ApoB: Is Lower Always Better?
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- čas přidán 27. 06. 2023
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Papers referenced in the video:
The association of apolipoproteins with later-life all-cause and cardiovascular mortality: a population-based study stratified by age
www.ncbi.nlm.nih.gov/pmc/arti...
Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis
pubmed.ncbi.nlm.nih.gov/32203...
Serum lipid traits and the risk of dementia: A cohort study of 254,575 women and 214,891 men in the UK Biobank
pubmed.ncbi.nlm.nih.gov/36247... - Věda a technologie
We know that people with diseases have low LDL. This could be true for Apo B as well. APOB could be low because of ill health not the other way around.
Yep, definitely
That's why he called it "associated"😁
This is the argument I heard about those lower deciles/quartiles/whatever having higher mortality as well. It def makes me a little nervous since I'm targeting very low LDL (like 60-70mg/dl) though.
That's for 60 year old and above.
@@neilquinn I don't think it obtains if you lower your cholesterol with diet and/or statins. I think this applies only to people who have low cholesterol due to some illness.
A very thought provoking video. Since both LDL and ApoB are composite markers covering a range of different lipid particles, we are seeing different effects becoming more prominent at different ages. In younger populations, the problem seems to be system reaction to oxidative stress, inflammation and other underlying issues. In older age groups something else is becoming more important. I would guess hypo-function and malabsorption.
Very low APO B May correlate with individuals that are on high statin therapy due to past CVD and thus skews the results
Yes, that's possible, that was a limitation mentioned in the paper
Do you believe statin therapy is good as long as APO B doesn't fall too low?
@@KoiRun50 If the goal is to reduce LDL (and ApoB), I think dietary change is the best was to reduce it, relative to statins.
Would love for you to explore the dietary approach to healthy lipid levels!
@@Vested_Investor
Eliminate:
trans fats
Decrease:
- simple carbs & sugars
- saturated fats
Increase:
- soluble fiber
- polyunsaturated fat & polyphenols from minimally processed foods (eg nuts)
- probiotic (lacto-fermented) foods
Fantastic explanation and charts. Thanks
Thanks @startingtoday4663!
All these U-shaped curves in epidemiological studies may just mean that there may be other factors for the people at the lower end of the spectrum, like serious illnesses, that as a side effect bring these levels too low. That would be irrelevant to a healthy individual with a "too low" ApoB.
Yep, definitely, that can be the topic of another video, but the idea that's circulating online that lower ApoB is always better for health may not be true, especially when it comes to all-cause mortality risk in people older than 60y. Prior to this video, I hadn't see that info on the interwebs...
@@conqueragingordietrying1797 Those who say "lower ApoB is always better" probably don't mean that ApoB should be as close to 0 as it can for the perfect health. 🙂 But I'd guess for the real risk ApoB should be significantly less than 0.8 g/L. At least my Labcorp test report recommends to lower ApoB to less than 70 mg/dL. My last reading was 118 and LDL-C 172. I was considering a statin, but according to your explanation I am perfectly fine, right?
@@maestroharmony343 That’s not for me to decide, I’m just presenting the published evidence so that people can make informed decisions with as much context as possible.
APOB- B is not always u-shaped. Lower APOB was linearly associated with lower all cause mortality in this study when adjusted for
(1) malnutrition (table C) or (2) covariates: age ≥75 years, sex, PCI and comorbidities including AMI, CHF, hypertension, diabetes mellitus, CKD, anemia, atrial fibrillation, COPD, stroke and malnutrition (table D). See Figure 5.
Li H, Wang B, Mai Z, Yu S, Zhou Z, Lu H, Lai W, Li Q, Yang Y, Deng J, Tan N, Chen J, Liu J, Liu Y, Chen S. Paradoxical Association Between Baseline Apolipoprotein
I get the feeling that Dr. Carvalho would say that Lower (within normal ranges) may always be better and that perhaps we also have reverse causation here. Dr. Carvalho covered cholesterol, BMI, Blood Pressure and obesity paradoxes in yesterday's video below. Perhaps he would also say that there is a similar explanation for an Apob paradox.
czcams.com/video/a3lHHnOHyr8/video.html
Thank You!!!!!
It makes sense that since each LDL/VLDL etc has 1 and only 1 ApoB protein wrapped around it...if your ApoB is TOO low, it probably means that you aren't making enough cholesterol to keep up with the energy demands of the body, which could explain the increased all cause mortality risk since you need adequate cholesterol for your vitamins, hormones, etc.
Lower APOB was linearly associated with lower all cause mortality in this study when adjusted for
(1) malnutrition (table C) or (2) covariates: age ≥75 years, sex, PCI and comorbidities including AMI, CHF, hypertension, diabetes mellitus, CKD, anemia, atrial fibrillation, COPD, stroke and malnutrition (table D). See Figure 5.
Li H, Wang B, Mai Z, Yu S, Zhou Z, Lu H, Lai W, Li Q, Yang Y, Deng J, Tan N, Chen J, Liu J, Liu Y, Chen S. Paradoxical Association Between Baseline Apolipoprotein B and Prognosis in Coronary Artery Disease: A 36,460 Chinese Cohort Study. Front Cardiovasc Med. 2022 Jan 25
Great comment
I love your videos.
Thanks @haroldpierre1726!
It is most probably a reverse causation, similar to the case with LDL cholesterol. The median ApoB levels in children are lower at 0.75-0.8 g/L.
Yep, that’s probably true. Nonetheless, the idea that lower ApoB is always better may not be true, assuming reverse causation isn’t involved.
@@conqueragingordietrying1797except based on the preponderance of the evidence (RCTs, MRSs,) we know that reverse causation almost certainly IS involved, which is why this video is misleading.
@@Seanonyoutube There's no intent to mislead. Sure, we can assume reverse causation, which may or may not be true, but we'll have to wait for studies to show that for ApoB, as it wasn't addressed in the paper.
@@conqueragingordietrying1797 no, we don’t need to wait for studies showing that for ApoB. LDL-c is a good enough correlate. ApoB is just a little more precise as it encompasses all atherogenic particles. Btw, this U shape curve with ACM can be seen in many other markers besides LDL-c, including obesity, A1C, and blood pressure. And yet you wouldn’t in your right mind recommend that perhaps someone is better off being pre diabetic or hypertensive, would you? So why are you doing it with lipids?
@@Seanonyoutube The premise that is out there is that lower ApoB is always better. Based on the data in the video, that may not be true-all I'm doing is adding context to the ApoB story. To ignore it or not know about the association in the video, or to try to explain it with reverse causation (where's that published evidence for ApoB?) doesn't make it right, either. Now we can at least finally have that discussion, as I'd yet to see the study in the video discussed anywhere online.
I'm not suggesting to raise ApoB, I'm just presenting evidence that disagrees with the lower is always better premise. What people choose to do with that info is up to them.
Very fascinating how it is associated with higher all cause and cardiovascular mortality in younger individuals than lower individuals. I wonder if there could be a confounding or multiple confounding variables at play that may skew the data to the left.
Yep, it could be reverse causation. More studies are definitely needed, as this is the only one that I found for all-cause mortality risk in the general population.
Maybe you can pull data from the Mendelian randomization studies of apoB and do some math on it? That might provide the better understanding of causality.
The CHD study in comparison with LDL is based on MR...
Wow, it seems like there's endless quantity of longevity variables and you are handling all of those!
Trying to handle them all, Vedran-I'm serious about Conquering Aging or Dying Trying!
Thanks for the video. Interesting subject, modern medicine seems not interested. Thanks for your never ending insight!
Very nice analysis, thank you for putting this together! Is there a video in the future about "LP(a): Is Lower Always Better?"
Thanks @combiner008. I can definitely do that, and I track it on every test, too.
When I've seen this discussion before on yt, the argument has been that lower ApoB in older people is associated with cancer. So of course there's going to be a higher mortality rate.
I don't dispute that, but prior to this video, I'd yet to see/hear that lower ApoB may not always be better for health.
@@conqueragingordietrying1797it’s literally the most common argument circulating all over social media within the “cholesterol skeptics” community who don’t understand how to read or interpret scientific data…
I'd like to hear your take on lp(a) as well sometime - esp with the fact that statins actually can modestly increase it!
Truth nuggets. ....
Great video Michael! Are the foods that lower LDL the same foods that lower ApoB? Did you do any food correlations for those of us under 60 with a high hereditary risk of heart disease based on your ApoB data? Thank you.
Thanks Bob. I haven't done that analysis, but probably yes, as most ApoB is coming from LDL. With that in mind, very high fiber diets reduce both ApoB and LDL:
pubmed.ncbi.nlm.nih.gov/11288049/
Do any of these studies that show the U-shaped hazard curve address reverse causality? There are conditions that increase mortality which reduce non-HDL blood cholesterol and therefore apo-B.
They didn't in that study, but that's a good point, they should've accounted for reverse causality.
Exactly! Reminds me of studies on sleep and mortality, where there's also a U-shaped hazard curve. That U-shape is likely because sick people sleep more, and sickness is associated with mortality obviously. It's not that sleeping 9+ hours is unhealthy, but rather that unhealthy people require 9+ hours of sleep. I suspect there's a similar situation with HDL cholesterol and ApoB.
We would have to look at some randomised control studies.
Question. You mentioned that HR of 1.4 was stat significant vs LDL in the first graphic. I agree. However an HR of 1.4 is not a stat significant in itself because to find the study meaningfull you would need to reach an HR>2 according to stats. This is the reason thousands of studies are meaningless. What do you think?
@@bobbobson4030 Most RCTs for ApoB lowering are in CVD patients, so I don't think that studies exist for ApoB lowering in the general population...
WOW😮!!! I was so proud of my last blood work numbers on ApoB. I’m 60 yrs old and my ApoB was 1.03g/l . Now I have to rethink my diet to get that marker up. Thanks for your insight and dedicated work to show us the right markers.
Please don’t raise your ApoB. That’s absolutely a dangerous conclusion and why Michael should remove this video. Lower Apo-B (within the physiological range) is almost certainly always better. We know this from the numerous higher quality studies examining causation of atherosclerosis and mortality.
Remove the video? I've presented evidence that lower may not always be better. If people choose to make decisions based on the published evidence, that's their decision. Either way, I'm not encouraging people to raise their ApoB, that's not stated anywhere in the video.
ApoB is not just involved in atherosclerosis, and it's possible that reducing risk for 1 outcome increases it for others. For example, in this study (bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0976-4), relatively higher ApoB was indeed associated with a higher myocardial infarction risk, but was also associated with a lower breast cancer risk. We should be looking at associations for ApoB with all-cause mortality, not focusing only on atherosclerosis, in order to minimize all risk, not risk just for 1 outcome.
@@conqueragingordietrying1797 you most certainly did NOT present evidence that lower may not always be better. You presented evidence that there is some unclear relationship between very low Apo-B and mortality in the elderly. To suggest that it is even remotely possible that the low Apo-B is the CAUSE for said higher mortality is to ignore all the other, higher quality evidence we have on the topic. In the Mendelian randomization studies looking at cohorts with ultra low ApoB from birth, we do NOT see any increase in mortality due to other diseases. Stop burying your head in the sand dude.
Lower may be better! Lower APOB was linearly associated with lower all cause mortality in this study when adjusted for
(1) malnutrition (table C) or (2) covariates: age ≥75 years, sex, PCI and comorbidities including AMI, CHF, hypertension, diabetes mellitus, CKD, anemia, atrial fibrillation, COPD, stroke and malnutrition (table D). See Figure 5.
Li H, Wang B, Mai Z, Yu S, Zhou Z, Lu H, Lai W, Li Q, Yang Y, Deng J, Tan N, Chen J, Liu J, Liu Y, Chen S. Paradoxical Association Between Baseline Apolipoprotein
I ran a little low myself at 48 mg/dl, so I did my own 5 minutes worth of research. My conclusion: I don't need to raise my APOB.
@@jackbuaer3828 *in CVD patients...What about the general population who does not have CVD? afaik, only 1 study for all-cause mortality risk.
It would be interesting to see All Cause Mortality risk versus both ApoB and HDL simultaneously. The Framingham Heart study showed high HDL was protective and resulted in a hazard ratio less than 1 for all levels of LDL.
Michael: Here’s something I don’t think I’ve seen discussed. In this example, low ApoB for >60 y.o. is significantly associated with ACM. On the other hand, if the average of one’s biological clock ages is in the 40’s (range = 35 to 51) which age group of ApoB populations do you suppose would apply?
When considering that ApoB is relatively low in youth, in conjunction with the youthful biological age, it may be an example where an epidemiological association for increased mortality risk doesn't apply at the individual level.
@@conqueragingordietrying1797 Thanks, that makes sense. It seems that individuals who engage in age-deceleration need to overlay study findings with their personal variables before reaching conclusions. Someday an AI will do this for me, and I can leverage that to do n=1 food and exercise experiments the way that you do.
Modern epidemiology does not rely on measures of statistical "significance" (p values, overlapping confidence intervals, etc.) to determine whether or not there might be a meaningful association between a risk factor and some clinical outcome.
Thanks, as always, Michael. Why is this not part of our yearly bloodwork for our annual physical then?
Thanks @johntaylor7952. I'm not sure, as ApoB is relatively cheap. To get around it, one can approximate ApoB levels with the sum of non-HDL cholesterol.
Doctors aren't following the newest research.
"The 2018 American College of Cardiology/American Heart Association guideline for the management of blood cholesterol has recommended apo B as a risk assessment enhancer for individuals with intermediate atherosclerotic cardiovascular disease (ASCVD) risk when evaluated with traditional risk factors. The 2020 European Society of Cardiology and the European Atherosclerosis Society guidelines have ranked apoB as the most accurate marker representing atherogenic lipoproteins for predicting cardiovascular risk."
Please translate ApoB in g/Lt to Quest's mg/dL - is just a matter of moving the decimal point a couple of spaces to the left?
Yes. 1g/l = 100mg/dl
What is your opinion Apo(a) vs Apo(b)?
Could you give me the URL of the APO-B reference. Thank you. This reference seems to refute a lot of videos Dr Attia with has made with research doctors about the positive effects of lower APO-B
It's in the video's description, at the bottom
Lean people who do not eat a lot of carb/sugar will have higher APO B but in context they also DON’T have high inflammation, high BP, high A1C. So why higher APO B? Easy, because they are burning more fat for fuel and APO B carry the energy to the cells that need it.
@karend.9218 Thanks, this is interesting as I was just looking into this topic but couldn't find much on it. Could you share any relevant links to more information / research that explains this further, or provides more details around this line of thinking? Would be appreciated!
In cases where optimal ranges for a biomarker depend on the individual's age, would you take into account the chronological or the biological age? Like, for example, if I were 60 years old but my biological age were calculated to be 50, should I aim to stay in >=60 y/os' optimal range, or
Chronological, but within the context of other biomarkers. For example. ApoB is not associated with mortality risk in 39-59y, probably in part because low ApoB within the context of other youthful biomarkers is a part of the youthful phenotype.
However, low ApoB at older ages, in conjunction with other aged biomarkers is a part of the aged phenotype, which is bad for health.
In other words, if older than 60y, and with low ApoB, I'd aim to make as many other blood biomarkers as youthful as possible-high albumin, HDL, and lymphocytes, for example.
Thanks Michael. Wondering the biological reason for lower apoB increases the risk for above 60?
Cholesterol aids a declining immune system, but eventually the liver can’t make enough…
Are these results corrected for diseas? Is it only from otherwise healthy people? Nutrition Made Simpla channel just uploaded "Cholesterol & Risk of Death | New Evidence Emerges" where he goes through why it might look like optimla cholesterol levels would be higher than recommended due to this factor. If you are sick and frail a lot of values might drop, skewing the statistics if we don't account for it.
The data in the video included adjustment for age, sex, and baseline history of CVD
@@conqueragingordietrying1797 Thank you for your reply and your work. So only CVD. In that case I would be hesitant to draw to strong conclusions unless there is something I missunderstod. I guess they summarize it here:
"The reason behind such a paradoxical association is not entirely clear. It is possible that the age difference represents selection, so that individuals susceptible to high cholesterols already died before reaching older ages, and those who survived to be included in the study are likely to be less influenced by high cholesterol. Moreover, it has been proposed that in old age TC is a marker of general health, rather than a marker specific for CVD risk15,16. However, our results do not suggest that older individuals with higher TC and LDL-C cannot benefit from lipid-lowering treatment. According to the 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice, lipid-lowering treatment is recommended for older adults with a history of CVD in the same way as for younger adults, and in healthy people ≥ 70 years, lipid-lowering treatment shall still be considered if at high risk or above according to specific risk scores24. We also found that the lowest TC and LDL-C levels were associated with higher mortality in all the age groups. Cholesterol is important for many body functions including brain metabolism and intracellular transport, and very low cholesterol could increase the susceptibility to cancer, hemorrhagic stroke, or fatal diseases with infectious origins, such as respiratory and gastrointestinal diseases25-27."
But, couldn't it be that the increased ACM on the lower end of ApoB be a factor of epidemiological data, similar to LDL, wherein it is associated with other disease states? Still seems the most actionable/ generalizable thing here is to just take steps to lower your ApoB no matter who you are, no?
Yep, definitely, that can be the topic of another video, but the idea that's circulating online that lower ApoB is always better for health may not be true, especially when it comes to all-cause mortality risk in people older than 60y. Prior to this video, I hadn't see that info on the interwebs...
@@conqueragingordietrying1797 Got it. Appreciate your work! Focus on apoB allowed me to back it down 10 points to 72, best in 2 years of tracking. So I appreciate that you and other investigate these topics and share findings!
isn't that just because different diseases get too big of a confounding factor when you get too old? There are many diseases (most notably probably cancer) which cause Cholesterol/ApoB drop at a certain age.
Yep, co-morbidity at older ages is a likely reason for why low ApoB is associated with an increased risk. In that case, decreased liver function-->lower production of ApoB-containing lipoproteins, which are known to decline during aging (LDL, for ex.)
@@conqueragingordietrying1797 do you think that makes lowering ApoB less relevant among the elderly?
1.24g/L … 124mg/dl of apoB is really high … I’m shocked … I’m betting this would im9,y an ldlc of around 150-160 as mentioned in this chat, my thoughts would go to diseased states sucking in cholesterol. Def need more mechanistic data …
Seems wrong but I completely believe your data, I’m wondering “why” low apoB > 60yo had a higher risk profile .. it’s clearly not CVD … is this a case of ashtrays and cancer ?
It could be lots of things, but most likely is reverse causation, i.e. sicker people have lower ApoB. Whether that's cause or consequence, though...
@@conqueragingordietrying1797 so - it begs the questions - it is a good idea to optimize to potential disease state blood markers .. not just ldlc or apoB but any of them -?
This is a good video. Thanks! I have been critical of a few of yours from a clinical perspective. Particularly, you might recall on the use of CRP.
Why is it that many Lipidologists promote pushing Apo (b) down to below 0.8. The health influencer Peter Attia promotes driving it to below 0.5. Are there large studies that suggest there is clinical long-term benefit to this approach. It would seem like everyone should be on medications if thats the case.
czcams.com/video/d9pvsjPVcSk/video.html
That's because ApoB is almost the same as LDL, it's just to sell more tests. If your ApoA1 is higher than 160 mg/dL you might live a long time, all the other cholesterol tests are less important.
Sorry to say, this video is misinformation, because he makes too swiping and incorrect conclusions from an association study. As @greggbambu411 correctly points out. "We know that people with diseases have low LDL. This could be true for Apo B as well. APOB could be low because of ill health not the other way around."
There is no misinformation in the video. The video's premise is, Is lower ApoB always better? If you're older than 60, *maybe* (emphasized in the video!) not, especially in terms of all-cause mortality risk. That's based on published evidence, not misinformation.
Lower may be better for healthy people.
Lower APOB was linearly associated with lower all cause mortality in this study when adjusted for
(1) malnutrition (table C) or (2) covariates: age ≥75 years, sex, PCI and comorbidities including AMI, CHF, hypertension, diabetes mellitus, CKD, anemia, atrial fibrillation, COPD, stroke and malnutrition (table D). See Figure 5.
Li H, Wang B, Mai Z, Yu S, Zhou Z, Lu H, Lai W, Li Q, Yang Y, Deng J, Tan N, Chen J, Liu J, Liu Y, Chen S. Paradoxical Association Between Baseline Apolipoprotein
I posted this in a couple of places in comments here, just so the other commentators would see it.