As some of you may know, I got the opportunity to present on the topic of Lipoprotein(a) for Low Carb Houston 2019. Just this past week the video was released, and is now available to view!
This can basically be thought of as an improved, fleshed out update of my Big Deal About Lipoprotein(a) post, so if you’re curious about my thoughts on lipoprotein(a) I’d recommend giving it a watch!
I also provide some data from some of my own experiments, including my pork versus beef experiment, and experiments showing lipoprotein(a) following LDL-C e.g. during the protocol.
As always, discussion is welcome especially as this is a topic that’s far from closed – there’s still plenty to learn and I look forward to doing so as more work is done to understand – the still quite mysterious – lipoprotein(a).
Hi Siobhan,
Thanks for your work. I see cross over in yours and Dave’s research with my own investigations of the literature. I believe there is sufficient evidence in the last 40 yrs of lipid research to suggest low LDL-C, via intensive therapy, can decrease the resilience of HDL to oxidative insults. In a high risk study population I think it is well demonstrated that endogenous MPO-cascade insults (associated with atherosclerotic burden) can damage apo E. As you note, apo E is recycled from early endosomes in hepatocytes and macrophages, and is transferred between TRLs and HDL in to maintain supply and demand post prandially – Apo E being essential to CM clearance via the liver.
Interesting regarding the MPO cascade – do you have a favorite paper that covers this? I haven’t come across that, but would read up on it with great interest. 🙂
Hi Siobhan,
Fav paper?…A substantial amount :). It’s one of a few pillars underlying 3 reviews i have written and thoroughly referenced. Oxidative insults (HOCl, VPO1 etc) first push apo E into dimers with themselves and with apo AII so as to protect vulnerable amino residues. This is maintainable as long as there are core antioxidants in the lipoproteins. Once antioxidants are consumed by the insult damage to apo E then begins. Note it’s the total of any antioxidants in all lipoproteins of shared locality to said insult – lipophillic antioxidants are caried by only a tiny subfraction of the HDL pool; a few HDL must protect all. It is further complicated by the ratio of tocopherols and carotenoids; enriching some more than others promotes lipoprotein oxidation (several studies in-vitro, one in-vivo in humans), and further HDL seems the most susceptible to this. I don’t have an academic institution behind the work, or funds sufficient to pay for peer review through say plos one or frontiers. Yet the papers are polished with all the references you seek properly associated. I’m more than happy to email them to you if you wish to read and follow the references down the rabbit hole :P. I’d appreciate the feedback actually. All the best
Sure, you can email them to siobhan.e.huggins@gmail.com if you’d like and I’ll be happy to read them when I get a chance.
Thanks Siobhan, I hope you find them interesting. I just sent them through to the above address…
Thanks I got them, I’m going to try and make room in my schedule to read them this week. 🙂
Would you please share a link to the study showing Lp(a)/CRP risks? Unfortunately it is not mentioned in the slides
Oh you’re correct – I usually try to make sure the title/doi is on the slide if I include a graph/quote from a paper. The paper in question is right here.
Intensive therapy may alter the portioning of dietary antioxidants into lipoproteins at the enterocyte through SREBP2/MiRNA33 induction, when combined with NPC1L1 & SRBI inhibition (ezetimibe) or antioxidant and cholesterol capture (bile sequesterants). I think i have demonstrated it is plausible that in clinical trials of high risk patients such inhibition may reduce resilience of HDL to MPO-cascade insults, resulting in increased apo E oxidation upon HDL2. This damaged apo E, preferentially transferred to CMs, could then result in increased CM remnant residence and the accumulation of VLDL1 behind them due to CMs hoarding LPL and HDL apos. Accumulating TRLs and the increased plasma FFA accelerates CETP transfers with HDL, causing HDLC catabolism (preferentially HDL2C). Increased VLDL1 residence directs more of VLDL into a remnant pathway rather direct clearance – ultimately increasing LDLC in the fasted state. Basically, the entire post prandial TRL metabolism cascade can be altered by just altering the positive to negative receptor ligand on CMs – of which oxApo E would be a double hit (and more if transfer seeded peroxidation). TRL remnants then evolve to be the trade partner post-prandially in place of HDL, (apo E & C’s move from preferential carriage in fasted state on HDL2 to VLDL remnants in hypertriglyceridemics). Further, the remnants have inactive LPL dimers and are apo E rich which draws CETP activity away from CMs (and a short intensive trade with them), prompting an extended scattershot of HDL CE trade with CMs through to IDLs.
I havent’ read the paper you showed about L(p)a, oxysterols and cancer; but in passing during my research I noted that cells taking up oxLDL have mitochondrial damage via oxysterols. I wondered, seeing that ectopic chain of F1-ATPase B1 is a HDL endocytotic receptor, why it takes in HDL and if dysfunctional/oxHDL may cause mitochondrial damage also…and if that could lead to cancer via Dr Thomas Seyfried’s metabolic theory of cancer? Does this protein, involved in ATP production; which spans the mitochondrial environment and beyond the cell membrane, draw in HDL in response to ROS, seeking HDL specific core-antioxidants like certain carotenoids? Or is it to receive instruction/update on the systemic energy stasis of the host via HDL carried MiRNAs? I noted how in SEAS trial of ezetimibe, there was a dramatic increase in cancer cases not seen in other ezetimibe trials which used high risk patients like ACS or kidney disease – phenotypes of known baseline HDL dysfunction. The SEAS population where normolipidemic aortic stenosis patients and so a completely different and arguably much less HDL ox stress at baseline. Seems reasonable that you won’t detect a change in cancer rate in a population where HDL can’t progress to markedly further dysfunction on-study… I haven’t investigated this at all, have written no papers on this point, I just think it’s another ‘interesting’ speculation 🙂 and deserves a closer look.
Hi Siobhan,
I’m curious your thoughts on a few things. I discovered at my annual physical, out of pure personal curiosity, earlier this year that I had high LP(a). No one….I mean NO ONE in my family has ever died “early” of heart disease, and actually neither my mother or father suffer/suffered (my mom passed from adenocarcinoma in 2017) with much beyond some elevated cholesterol levels and high blood pressure. My grandparents all lived well into their late 70’s/80’s on both sides of my family. My dad is still thriving at 73 and has even been a lifelong smoker who beat Prostate Cancer in 2015.
I had read an article about the Biggest Loser trainer and thought why not just check it. Mine came back at 296….I about gave myself a heart attack when I saw that. I never even suspected it would be elevated, but was truly just checking it as I’m kind of an information junkie.
So my questions are these:
I am picking up a Boston Heart test today that I will be having done over the next couple of weeks and I want to be sure to set myself up for true results as this has been something that has worried me ever since I saw the results.
THANK YOU for all of the work that you and Dave are doing around this and all of the Lipid work.
Hi, Tyann – it’s always worth noting that I’m not a doctor and can’t give medical advice, but can share my thoughts in case they’re of interest.
Anecdotally, yes, although to stress it is anecdotal. I’ve seen a few people here and there surprised they have high lp(a), and that they can trace it to one or both parents, with no family history of early heart disease/MI on the carrier side, including one of my parents and their family. But, there may be other factors at play, so I’d want to be careful given how much is unknown.
I’d much prefer a study looking at genetically high lp(a), in metabolically healthy people (e.g. non-hyperinsulinemic), looking at outcomes in that context to clarify what may be going on – but I haven’t seen that yet. Data over anecdote is my preference, and I discussed much of the available data in the presentation and posts here suggesting context may play in. But, it’s not definitive – I’m cautiously optimistic to be sure, but constantly looking for anything that may give me pause on that view.
If it were a family member inquiring – I’d want them to look at all the available evidence, on both sides, and come to their own conclusions about what they’re comfortable with. Sam Tsimikas for example is a great resource for a more “pessimistic” perspective. He’s been interviewed on Peter Attia’s podcast regarding lp(a) which might be a good place to start if you want to explore other perspectives.
I’ve not seen it come up and I’ve not personally tested this myself – it’s possible. I’ve just not seen anything on it, personally, anecdotally, or in the literature (but there are a lot of areas where lp(a) still needs to be explored).
Correct. The data regarding lp(a) we have does indicate that it’s an acute phase reactant, and the highest lp(a) I have on record is a bit after getting sick with a fever. I’ve also seen it bump up a bit from other minor illnesses as well. Likewise, when I recover and am asymptomatic again, it comes back down to my “normal”. So, if I were you, and I suspected that might be the case, I’d likewise want to follow-up when I’ve recovered and am well again and see if that might have confounded the prior test.
That said, as mentioned in the presentation, metabolism can also play into levels. So, as with any metabolically influenced marker, I’d want to be sure to eat to my normal for the week leading into the test (normal amount/not eating more or less than usual, normal food, etc), fast for 12-14 hours water only (no coffee, no caffeine, no tea), and be sure I am not sick with something when re-testing to avoid any potential confounders on those fronts.
Hope that helps!
Hi Siobhan
I was thinking of taking a lipid and Hba1c test again before and after.
I know that my cholesterol numbers are bad as per the doctor.
I would like to replicate the diet that Dave Feldman did from 9-20-18 thru 9-26-18 to drop his numbers from 296 to 83.
His video talk said he had white bread, processed meat and some supplements. I was wondering if you could help me by letting me know exactly how much and what he ate and at what times to have his numbers change in just a matter of days. I am just concerned that my Hba1c would go up.
Thanks for your time.
George
Hi George, as discussed I did pass this on to Dave and he said he’d follow up with you. If you don’t hear back from him soon please do reach out so I can ping him on it. 🙂
hi Siohban, I’d like to know your opinion about what is going on with me, if possible. I’ve been struggling all my life wiht POS and IBS… wondering from one doctor to an other with no success. Around Sept. 2019 I decided to make my own investigation… I’m not a doctor, just an Argentinean marketer tired of feeling bad.
I started gradually making some changes in my diet. I’m thin, so I didn’t focus in my weight… just my habbits… like oils that I use, cutting sugar and refined carbs.. then grains followed and I started to feel much better. So I continued with some intervals, until finally staying keto/LCHF since August 2020. I don’t count macros, but I’m feeling better than ever and gradually started eating only one or two times a day.
On september 2020, I had Covid… luckily with no complications, just felt extremely tired. then in October I decided to make a test and there begun my second race to finding a doctor that didn’t collapse by seeing my lipid panel. I went to a cardiologist, did several tests and everything was normal (didn’t have a CAC test, didn’t know about it and the doctor didn’t ask for it).
So, my TC 288, HDL 79, LDL 194 TG 73. I was anemic with low hemoglobin 11.2 g/dl and ferritin 4ng/nL.
Had to change doctors… all prescribed statins and iron…
Now I had re checked my labs and found my CT 351, HDL 92, LDL 248, TG 56.. I was happy with this, but found out some other things that made me uncomfortable:
LP(a) 281 nmol/l, PCR 1,04mg/l, prolactin 53,8ng/ml, T3L 1,62 pg/ml, T4L 0.85 ng/dl, THS 2,26 μUI/mL and ty antibodies ATPO 135 UI/ml.
No family history of hart attack.
Can you give me your opinion? should I worry? I have a consultation with another doctor next week and I’ve been investigating on this, but again.. I’m not a doctor and really want to understand and improve my health.
Thank you very much
Jimena.
Question is: you worry about what? Heart attack? Then do a CAC and check it’s progression in time. How about inflammation – any CRP readings?
Hi Jimena –
A few points to address here. First, we’re not doctors and can’t give medical advice, so we can only provide our thoughts in case they may be of interest.
Regarding your lipid profile, it looks like you fit the profile of a Lean Mass Hyper-responder e.g. someone who is typically lean, active, and powered by fat (e.g. on a low carb/ketogenic diet). You may be interested in the Lean Mass Hyper-responder facebook group as there are many there with similar profiles who explore the latest research regarding it, their experience, their perspective, and how they’ve approached having the profile (e.g. taking steps to move away from the profile and how they did so, sticking with it but getting additional testing to keep an eye on things, etc).
We can’t say whether this profile is of concern or not (again we’re not doctors), but we can offer some resources to explore different perspectives on the topic. For example there’s this presentation from Dave looking at high LDL in the context of high HDL and low triglycerides from a cautiously optimistic perspective, plus this post from Dr. Nadolsky looking at the same topic from a cautiously pessimistic perspective.
As for the lipoprotein(a), I believe I summarize my current thoughts on the marker in the presentation linked in this post. I can’t say anything definitive regarding it, whether one should worry or not, or should or shouldn’t take action on any given number. I’m not a doctor, and I personally think it is a personal decision. Like cholesterol in general, what I did in a similar situation was to look into thoughts on both sides and decide how I felt about the number. Obviously my presentation presents one perspective, and for a differing perspective Sam Tsimikas has had many discussion on the topic via twitter. In his pinned tweet there are many comments he’s made linked for ease of access.
Regarding the other markers, I am not as familiar and likely your doctor would be able to help you interpret the results. For thyroid markers there is also Stop The Thyroid Madness which is a website I often see recommended for information on thyroid numbers. They have a post on interpreting various values here. Perhaps that would be a helpful resource if wanting to investigate further with your doctor if you both decide it is warranted.
Great presentation Siobhan! I just wanted to share my own personal experience with LP(a) which is that it is not static, at least not for me. I’ve gone from 191 to 45 and although I cant say with certainty as to what brought it down I can say that I suspect that it was my diet. In 2019 LP(a) was 170 on a paleoish type of diet. A few months later it was 191 during my brief period on statins and then without statins and slowly moving from keto to carnivore over the last year I’ve watched it drop all the way to 45. I’ve been on the hunt to find out why I had non 0 cac score a few years back and LP(a) has been one of my suspects. Thanks again!
Thanks for sharing your experience, Greg! Always interesting to hear about others who have found lp(a) shifting from diet/lifestyle under different contexts.
How bad are my levels please? 31 male none smoker, exercise daily, high protein diet.
Total Cholesterol – 204.95 mg/dl
HDL – 54.14 mg/dl
LDL – 131.48 mg/dl
TRIG – 88.57 mg/dl
Non HDL – 150.8 mg/dl
ApoA1 – 120mg/dl
APOB – 104mg/dl
APOB:APOA Ratio – 0.8
PL PLA2 – 520 U/L Range –
or equal to 635 U/L – High Risk
LP(a) 160 nmol/l
CRP-hs – 1.3 mg/dl. ( usually 0.5) I have IBS stomach issues / pain lately
How bad are my levels please? 31 male none smoker, exercise daily, high protein diet.
Total Cholesterol – 204.95 mg/dl
HDL – 54.14 mg/dl
LDL – 131.48 mg/dl
TRIG – 88.57 mg/dl
Non HDL – 150.8 mg/dl
ApoA1 – 120mg/dl
APOB – 104mg/dl
APOB:APOA Ratio – 0.8
PL PLA2 – 520 U/L Range –
or equal to 635 U/L – High Risk
LP(a) 160 nmol/l
CRP-hs – 1.3 mg/dl. ( usually 0.5) I have IBS stomach issues / pain lately
Hi Dave,
We can’t say whether any given profile is of concern or not (as we’re not doctors and can’t give medical advice), but we can offer some resources to explore different perspectives on the topic. For example there’s this presentation from Dave looking at high LDL in the context of high HDL and low triglycerides from a cautiously optimistic perspective, plus this post from Dr. Nadolsky looking at the same topic from a cautiously pessimistic perspective.
You may also be interested in this post regarding apoB, as well.
I’ve also run your numbers through our report tool which you can see below: • • • Cholesterol Rx: false •
–===== CholesterolCode.com/Report v0.9.5.15 =====–
• Male • 31 • Coffee:
•
•
Total Cholesterol: 205 mg/dL 5.3 mmol/L
LDL Cholesterol: 131 mg/dL 3.39mmol/L
HDL Cholesterol: 54 mg/dL 1.4mmol/L
TG Cholesterol: 88 mg/dL 0.99mmol/L
———RISK REPORT———
Atherogenic Index of Plasma: -0.15 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: >>> Medium Risk Third
—-> Go to https://tinyurl.com/y63xp7lj for more on the Jeppesen study
Cholesterol Remnants: 20 mg/dL >>> 0.2 mmol/L >>> Low Risk
—-> Go to https://tinyurl.com/y84u92wm for more on Cholesterol Remnants
——CONVENTIONAL MARKERS AND RATIOS——
Friedewald LDL-C: 133 | Iranian LDL-C: 131
TC/HDL Ratio in mg/dL: 3.8
TG/HDL Ratio in mg/dL: 1.63 | TG/HDL Ratio in mmol/L: 0.71
———OUR COMMENTS———
**This does not constitute medical advice**
• Your triglycerides of 88 mg/dL are typically considered optimal.
• We would consider your HDL of 54 mg/dL as strong.
• Your LDL cholesterol of 131 mg/dL is close to the average for the general population.