, and 6 months ago found I was worse. Now LCHF and hoping for the best
Best regards and thank you for your work in this field!!
Chad
–==== CholesterolCode.com/Report v0.9.3 ====–
…6 months on LCHF (20g to 120g carbs) ::: 12 hours water fasted…
Total Cholesterol: 138 mg/dL 3.57 mmol/L
LDL Cholesterol: 41 mg/dL 1.06 mmol/L
HDL Cholesterol: 88 mg/dL 2.28 mmol/L
Triglycerides: 31 mg/dL 0.35 mmol/L
–CHOLESTEROL REMNANTS–
Remnant Cholesterol: 9 mg/dL 0.23 mmol/L >>> Lowest Risk Quintile
Remnant Chol to HDL: 0.1 >>> Lowest Risk Quintile
Go to https://tinyurl.com/y84u92wm for more on Cholesterol Remnants
–ATHEROGENIC INDEX OF PLASMA (AIP)–
AIP: -0.814 >>> Lowest Risk Third
Go to https://tinyurl.com/ycccmmnx for more on Atherogenic Index of Plasma
–CONVENTIONAL MARKERS AND RATIOS–
Friedewald LDL-C: 44 | Iranian LDL-C: 14
Total/HDL Ratio: 1.57
TG/HDL Ratio in mg/dL: 0.35 | in mmol/L: 0.15
As far as I’ve read the supposition that apo(a) attaches to oxidized apoB is unlikely because there is not a significant amount of free (unbound) apo(a) in human plasma, which would have to be true for this to be the case. The best case I’ve seen made for where apo(a) attaches to apoB is either 1) within the liver cells or 2) in the extracellular space of the liver (not in plasma), although we don’t know which. This would mean apo(a) would have to be attaching to unoxidized, “fresh” apoB on the newly formed LDL particles from the liver. There’s a lot we don’t know about lp(a) (freely, and oft admitted in the research), but we have some evidence to take a guess. Best guess is lp(a) is formed in the liver, not in plasma.
This is repeated in a paper from 2017 reviewing what we do and don’t know.
I’m not sure Paul’s view on the genetic levels of lp(a), but I definitely do think there is a strong genetic component, after which lifestyle influences around that baseline. For example, Dave and I both eat pretty similarly (mostly meat, mostly beef) yet his lp(a) is 1-3 mmol/L, and mine is 90-130 mmol/L. One of my parents also has similar levels of lp(a) to me – likely lending to that theory, along with the research behind it.
I intend to do a general re-cap of my findings with lp(a) later this year, it’s difficult to sum up in one comment. 🙂
Good luck to you on your health journey! I have heard of a couple of anecdotes of people reversing or stabilizing calcification with LCHF/keto so hopefully you experience the same.
Thank you Siobhan,
I saw this, this morning.
https://speciality.medicaldialogues.in/lower-lipoproteina-reduces-cvd-risk-irrespective-of-levels-of-ldl-c-finds-study/
The summary is inadequate and flawed in units in at least one spot. Perhaps you can find the actual study. I can’t
Thanks! I’ll see if I can find the original
This may be of interest.
Thanks!
1. Is it accurate that LP(a) only needs tested once since its a genetic number?…..
2. Also, do LP-PLA2 measurements change frequently like standard cholesterol numbers can or do they not move as much?..Do people test LP-PLA 2 with the frequency of other lipid tests?
3. I had a cartroid ultrasound a few months ago, and while it was deemed normal I didn’t see any mention of IMT score or anything like that…The final report listed no numeric measurements, just this language (for both right & left sides)
“There is no significant
atherosclerotic plaque demonstrated in the visualized portions of the
left common or left internal carotid artery. The peak systolic and
end-diastolic velocities are within normal limits in all measured
locations. There is no sonographic evidence of hemodynamically
significant left internal carotid artery stenosis”.
1. In my own experience, no. I’ve been able to manipulate by lp(a) through a variety of means including water-only fasting and high calorie high fat feeding as well as some other ways and seen pretty significant changes. Anecdotally, I’ve also heard people have seen their levels go down upon going keto, perhaps related to its nature as an acute phase reaction (other inflammatory markers also tend to go down on keto according to virta study). I suspect some context is needed for the levels.
Additionally, there’s a study I came across which noted that serially increasing lp(a) offers itself as a potential warning that something is going on, and this increase was paired with increasing hs-CRP. E.g. checking both over time may be a way to keep an eye on things, and thus may have a benefit over just testing once. I personally prefer to continue testing and keep an eye on them, as a sort of additional “check engine” light.
2. Yes, they do seem to change. In my experience (as well as Dave’s) they seem to follow LDL-P levels to some extent, although I’ve never seen levels higher than ~350 in myself or other low carbers so far, and the “low risk” cutoff for the statement mentioned is 600. The only time I’ve heard of lp-pla of >400 was in someone who actually had cardiovascular disease. So again, context may be needed, but I still test it every time to keep an eye on it.
3. It was probably a carotid doppler, which visually checks for plaque. You’d need to specifically request a CIMT (carotid intima-media thickness) test, which also uses ultrasound but actually measures the thickness of the artery wall. Both are useful, but CIMT allows you some actual numbers for tracking purposes. With mine, I was able to go back and request the images from the carotid doppler be interpreted, as the same type of image is used for a CIMT. You may be able to do the same.
Unlike standard cholesterol measurements, LP-PLA2 seems to have many different reference ranges depending upon which lab you go to……Quest LP-PLA 2 activity test reference range for males is 70-153, and they list optimal as < 123…Female range is 50-133….
Have you ever heard of the Ion Mobility Fractionation tests?….I had that done recently….Some of those numbers LDL particle size and LDL phenotype came back ABNORMAL, yet the one number that WAS optimal was LDL-P…..
This one MD seems to stress importance of LDL-P
http://eatingacademy.com/cholesterol-2/the-straight-dope-on-cholesterol-part-vii
My liproprotein (a) test, done in May was 32 nmol/L
Hi – this is actually true for many markers, as “reference ranges” are actually usually based off the clientele from that particular lab, so the reference lab in one area may be different in another state from the same lab. I’ve seen this with triglycerides, and a few other markers as well. That’s why I try to reference studies on the marker, as well as try to understand the mechanism, and context of the marker as opposed to just the reference range.
Yes I’ve heard of that test – without seeing the actual full results it’s difficult to comment, though. Some doctors do press on the importance of LDL-P alone, but I have a very different view from others that there may be good and bad reasons for LDL-P to be high (same for LDL-C), in other words I like to interpret my own labs with that context in mind. I would want to view the rest of the results, if it were me, to see that context in full.
Hi Siobhan,
I wonder if you still see these comments. You mention lp pla2 of 350, 400, and 600 in these comments. What units are you using? My lp pla2 is 260 nmol/min/
Thank you,
Laura
I have very high lpa and also auto immune disease. I have hashimoto and was on gluten free diet for almost a year and High protein /low carb diet. I have never had high cholesterol or high triglycerides . My numbers have been good all my life. I have belly fat when not on low carb diet of course. I had no symptoms of any problems . Carotids had normal calcification for 67 year old . Had good physical in Jan and in Feb had sudden onset afib and STEMI . Had heart cath done and CABG X 4 . Lad was blocked but no symptoms at all. So doctor told me it was hereditary factor since I didn’t meet the criteria for heart disease. If I hadn’t decided to have a cardiac cath while I was in the hospital I wouldn’t have known I was a walking time bomb. I didn’t know about LPa except it was a hereditary factor for imflammation. I had been going to a homeopathic doctor for the hashimotos and had been on numerous supplements . So who knows it they helped or not. My LPa is like 70 I think very high but I feel fine but I felt fine before the OHS. I guess I will go back on the Low carb diet again since that seems to be the best thing for me to keep my weight down . They said diet really didn’t have anything to do with my heart STEMI.
Can anyone help me understand these results? After my annual wellness check, doctor mentioned statins. She ordered additional tests, at my insistence, and I’ll be finding a new PCP because her office sent these results electronically without comment. (File attached if easier to read). I’ve been keto for almost five months. Thank you!
Result Name Value
Apolipoprotein B 142 mg/dL
Apolipo B/A Ratio 0.9 ratio
Apolipoprotein A-1 158 mg/dL
LDL-P 2,459
Small LDL-P 631
Cholesterol Total 270 mg/dL
LDL-C 194 mg/dL
HDL-C 60 mg/dL
Triglycerides-NMR 81 mg/dL
HDL P Total 30.1 umol/L
LDL Size 21.3
LP-IR Score 37
Hi, for a quick rundown:
Apolipoprotein B is an identifying protein on lipoproteins like VLDL, chylomicrons, LDL, etc. Each lipoprotein has 1 apoB.
ApoA1 is found on HDL. The ratio between apoB/apoA1 has been proposed to work as a proxy for insulin sensitivity, but I personally like to look at the numbers in context and not at the ratio alone.
Small LDL from what I’ve seen so far is often around 30% or less of total LDL-P in metabolically healthy people, which yours is.
LDL-P is often LDL-C x10 +/- 15% in metabolically healthy people as well, from what I’ve seen, which you are pretty close to.
And I’ve also taken the liberty of running your lipid numbers through our report tool as well. • Coffee: • • Cholesterol Rx: false •
–===== CholesterolCode.com/Report v0.9.5.15 =====–
• Female •
• 14 on months on Keto (less than 20g carbs) •
•
Total Cholesterol: 270 mg/dL 6.98 mmol/L
LDL Cholesterol: 194 mg/dL 5.02mmol/L
HDL Cholesterol: 60 mg/dL 1.55mmol/L
TG Cholesterol: 81 mg/dL 0.91mmol/L
———RISK REPORT———
Atherogenic Index of Plasma: -0.231 mg/dL >>> Lowest Risk Third
—-> Go to https://tinyurl.com/ycccmmnx for more on AIP
Framingham Offspring: 0.7 Odds Ratio >>> Low Risk
—-> Go to https://tinyurl.com/y5fc5adl for more on this Framingham study
Jeppesen: >>> Lowest Risk Third
—-> Go to https://tinyurl.com/y63xp7lj for more on the Jeppesen study
———OUR COMMENTS———
**This does not constitute medical advice**
• Your triglycerides of 81 mg/dL are typically considered optimal.
• We would consider your HDL of 60 mg/dL as strong.
• We’d consider your LDL cholesterol as in range for what we’d call a “Standard Hyper-responder”. This is common for many going on a low carb diet. For more on hyper-responders, visit cholesterolcode.com/hyper-responder-faq. For a deeper explanation on our proposed mechanisms for this when powered by fat, see CholesterolCode.com/model.
I have a low Lipoprotein(a) -14, but high LP PLA2 Activity (148). I’m not seeing anything in this article about that. Are there any other articles you’ve written that would address this?
Hi – we don’t have any articles about this in particular (although perhaps we should!) but Dave and I have both noticed in our data that lp-pla2 tends to follow with LDL-C and LDL-P. I suspect this is partially because it’s a marker that is actually carried by the lipoproteins, so if you have higher LDL than the general population lp-pla2 may be “out of range” but still proportional to your LDL. Hopefully that makes sense!
What is your overall lipid profile, if I may ask? (E.g. HDL, TG, LDL)
Note, also, that in the graph used lp-pla2 of <600ish is "low risk" which you are far below. It may also help to get some further context via other inflammatory markers too though (such as hs-CRP) to double verify that.
I am very interested in the references you site but i can not find them listed in this blog or on the Cholesterolcode website. Where can i find them?
Hi – right below the video at the bottom of the post there’s a button that says “Sources”. If you click on that it will expand with the citations used. 🙂
Hi Siobhan and Dave,
Thanks so much for all that you do! I have been following you guys closely for about 6 months now, ever since I moved to a LCHF diet. I am somewhat unique in that I have RIDICULOUSLY high LP(a) of 564 currently. My dad is an Internist, and he referred me to a cardiologist. For awhile I was taking 20 mg Crestor and 10 mg Zetia, and the cardiologist recommended that I take repatha as well.
I am 42 years old. Here were my numbers in May 2019 while taking 20 mg Crestor and 10 mg Zetia. At the time, I was 6’4 and 240 pounds. No exercise, no coffee, and ate a crappy western diet:
May 2019
Cholesterol, Total 148
HDL Cholesterol 43
Triglyerides 129
LDL- Cholesterol 82
OxLDL 34
LDL Particle # 851
LDL- Small 164
LDL Medium 177
LDL Pattern B
Apolipoprotein B 85
Lipoportein(a) 600
HS CRP 0.7
LP PLA2 Activity 139
Hemoglobin A1C 6.0
Insulin Intact 17
C-peptide 2.93
In June 2019, I learned about LCHF and decided to get serious about diet and even get off the medication. I lost 45 pounds. So in Nov 2019 (current weight of 195 pounds, still no exercise and no coffee), here were my numbers without the influence of medications (which I had stopped taking about 3 months prior):
Nov 2019
Cholesterol, Total 263
HDL Cholesterol 37
Triglyerides 86
LDL- Cholesterol 206
OxLDL 72
LDL Particle # 1,866
LDL- Small 439
LDL Medium 492
LDL Pattern B
Apolipoprotein B 157
Lipoportein(a) 564
HS CRP 0.7
LP PLA2 Activity 199
Hemoglobin A1C 5.6
Insulin Intact <3
C-peptide 1.17
Just curious if you guys have any comments or thoughts? I was hoping LCHF would increase my HDL, but I have historically hovered in the 30's. My Dad (Internist MD) was excited about my recent A1C and insulin numbers, but nervous with my LDL numbers (in particular small LDL which appear to be high for a LCHF diet?). And of course he is very concerned with the high LP(a) numbers. He thinks I should at least consider taking a small dosage of statins to bring the LDL down.
FYI- My CAC score in August of 2019 was 27.6.
Thank you in advance for any thoughts or comments!
Dave
Hi – one note on the HDL is I’ve been in the same boat. Prior to keto, my HDL was around 33, and I’ve been keto for 3 years – over which it has slowly risen to 50s-60s. So, in my experience it seems it can sometimes be a time thing, assuming everything else is indicating resolution of metabolic syndrome (e.g. low inflammatory context, trigs low, insulin normal, etc). This is going off of what I’ve seen in myself and some others. So, perhaps it’s similar for you – I don’t know of any way to tell other than just to see if it does come up over time, although it’s of course up to you on what you decide to do on that front.
Regarding the other markers, it’s pretty much what I would expect. Dave has shown that oxLDL can follow LDL under the influence of metabolism. We’ve also seen that in metabolically healthy people, small LDL can likewise follow with LDL-P – and (again in metabolically healthy individuals), tends to be <30% of total LDL-P (which yours is).
As for the lipoprotein(a), I can really say whether it is or isn't of concern. I also have high lipoprotein(a) (90-140 nmol/L depending on what I'm doing), and ultimately what I decided to do was read through the research and decide on what I was comfortable with longterm, same for higher LDL.
You may find that the cholesterolcode facebook group may be of use – there are some others with high lp(a) who may be able to offer their own opinion and further research than what is covered in this post. They also provide studies/discussion on LDL as well, which may be of use. 🙂
Very interesting and insightful article. I am on a journey with trying to figure my high LPa out. It was around 373 nmols and went up to low 500’s after taking crestor/statins for 3 months. So now I am on repatha. I had 6 heart stents put in last year with a ct calcium score of 490. The interesting thing is I have an older sister. She is overweight and never exercised. Her LPa was 100 points higher then mine. She has no issues. I have been an avid exercise person. Low fat eater but high carbs. I know the high LPa cannot be the main reason for my issues otherwise my sister would have issues too. My next step is to try keto and stop repatha as I think repatha is not agreeing with me. So hearing your talk and reading the article gave me some new thoughts about LPa. Thank you.
Glad the article/video was of interest – although I’m not a doctor, and thus can’t give medical advice, if I were thinking of adopting a new diet (as I did 4 years ago with a ketogenic diet) one thing I’d wish I’d done was get some baseline bloodwork to get a look at the big picture so I have something I can compare to later. I also know some people, if their primary concern is cardiovascular disease, who get additional baseline testing like a CIMT, CAC, carotid doppler, etc. If it’s something you wanted to do we have a list of our favorite blood tests here. I wish you the best of luck on your health journey, regardless!
Hello, I have read this article and watched your video. Thank you for this great information that I only half understand! 🙂 In November 2019, I was tested for Lp(a) and my number is 154.2. Supposedly the number should be <75. So I’ve been trying to lower my cholesterol (304) and my LDL (238) by decreasing fats and oils, taking high doses of Vitamin C, taking Niacin, Proline, Lysine and trying to prevent a stroke by taking Nattokinase. However, your research seems to cause me to wonder if all of this is necessary. I’m 56 years old, a female. My parents are both living at the ripe old age of 86. My mom takes no medications. My dad has been on statins for 40 years. No hx of heart attacks or strokes in either parent. My cholesterol has ranged, over the years between 189 and now 304 (the highest). Does menopause ever cause cholesterol to rise? More information: My hsCRP is 0.78. My LDL-P is 2274. My small LDL-P is 883 (high). My HDL size 8.2 (low). My LP-IR score 37 (normal). Do you recommend that I get tested for Lp-PLA2? I’m so utterly confused. Any information you can give me is much appreciated! Thank you in advance. Also just sent you a friend request on Facebook.
Hi – you are welcome! Unfortunately, I can’t say whether or not lowering lipoprotein(a) in an overall healthy context is necessary for a couple reasons. 1) I’m not a doctor and thus can’t give medical advice and 2) I genuinely don’t know. I’ve not seen a study comparing two cohorts of truly healthy people (e.g. non-hyperinsulinemic, no metabolic syndrome, low inflammatory markers) one with high lp(a) and one with low lp(a) and comparing their outcomes (CVD, all-cause mortality, stroke, etc) so I honestly don’t know if it increases risk in that context or not. I’ve seen plenty of discussion and debate over this topic, for sure.
I also have high lipoprotein(a) (around 115 nmol/L or so, depending on what I’m doing), and generally appear to be overall healthy – but I still live in that state of cautious optimism tinted by genuine uncertainty.
What I decided for myself, to make me comfortable, was keep a very, very close eye on things (inflammation markers, insulin, overall metabolic health and cardiovascular disease markers – CIMT [measures thickness of the arteries in the neck], carotid doppler (checks blood flow in the same arteries as well as visually checking for plaque), CAC (baseline, since I’m young, checks for calcium deposition in the arteries), etc. That way I can spot anything worrying early.
But others with high lp(a) do what you were doing – trying to lower it for their own peace of mind.
I think both approaches are valid – same for people who take similar approaches for high LDL (seeking to keep a close eye on things, vs seeking to lower it).
Ultimately we all have to read through the available research, discuss with our doctors/healthcare team, and then decide what would make us most comfortable in the long and short term with the understanding that we can always change our mind from further information that comes in later.
As for lp-pla2 – I do keep an eye on it, for myself. We have noticed it can be influenced by metabolic changes though, specifically regarding anything that can influence LDL-P levels. So, let’s say I do hypercaloric high fat feeding – this drives my LDL-C and LDL-P down and lp-pla2 will follow proportionally. Likewise if I extended fast (which I’m actually doing now) this will drive LDL-C and LDL-P up and lp-pla2 will also go up proportionally. So I try to take context into consideration with its level as well. In people who are metabolically unhealthy I have seen lp-pla2 be disproportionately high though, hence why I continue to keep an eye on it.
I’ve also started adding in GlycA as well, which is a systemic inflammation marker. It’s less overly sensitive than hs-CRP (e.g. exercise or even slight colds can spike CRP; I don’t consider this a bad thing, just worth noting) and seems not to be influenced by general energy status as much as lp-pla2 (e.g. in experiments dave has done there were no big swings from hypocaloric or hypercaloric diets). I get all of them, but I’ve been liking glycA so far as an add-on. Just thought you’d find that interesting! Definitely not meant as medical advice. 🙂
So, what I do for myself (which is not necessarily the “best” or “optimal” thing to do, just what I find comforting based off of the research I’ve read paired with my prior family history of CVD) is keep an eye on the big picture from multiple angles over the long term. But, like I said, if someone decided to seek to lower lp(a) because that would help them be more comfortable I think that’s valid too.
I hope that helps give you a bit more to think about/discuss with your healthcare team. I don’t feel there’s any “perfect” answer at the moment, so I can only supply information for you to consider – the rest is up for you to decide.
P.S. I accepted your friend request!
Hey Siobhan (love your name, by the way), thanks for responding and the great info! Much appreciated. I just printed out the slides from Dave’s “Diving Deep into Cholesterol” talk and watched it for the second time. Such great info. I love this website!! Feel like I’ve hit a gold mine. I donated and will again in the future. So, I have been taking 400 FU’s of Nattokinase on a daily basis for probably close to 3 years now. I started taking it prior to even knowing that I had high Lipoprotein(a). I kind of think of it as my blood thinner instead of taking a baby aspirin. Have you, personally, any thoughts on it? There is at least one article out there saying that it is a promising treatment for CVD’s. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043915/ I recently did some modified fasting–1 to 2 very low carb/calories meals per day 5 days prior to blood work and my total cholesterol, LDL, Lipoprotein(a) and triglycerides went up and my HDL went down–nothing too drastic, but is that normal? Did I skew my bloodwork with this approach? Also, what would be a bad reason to just go completely vegan and cut out oils–except for nuts, seeds, nut milks and fresh avocados? Seems like there is so much literature out there supporting reversal of heart disease by going this route. As always, thanks in advance for your perspective. Oh, shoot, one more question…I have always had low hsCRP numbers indicating low systemic inflammation. Wouldn’t this also indicate that I have low vascular inflammation and that everything is good? I don’t have metabolic syndrome or insulin issues either.
Hi Renee, thanks for the compliment and thanks for donating! I haven’t really looked into nattokinase, honestly. I tend to focus on the function of lipoprotein(a), and overall metabolic context, so it’s not a focus of mine, personally. Regarding your fasting results, although I’m not a doctor and can’t give medical advice, it is what I would expect from what you described. This would follow the inversion pattern, explained by the lipid energy model – which in my own fasting experiments lipoprotein(a) also follows. Dave has shown this also happens – to a lesser extent – with lower calorie compared to baseline as opposed to full on fasting.
So, yes, if I did something similar I’d suspect it would skew my results in exactly the way you described. This is why before any bloodwork I try to eat normally (e.g. baseline/maintenance calories, and food that’s typical for me) for the 5 days leading into the test as LDL-C and LDL-P have a 3 day window and 5 day window respectively wherein diet changes during those periods can influence the results.
As for the question about veganism, I can’t say whether you should or shouldn’t change your diet or follow a specific diet, etc – again I’m not a doctor. Likely if I wanted to change my diet in some way to decide if it was right for me I’d get baseline bloodwork after following my normal diet for at least 5 days (described above) 12-14 hours water-only fasted to get a snapshot of my current state. Then I’d switch to whatever diet I was considering, and after some time (at least a month, perhaps as many as four depending on what I was looking for) and evaluate from there along with how I feel, etc, and do occasional check-ins after that. That way I could see how I personally responded to the diet, and if it was helping me reach my health goals.
I do know that it’s recommended to supplement with certain vitamins etc if going vegan longterm, of course, but it’s worth mentioning anyway – you’d likely need to check in with your doctor to see which are recommended, etc. One person you might want to check out is Carrie Diulus (@cadiulus on twitter), who’s been vegan keto for quite some time. She’d likely be a good resource, if that’s a route you wanted to consider, as well as the Vegan Keto Made Simple facebook group.
Regarding CRP, it is highly sensitive – even exercise can spike it from what we’ve seen. But with any marker I like to take a look at the full context, not just that one marker in isolation. So, also looking at insulin, other oxidative markers like GlycA, HDL and triglycerides, etc. This helps to get a look at the bigger picture – but CRP is one thing I definitely do pay attention to, and consider part of the whole I take into account when looking at my own bloodwork results.
Something I also see many people doing (although this isn’t advice of course), if heart disease is a concern, is getting physical measures like CIMT (carotid intima media thickness via ultrasound), carotid doppler (measuring blood flow and visually checking for plaque via ultrasound), CAC (checking for calcium in the arteries), etc to get baselines and check-ins after any changes. This is also something I’ve done for myself and check back in on occasionally (depending on which measure it is – some are less frequently done like CAC).
Hopefully that helps, and good luck with your experimentation if you decide to move forward with it. 🙂
Sorry, I also meant to add that my HDL is 51 and my Triglycerides are 73. Both good. (this goes with comment below). Thanks.
Siobhan would it be correct to assume that anyone with atherosclerosis ( total blockage in one artery on which was performed a catheterized angioplasty and 2 stents in a further artery, would have high Lp (a).
Thank you.
Hi, I’m not a doctor nor an expert, but I don’t think I’ve seen a study showing this – even those with a low genetic baseline can get heart disease. However, I have seen a study or two showing increases of lp(a) in the years prior compared to their normal baseline and in particular this increase associating with CRP (inflammatory marker) – which may be a sign that lipoprotein(a) serially increasing in that study may have been relating to increasing need for inflammation and poor overall health. Hope that makes sense!
Hi Siobhan, did you take CaC or CIMT test? Having high lp(a) myself, would like to know the results you got?
Yes, I’ve gotten both. Baseline CAC was 0 (nothing particularly interesting for my age), both CIMTs I’ve gotten have been in the normal range for my age with no visual plaque.
Would that mean having a high lp(a) with other markers on point ( including LP PLA2 ) is ok? My triglycerides are 50 and hdl is 58, LDL is 120.HbA1c is 5. Plan on getting a CaC myself.
I can’t say whether it’s concern or not, given I’m not a doctor and can’t give medical advice. I did do a presentation on lp(a) recently, where I discuss the possibility in more depth, but I think for the time being everyone has to investigate this question for themselves (preferably with the help of their healthcare team) and decide for themselves what they’re comfortable with until we get more information on high lp(a) in healthy people over the longterm.
Hello,
I just got a test back. I am way out of range on one thing, I thought I best ask.
Opinions, please, on the below results.
Total Cholesterol 15.83 mmol/L (Range: 0 – 5)
LDL Cholesterol 13.9 mmol/L (Range: < 3)
Non HDL Cholesterol 14.56 mmol/L (Range: < 4)
HDL Cholesterol 1.27 mmol/L (Range: > 1.1)
Total Cholesterol : HDL 12.46 ratio (Range: < 4)
Triglycerides 1.45 mmol/L (Range: < 1.7)
Apolipoprotein A1 1.35 g/L (Range: 1.08 – 2.25)
Apolipoprotein B 3.78 g/L (Range: 0.6 – 1.17)
Lp PLA2 1727.9 U/L ^6 (Range: 0 – 560)
<560 Low Risk
560-619 Intermediate Risk
620-634 Borderline risk
>635 High Risk
ApoB : ApoA ratio 2.8 Ratio (Range: < 1)
CRP HS 0.44 mg/L (Range: < 5)
Background:
Carnivore 10 months. Fasted ~14 hours. No coffee. Lean < 10% Body Fat.
Warmly
John
Hi John, thanks for commenting. Because I’m not a doctor, I can’t give any medical advice, but I can offer my thoughts if I feel they may be of interest.
There are a couple things that stand out, name the higher than expected triglycerides, and the lp-pla2.
Typically if higher than expected triglycerides is paired with normal/expected level of HDL it usually indicates something has confounded the test. You mention being fasted for 14 hours – was this water only fasting? You say no coffee (in general, or just during the fasting period) but what about tea, or caffeine generally?
If you were water-only fasting, if it were me I’d want to investigate this more. For example, could you describe what a normal day of eating typically looks like for you (or what it looked like in the week leading into the blood test)? Any liquid fats consumed, particularly in the days prior?
As for the lp-pla2, Dave and I have noticed that lp-pla2 activity (measured in nmol/min/L) generally follows with LDL-P levels – sometimes to the point of being a bit out of range. But because I’m unfamiliar with the measurement yours is in (U/L ^ 6) it’s tough to say if Lp-pla2 levels in general generally tracks with Lp-pla2 activity levels we would expect to see given the context.
It may help to reach out to the CholesterolCode facebook group and see if anyone else has gotten the Lp-pla2 test and what result they had, for comparison.
If I were concerned regarding a similar situation, I’d likely want to follow-up with additional testing to verify the context and get a look at the bigger picture, as well.
Really good article. Same situation here with high Lp(a) around 70 mg/dl. I just found an article from Nov 2020, where your findings Siobhan get validated. A reduction of 30/40mg/dl with a LCHF diet. Hope it helps.
https://nutrition.bmj.com/content/early/2020/11/19/bmjnph-2020-000189
Thanks for the linkage! Although I’m not a doctor, based off of what I’ve read/seen so far, I would suspect what impact a ketogenic diet would have would likely depend on the context of the person in question.
I have heard quite a few times from people that their Lp(a) has come down on a ketogenic diet – usually from people who were having health issues prior. This would make sense if an inflammatory context was elevating lp(a) above their normal baseline.
However, with myself as an example, my lipoprotein(a) is still above range pretty significantly, but I suspect this is due to a genetic baseline (I’ve had both parents tested to confirm one or both had similar levels. One did) – something I’ve seen in others as well even if all other markers look excellent. The split of those with high lp(a) on a ketogenic diet seem fairly random and scattered – I’d suspect this is likely largely influenced by the genetic component at play.
I discuss much of this in my presentation on the topic from Low Carb Houston, as well.
Siobhan,
Thank you so doing all this fabulous work on lp(a)! I am finding it crazy difficult to find a doctor who is educated on this and will consider anything other than statins… am very frustrated.
So… my Mom was on apheresis here in Germany for 8 years. Triple bypass, PAD and many other issues…decades of smoking probably didn’t help.
About 10 years ago, my own lp(a) was at 30mg/dl – I recently checked again at 53 years of age and found it to be at 52 mg/dl. After some worrying (which I am VERY good at) and some online research, I suspected estrogen was the culprit – so I ended up experimenting with transdermal (maybe oral would have been better…) HRT and a few supplements (light version of Pauling + l-carnitine + gingko). After 3 months I have achieved NO beneficial impact on lp(a)… in fact, it went up to 63 mg. Bummer!
A few other random numbers: LDL: 158, HDL: 78, Trigs: 75, CRP: 0.6, Glucose: 68. I am 5’9″ tall and weigh 134 lbs.
Re: tests: Am wondering whether you would recommend additional tests (lp-pla2 activity?) Also trying to understand this whole particle size thing… How do I even ask for LDL / lp(a) particle size? (Do I tell them they need to measure in nmol instead of mg?) Let alone lp(a) “tail” size, or oxidative stress?
Re: diet: I eat mostly paleo (+dairy), but not super strict. I followed your diet experiments with great interest – looks like both the short-term increased fat and carb intake made LDL and lp(a) drop. But what does this mean for a lipid healthy long-term diet?
Any thoughts on paleo? Oral estrogen? Supplements?
THANK YOU,
Sabine
Hi Sabine,
Thanks for commenting. Though I’m not a doctor and can’t give medical advice, I can offer my thought where they may be of interest. For example, you may be interested in the presentation I did regarding lipoprotein(a), as it has some updated information compared to this post.
Out of curiosity between when you last tested and the more recent tests do you happen to know if your LDL-C also went up alongside lp(a)? Or any other markers to lend context? As mentioned in the presentation I’ve noticed that my lipoprotein(a) tends to follow my LDL-C in certain situations – typically when LDL-C seems to be influenced by metabolic factors (e.g. diet, fasting, etc). So if I were in a similar situation I’d likely want to check against that, as well as other markers so I could work with my healthcare team and determine the context.
As for which tests, we have a list of our favorites here. Whenever trying to determine larger context of something, the tests listed there are usually what I personally choose to get. Along with GlycA, which I’ve been more interested in lately.
To get particle count, typically you can ask for an NMR Lipoprofile, but the specific name may depend on the lab you’re getting tested through.
I’m not sure about ways to lower through e.g. pharmacology. I’m not super familiar with the research on that end, and more importantly I’m not a doctor so am not really comfortable speculating. But, perhaps Sam Tsimikas (who is a lipoprotein(a) researcher) may be able to point you towards some general resources that may be of interest. Or you could ask in the Cholesterol Code facebook group and see if other people there have been in a similar situation and can share what resources they used so you could discuss potential options with your doctor and go from there.
Hi Siobhan,
I had thought that LP(a) was a number that was pretty much set in people when they were young and changed very little in adulthood…..I had my LP(a) measured in 2019, it was 32 /nmol (the reference range for optimal at my lab was < 75 nmol)….Couple weeks ago with some other bloodwork the LP(a) was done again…This time it was 39 nmol….So while 7 pts might not seem like a lot, that is still 20% higher…..
Does LP(a) tend to remain constant or are 15-25% changes with subsequent more common?
Hi Rick,
I’m not a doctor and can’t give medical advice, as I’m not a doctor, so I can only share my thoughts in case they may be of interest.
You may want to watch my presentation from Low Carb Houston on Lipoprotein(a) as it may be of interest.
In myself, I have noticed around 10 nmol/L variation even keeping diet the same which I would consider “expected fluctuation” of the marker in myself. In Dave, whose lipoprotein(a) is much lower (around 3 nmol/L or so if I recall) I’ve only really seen around a 1 nmol/L fluctuation in his case, so the level of expected variation may depend on the baseline level you’re starting from (small absolute fluctuations in lower baseline levels).
I’ve also noticed fluctuations that appear to be metabolism induced, such as during fasting or hypercaloric ketogenic experiments such as this one, suggesting that diet may also influence around the baseline even in less extreme cases (presumably with correspondingly less extreme differences as a result).
And, of course, Lipoprotein(a) has also been noted as an acute phase reactant aka can significantly increase as a result of inflammatory signaling. (metabolism and inflammation related influences are both discussed in the presentation linked above).
So, when looking at my own results I typically look at a couple things –
1) Is it an amount I would expect for normal fluctuation based on my testing over time?
2) If not, did I change anything between the tests diet wise? E.g. eating more or less than normal, change in fasting time before blood draw (e.g. non-fasted, vs 12-14 hours water-only, vs fasting 18 hours plus/24+/multiday), change in diet composition, etc
3) Did I get context markers that may provide more information regarding the change (like inflammatory markers)
4) Is it a one-off (increased then decreased or stayed the same on a subsequent test) or is it a trend (continuous increase over more than two tests), etc
I find that these help me establish context for the three “influences” I’m generally aware of for lp(a) (genetic baseline including expected fluctuation, metabolism and diet changes, inflammatory signaling). It’s difficult to say in your case from two tests with a longer time between them as various things could change over that time that may influence the results, but further tests over time and additional context may help provide some additional information that may help clarify.
Thank you so much for this research. I’m a seemingly fit and healthy mid-30’s male and found I have lp(a) levels around 250 nmol/L. Heart disease at early age runs in the family too. Glad to happen upon you in an older podcast.
Hi Wes, I’m glad to hear the post was of interest to you. You may also be interested in my presentation on lipoprotein(a) from Low Carb Houston, as well, as it has some updates that aren’t in this post.
Siobhan Huggins, I am a 30 year old and found out I had raised lp(a) age 25 years old. I had a CAC done then and it was zero. At the time I had digestive issues, a had been carrying parasites but also a virus that had caused me inflammation from what I was told and at the time my lp-pla2 was just slightly elevated above the recommended levels.
I booked in this year for the tests to be re-done but the timing fell 9 weeks after having covid. My lp(a) had dropped but is still high using the guidelines and also my lp-pla2 was still slightly elevated. I had another CAC scan which again came back as zero and I was told that I should get re-tested again 6 months after covid as the virus will have increased inflammation. It also caused my ferritin to elevate which is an inflammatory marke and has been seen in studies to elevate with lp-pla2 in people who have or have had covid so I wonder if this was my cause for the recent results being high.
Thoughts Siobhan.
Hey Siobhan. I’m a white male that just turned 39, and ultra-health conscious. I found out two years ago I had an LP(a) level of 138 nmol/L. After mega dosing Pauling Protocol (Vit-C, Lysine, Proline) for like six months my LP(a) only reduced to 137 nmol/L. I really liked your article here, as most information is all doom and gloom about this subject. I was wondering if you ever got the CAC or CIMT? I saw like 4 years ago you were talking about getting them done. The other thing I was wondering is, what do you think the best approach to this problem is? I see your views on perhaps lowering LP(a) might not be the angle we should take. But what is? Should we try to some kind of supplement that involves blood clotting, as LP(a) has been known to wreak havoc. Should we just focus on reducing ox-ldl, or ramp up on endothelial health? Because it feels like I’m just sitting back waiting for the inevitable heart attack. It’s been a few years since your article. Is there anything new you’ve learned?
I have a genetic predisposition to producing more LPA than most. I’ve heard that it could be a surrogate for vitamin C, as it aids in healing wounds. Everything else on my blood test results looks pretty good, but my doctor immediately ordered a statin, which upon research, I became furious over. Statins can RAISE LPA!!! In the event that LPA could be a surrogate for vitamin C, I’ve decided to use high vitamin C intake instead of taking something that could lead me into depression and anxiety (I had the misfortune of being put on red rice yeast several years and and suffered sore muscles, joints, anxiety, depression, anger, and sleep difficulties at 120 mg a day).
I can only presume she ordered it because lowering LDL cholesterol would help cut risk, but if my triglycerides, LDL and HDL is fine, then what the f***? My doctor said that I am nearing the risk of heart attack of stroke with my levels being so high, but now I’m taking vitamin C (starting with 500 to 1000 mg in tablet form, plus some orange juice 2 to 3 times a day, which being 60 mg per bottle would top it at 1180. I have a blood test in 6 weeks. I might increase my dose after 2 to 3 weeks.
Also, lysine and proline can help as they tell the LPA to bind to them instead, while they help to heal wounds in the arteries that the LPA is sticking to in order to heal the body. It’s there for a reason! It was described to her as “deformed” (and thus inherently BAD) thing to have in the body, but the deformity could have benefits, as if it’s more sticky or shaped with an extra hook on the end, it could be more effective at healing damaged tissue that those with “normal” LPA particles.
A member of my family is on statins and she told me that it helped lower her LPA (has the same genetic APOB is i do), and that eating a medetrainian diet made hers fluctuate (but without vitamin C supplements it can be hard to get enough vitamin C I’ve learned! The body doesn’t store it!) Maybe she wasn’t getting enough vitamin C? So it could be statins work for her, but with my symptoms on the RRY, I’m very skeptical of doing ANY kind of statin (or an other pharmaceutical drug that blocks my body’s ability to do something when natural, less “invasive” methods could be an option.
I recently went on for my blood test and while everything looks great (triglycerides, LDL and HDL) my LPA was nearly 3 times what it “should be” (in ‘healthy’ people). I found that I have a hereditary condition which makes my body produce more LP(A). Naturally my doctor ordered a statin for it, as she said I was at “high risk” for heart attack or stroke, but I’m also taking vitamin C to heal any wounds in my arteries in the event there is some kind of risk there.
I’ve heard that a carnivore diet can lower LP(A), but when I was on a more carnivore diet I didn’t feel well. I’ve added a LOT more vegetables and plant fats (coconut, high oleic oils, olive oil, seeds, nuts, etc) to my diet and I feel SO much better than while on a keto diet (not to mention junk food diet)! I have more energy, my attention span has improved dramatically, and I’m feeling stronger emotionally and cognitively…though I’m often hungry or have an appetite for fruits and veggies, not junk food anymore. I guess snacking on healthy foods is better than junk food right?
I’m not cutting down in the amount of meat I eat though, just adding things in addition to it. I’ve never been a fan of “extreme diets’ like carnivore or veganism. I mean we need fruit and vegetables for certain nutrients that meats cannot provide, and vice versa. Some can do while others cannot as well. We have different genetics that makes certain diets better or worse depending upon the person.
I’m also not about cutting out certain foods (like some say to do with bananas due to higher sugar/calorie content) because again, they might be nutritious in ways other foods are not, plus limiting a banana to fewer times a week could be sufficient enough.
I had one doctor (the one who recommend a keto-meat rich diet) tell me to not eat fruit and very few vegetables, which I was shocked, and admittedly even a bit appalled by.
I have an appointment to speak with my doctor about the statins and tell her exactly why I refuse to take them unless there is a serious risk involved.