Jun 05

The Big Deal About Lipoprotein(a)

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.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:


Berglund, L. “Lipoprotein(a): An Elusive Cardiovascular Risk Factor.” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 12, Dec. 2004, pp. 2219–26. Crossref, doi:10.1161/01.ATV.0000144010.55563.63.
Gaubatz, J. W., et al. “Human Plasma Lipoprotein [a]. Structural Properties.” The Journal of Biological Chemistry, vol. 258, no. 7, Apr. 1983, pp. 4582–89.
van Buuren, Frank, et al. “Incidence of Elevated Lipoprotein (a) Levels in a Large Cohort of Patients with Cardiovascular Disease.” Clinical Research in Cardiology Supplements, vol. 12, no. Suppl 1, Mar. 2017, pp. 55–59. PubMed, doi:10.1007/s11789-017-0087-y.
Kotani, Kazuhiko, et al. “Evidence-Based Assessment of Lipoprotein(a) as a Risk Biomarker for Cardiovascular Diseases – Some Answers and Still Many Questions.” Critical Reviews in Clinical Laboratory Sciences, vol. 53, no. 6, Nov. 2016, pp. 370–78. Crossref, doi:10.1080/10408363.2016.1188055.
Nordestgaard, Børge G., et al. “Lipoprotein(a) as a Cardiovascular Risk Factor: Current Status.” European Heart Journal, vol. 31, no. 23, Dec. 2010, pp. 2844–53. Crossref, doi:10.1093/eurheartj/ehq386.
Langsted, Anne, et al. “High Lipoprotein(a) and Low Risk of Major Bleeding in Brain and Airways in the General Population: A Mendelian Randomization Study.” Clinical Chemistry, vol. 63, no. 11, Nov. 2017, pp. 1714–23. Crossref, doi:10.1373/clinchem.2017.276931.
Sawabe, Motoji, et al. “Low Lipoprotein(a) Concentration Is Associated with Cancer and All-Cause Deaths: A Population-Based Cohort Study (the JMS Cohort Study).” PloS One, vol. 7, no. 4, 2012, p. e31954. PubMed, doi:10.1371/journal.pone.0031954.
Faghihnia, Nastaran, et al. “Changes in Lipoprotein(a), Oxidized Phospholipids, and LDL Subclasses with a Low-Fat High-Carbohydrate Diet.” Journal of Lipid Research, vol. 51, no. 11, Nov. 2010, pp. 3324–30. Crossref, doi:10.1194/jlr.M005769.
Nilausen, Karin, and Hans Meinertz. “Lipoprotein(a) and Dietary Proteins: Casein Lowers Lipoprotein(a) Concentrations as Compared with Soy Protein.” The American Journal of Clinical Nutrition, vol. 69, no. 3, Mar. 1999, pp. 419–25. Crossref, doi:10.1093/ajcn/69.3.419.
10 Laron, Z., et al. “Insulin-like Growth Factor-I Decreases Serum Lipoprotein(a) during Long-Term Treatment of Patients with Laron Syndrome.” Metabolism, vol. 45, no. 10, Oct. 1996, pp. 1263–66. Crossref, doi:10.1016/S0026-0495(96)90245-0.
11 Wang, Xing Li, et al. “Acute Effects of Insulin-like Growth Factor-1 and Recombinant Growth Hormone on Liprotein(a) Levels in Baboons.” Metabolism, vol. 51, no. 4, Apr. 2002, pp. 508–13. Crossref, doi:10.1053/meta.2002.31328.
12 Ramharack, R., et al. “Dominant Negative Effect of TGF- 1 and TNF- on Basal and IL-6 Induced Lipoprotein(a) and Apolipoprotein(a) MRNA Expression in Primary Monkey Hepatocyte Cultures.” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 18, no. 6, June 1998, pp. 984–90. Crossref, doi:10.1161/01.ATV.18.6.984.
13 García-Gómez, Carmen, et al. “Lipoprotein(a) Concentrations in Rheumatoid Arthritis on Biologic Therapy: Results from the CARdiovascular in RheuMAtology Study Project.” Journal of Clinical Lipidology, vol. 11, no. 3, May 2017, pp. 749-756.e3. Crossref, doi:10.1016/j.jacl.2017.02.018.
14 Noma, A., et al. “Lp(a): An Acute-Phase Reactant?” Chemistry and Physics of Lipids, vol. 67–68, Jan. 1994, pp. 411–17.
15 Min, W. K., et al. “Relation between Lipoprotein(a) Concentrations in Patients with Acute-Phase Response and Risk Analysis for Coronary Heart Disease.” Clinical Chemistry, vol. 43, no. 10, Oct. 1997, pp. 1891–95.
16 Borba, E. F., et al. “Lipoprotein(a) Levels in Systemic Lupus Erythematosus.” The Journal of Rheumatology, vol. 21, no. 2, Feb. 1994, pp. 220–23.
17  Dursunoğlu, Dursun, et al. “Lp(a) Lipoprotein and Lipids in Patients with Rheumatoid Arthritis: Serum Levels and Relationship to Inflammation.” Rheumatology International, vol. 25, no. 4, May 2005, pp. 241–45. Crossref, doi:10.1007/s00296-004-0438-0.
18 Asanuma, Yu, et al. “Serum Lipoprotein(a) and Apolipoprotein(a) Phenotypes in Patients with Rheumatoid Arthritis.” Arthritis & Rheumatism, vol. 42, no. 3, Mar. 1999, pp. 443–47. Crossref, doi:10.1002/1529-0131(199904)42:3<443::AID-ANR8>3.0.CO;2-Q.
19 Silva, Isis T., et al. “Antioxidant and Inflammatory Aspects of Lipoprotein-Associated Phospholipase A2 (Lp-PLA2 ): A Review.” Lipids in Health and Disease, vol. 10, no. 1, 2011, p. 170. Crossref, doi:10.1186/1476-511X-10-170.
20 Kiechl, S., et al. “Oxidized Phospholipids, Lipoprotein(a), Lipoprotein-Associated Phospholipase A2 Activity, and 10-Year Cardiovascular Outcomes: Prospective Results From the Bruneck Study.” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 8, May 2007, pp. 1788–95. Crossref, doi:10.1161/ATVBAHA.107.145805.
21 Snyder, M. L., et al. “Binding and Degradation of Lipoprotein(a) and LDL by Primary Cultures of Human Hepatocytes. Comparison with Cultured Human Monocyte- Macrophages and Fibroblasts.” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 14, no. 5, May 1994, pp. 770–79. Crossref, doi:10.1161/01.ATV.14.5.770.
22 Aisina, R. B., and L. I. Mukhametova. “Structure and Function of Plasminogen/Plasmin System.” Russian Journal of Bioorganic Chemistry, vol. 40, no. 6, Nov. 2014, pp. 590–605. Crossref, doi:10.1134/S1068162014060028.
23 Laurens, N., et al. “Fibrin Structure and Wound Healing.” Journal of Thrombosis and Haemostasis, vol. 4, no. 5, May 2006, pp. 932–39. Crossref, doi:10.1111/j.1538-7836.2006.01861.x.
24 Weisel, John W., and Rustem I. Litvinov. “Fibrin Formation, Structure and Properties.” Fibrous Proteins: Structures and Mechanisms, edited by David A.D. Parry and John M. Squire, vol. 82, Springer International Publishing, 2017, pp. 405–56. Crossref, doi:10.1007/978-3-319-49674-0_13.
25 Loscalzo, J., et al. “Lipoprotein(a), Fibrin Binding, and Plasminogen Activation.” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 10, no. 2, Mar. 1990, pp. 240–45. Crossref, doi:10.1161/01.ATV.10.2.240.
26 Yano, Yoko, et al. “Immunolocalization of Lipoprotein(a) in Wounded Tissues.” Journal of Histochemistry & Cytochemistry, vol. 45, no. 4, Apr. 1997, pp. 559–68. Crossref, doi:10.1177/002215549704500408.
27 Oliveira, Catarina, et al. “Apolipoprotein(a) Inhibits Hepatitis C Virus Entry through Interaction with Infectious Particles.” Hepatology, vol. 65, no. 6, June 2017, pp. 1851–64. Crossref, doi:10.1002/hep.29096.
28 Bergmark, Claes, et al. “A Novel Function of Lipoprotein [a] as a Preferential Carrier of Oxidized Phospholipids in Human Plasma.” Journal of Lipid Research, vol. 49, no. 10, Oct. 2008, pp. 2230–39. Crossref, doi:10.1194/jlr.M800174-JLR200.
29 Kiechl, S., et al. “Oxidized Phospholipids, Lipoprotein(a), Lipoprotein-Associated Phospholipase A2 Activity, and 10-Year Cardiovascular Outcomes: Prospective Results From the Bruneck Study.” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 8, May 2007, pp. 1788–95. Crossref, doi:10.1161/ATVBAHA.107.145805.
30 Tsimikas, S., et al. “New Insights Into the Role of Lipoprotein(a)-Associated Lipoprotein-Associated Phospholipase A2 in Atherosclerosis and Cardiovascular Disease.” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 10, Oct. 2007, pp. 2094–99. Crossref, doi:10.1161/01.ATV.0000280571.28102.d4.
31 Lee, Kyuhyun, et al. “Adeno-Associated Virus-Mediated Expression of Apolipoprotein (a) Kringles Suppresses Hepatocellular Carcinoma Growth in Mice.” Hepatology (Baltimore, Md.), vol. 43, no. 5, May 2006, pp. 1063–73. PubMed, doi:10.1002/hep.21149.
32 Yu, Hyun-Kyung, et al. “Suppression of Colorectal Cancer Liver Metastasis and Extension of Survival by Expression of Apolipoprotein(a) Kringles.” Cancer Research, vol. 64, no. 19, Oct. 2004, pp. 7092–98. Crossref, doi:10.1158/0008-5472.CAN-04-0364.
33 Calmarza, P., et al. “Relationship between Lipoprotein(a) Concentrations and Intima-Media Thickness: A Healthy Population Study.” European Journal of Preventive Cardiology, vol. 19, no. 6, Dec. 2012, pp. 1290–95. PubMed, doi:10.1177/1741826711423216.
34 Tsimikas, Sotirios, et al. “Oxidized Phospholipids, Lp(a) Lipoprotein, and Coronary Artery Disease.” New England Journal of Medicine, vol. 353, no. 1, July 2005, pp. 46–57. Crossref, doi:10.1056/NEJMoa043175.
35 Langsted, Anne, et al. “High Lipoprotein(a) as a Possible Cause of Clinical Familial Hypercholesterolaemia: A Prospective Cohort Study.” The Lancet Diabetes & Endocrinology, vol. 4, no. 7, July 2016, pp. 577–87. Crossref, doi:10.1016/S2213-8587(16)30042-0.
36 Okuyama, Harumi, et al. “A Critical Review of the Consensus Statement from the European Atherosclerosis Society Consensus Panel 2017.” Pharmacology, vol. 101, no. 3–4, 2018, pp. 184–218. Crossref, doi:10.1159/000486374.
37 Thillet, J., et al. “Elevated Lipoprotein(a) Levels and Small Apo(a) Isoforms Are Compatible with Longevity.” Atherosclerosis, vol. 136, no. 2, Feb. 1998, pp. 389–94. Crossref, doi:10.1016/S0021-9150(97)00217-7.
38  “Lipoprotein(a) and All-Cause Mortality in Elderly Subjects: Data from the InChianti Study.” Nutrition, Metabolism and Cardiovascular Diseases, vol. 14, no. 5, Oct. 2004, p. 291. Crossref, doi:10.1016/S0939-4753(04)80094-2.

Leave a Reply

Photo and Image Files
Audio and Video Files
Other File Types
28 Comment threads
49 Thread replies
Most reacted comment
Hottest comment thread
31 Comment authors
Siobhan HugginsDaveRoger JohnsonRogerKaren Recent comment authors

newest oldest most voted
Notify of

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?


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):


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.


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.


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!!

Jak Mang
Jak Mang

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:


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!


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?


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!

Donald Lourie
Donald Lourie

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..


val wolf
val wolf

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.

val wolf
val wolf

Thank you Mike for the links. I will inform my Dr. about the Lp(a) study.

Michale Hartte

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?

Michale Hartte

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.


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)

#CholesterolScience Show – with Ivor Cummins » Cholesterol Code

[…] Blog post mentioned: The Big Deal about Lipoprotein(a) […]

Renee van der Touw
Renee van der Touw

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.


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?

Michael D Gartman
Michael D Gartman

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 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.


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,

Chad Spackman
Chad Spackman

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!!


–==== 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

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

AIP: -0.814 >>> Lowest Risk Third
Go to https://tinyurl.com/ycccmmnx for more on Atherogenic Index of Plasma

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

Jim O'Conner
Jim O'Conner

This may be of interest.


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”.

Mary Ellen
Mary Ellen

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


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?

Roger Johnson
Roger Johnson

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 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!