Easy Hacks Guide Targeting Different Biomarkers (BMI, apoB, blood pressure, HbA1c, eGFR, etc)

#1

I’m trying to figure out if it would be good to use good medicines or hacks for different biomarkers or markers at a certain point when they go out of range and cease use if they stay at optimal range.

It’s basically the solution for every biomarker becoming problematic.

BMI

For example, might using a GLP-1 agonist like Zepbound (Tirzepatide) or Ozempic (Semaglutide) recommended to try to use at a certain BMI level? For example above BMI 22, or what would be the optimal BMI level to start using a GLP-1 agonist?

BMI at 22 is around the optimal range for associative ACM, that’s why I’m wondering as an algorithm it would be recommended to be started above 22. It can be discontinued at optimal BMI and reintroduced if BMI drifts from the optimal range.

ApoB

Lipids, for apoB we have Lipitor (Atorvastatin) or Crestor (Rosuvastatin). As well Zetia (Ezetimibe), Bempedoic Acid, and PCSK9 inhibitors. Anything above 70 mg/dl is certainly suboptimal, and lower is better. Since so few can be below 5th percentile by definition that means constantly on medication and no cessation, only replacement.

Blood Pressure

Optimal seems to be as low as possible as long as there is no fainting or side effects, might be important for elderly to especially have not too low BP or get close to it for falls. But below 120/70, telmisartan seems good for this.

HbA1c

We have Jardiance (Empagliflozin) and Forxiga (Dapagliflozin). I don’t know the optimal level here but at least below 5.7% seems optimal.

eGFR

We can use Jardiance (Empagliflozin), Forxiga (Dapagliflozin), GLP-1 agonists that don’t affect weight as much like exanetide and dulaglutide. Higher than 90 mL/min/1.73m2.

hsCRP

Lower is better, it’s possible to use statins like Lipitor or Crestor, as well as GLP-1 agonists.
The full Wiki page for CRP is here: Optimizing Guide for CRP (hsCRP)

So to sum the current biomarkers we now have…

BMI: Zepbound and Ozempic. Optimal BMI 22.
ApoB: Lipitor, Crestor, Zetia, Bempedoic Acid, and PCSK9 inhibitors. Lower than 70 mg/dl, probably much lower.
Blood Pressure: Telmisartan. Below 120/70, as low as possible without side effects. Careful about falls in elderly.
HbA1c: Jardiance, Forxiga. At least below 5.7%.
eGFR: Jardiance, Forxiga, Exanetide, and Dulaglutide. Target above 90 mL/min/1.73m2.
hsCRP: Lipitor, Crestor, Exanetide, Dulaglutide. As low as possible.

Feel free to add other biomarkers, comments on when to initiate or cease a treatment. There is also a case of using some of these drugs without being out of optimal range, like GLP-1 agonist for other diseases.

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Optimizing Guide for CRP (hsCRP)
Optimizing Guide for CRP (hsCRP)
There are likely about 18,000+ Rapamycin Users in the USA Now
#2

eGFR should be added (> 90 mL/min/1.73m2). Treated with SGLT2i and/or GLP-1RA. If needed, some GLP-1RAs also don’t affect weight as much (exenatide, dulaglutide).

In the future (once we have drugs to treat it): Lp(a).

Also: hsCRP? (with statins? GLP-1RA?)

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#3

I made it a wiki now so other people can edit it.
It could become a useful post to get fast info on some possible hacks.

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#4

Good idea but I think we should split that in individual topics with that one as the master and links to each topics/discussions so that the discussions can stay focused and not all over the place.

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#5

Actually this is a pretty good idea, and I agree with the biomarkers and their targets. Also, the interventions are appropriate. Great guide so far! :+1:

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#6

I’ve made a first wiki page for hsCRP here Optimizing Guide for CRP (hsCRP)
It’s linked from the wiki page above. We need specialized wiki pages otherwise it’s going to be enormous and the discussion will be all over the place.

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#7

Wonder if this one should be based on visceral or overall fat mass and not BMI. One can get from DEXA.

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#8

Do you have a sense of they help raise this also from good (to optimal) levels - or just if the levels are low/impaired?

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#9

eGFR (not a great metric on balance) must be adjusted for age and, eventually, muscle mass and perhaps other factors. The higher the better of course but few if any very healthy centenarians will be sporting a 90.

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#10

I think BMI would not qualify as a longevity biomarker. At the peak of his career, for example, Arnold Schwarzenegger’s BMI was 31-32. Moreover, some metabolically healthy people are overweight or even obese, etc.

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#11

homocysteine?
liver panel?
Omega 3 level?
Vit D level?

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#12

Uric acid? (Diet / SGLT2i)

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#13

I don’t think they raise it, I think (from what I remember, I might be wrong) they slow down the pace of decline, no matter where you are. eGFR starts declining in most people between 30 and 40 yo. So if yours has always been the same and above 90: no need? But if it starts declining (even from a high baseline like 110): worth considering? (I don’t know, I’m just thinking “aloud”…)

With dapagliflozin & telmisartan mine whether measured with creatinine and/or cystatine) increased though (from about 100 to about 110). Might not be clinically significant.

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#14

BMI definitely would be a poor longevity biomarker, since it is but a poor proxy of adiposity.
It may be useful together with other anthropomorphic markers such as appendicular muscle mass, waist, hip to waist and so on. I realize something simple is needed, but we know well that significant visceral fat may be present with a low BMI and that, as above explained, those with some muscularity may have a BMI well above 22 with little adiposity.
what comes to my mind is something like IQ-BMI, and individualize qualitative BMI. Everyone with a small knowledge of such measures can do it.

1)Asses visceral fat qualitatively (presence of prominent belly?)
2)Asses muscularity qualitatively (Do I have some degree of hypertrophy or not?)
3)Assess overall adiposity (do I have well-distributed sub-cutaneous adiposity or not?)

On the base of the above simple qualitative considerations, build up thresholds for healthy, longevity-prone BMIs.

Simple example: I have presently a BMI= 22.6 kgm2, no visceral fat, low subcutaneous adiposity, decent although not big muscularity (by bodybuilding standards).
Conclusion: my BMI, even if > 22.0, is well within the optimal range.

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#15

You can press the top right corner to add more biomarkers or edit the original post if anyone wants. No need to wait. If you have a biomarker, drug to decrease it, and the optimal range just add it IMO.

#16

Agree that body composition dexa, not BMI is the way to go. If not able to access, measure thickest bit of your abdomen and if this is >50% of your height you probably have too much visceral and other fat.

Getting visceral fat less than 1.8 lbs is a common goal, and there is some age adjustments, but I think this has to do with normals, not ideals. Men getting body fat <20% and Women <25-27% is a pretty good goal for most. However, you need a DEXA to sort this out accurately.

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#17

With respect to body fat, I would emphasize my comment to keep in mind that the correlation between undifferentiated body fat and metabolic health, healthspan, and longevity is far from perfect. This fact is obscured somewhat by a ubiquitous association unique to advanced societies that consume excess calories of commercialized foods that are highly inflammatory. We are associating fires with the appearance of a fire truck.

While I am not obese or even overweight, two family members and one close mentor friend lived with good healthspan into their advanced 90’s in obese states for the better part of their lives.

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#18

Many have pointed out the limitations of BMI, so let me pretend it is a perfect marker for the sake of discussion for the rest of this reply (even though we know it is not). Just substitute “an accurate measure” for “BMI” in your mind’s eye.

I am on a GLP-1. I would not recommend for people with a BMI of 22. There is a financial cost and an unknown long-term side effect profile to be concerned with here.

The data we have so far suggest that GLP-1’s improve metabolic health systemically. Things typically improved: weight, blood sugar, kidney function, liver (NASH), heart health. Studies are ongoing on all of these.

But if your risk for poor health outcomes based on poor metabolic health is low (in other words, if your metabolic health is generally good), I am not sure we can infer with a high degree of confidence that taking a GLP-1 for an extended period of time will provide a benefit.

There may be some downsides for health that we haven’t detected yet, and if the upside is low (since the person wasn’t particularly ill to begin with) this may not pencil out. Of course it may pencil out; we just don’t know right now with a high degree of confidence.

As well there are other side effects to the drugs, such as gastro-intestinal distress, lower quality sleep, and etc. So quality of life is a bit diminished in my experience. These are not the kind of drug that most don’t even know they are taking.

Regarding ApoB, we’ve had this conversation. I personally take a high dose statin (20 mg Rosuvastatin), Ezetimibe, and low dose aspirin. And I am on a GLP-1, which is helpful as well. My recent LDL was 42 ng/dL, HDL 52, Trigs 66, Total 109. I share this only to establish that I am not anti-cholesterol medicine in a general sense. I am personally taking these drugs.

Why do I take them? My risk factors for ASCVD are so high (based on an atrocious CAC scan result and a family history) that it makes sense to treat to reduce my very high risk. My cardiologists says I should almost consider myself to be in the secondary prevention group when looking at data, instead of the primary prevention group.

Whereas my wife’s risk is, seemingly, very low for ASCVD. Despite her LDL being around 130 ng/dL (I don’t know or track ApoB but I presume these correlate) I don’t think she should manage her cholesterol through medicine at this time. Reducing her cholesterol will reduce her risk of ASCVD; we all know this. But it may slightly increase her risk of something else. Depending on how that math works out, it may or may not be life extending.

What we care about in her case is all cause mortality (ACM). The ACC/AHA risk calculator says her risk is very low - 1.0% on a 10 year basis. We don’t have a lot of data on ACM impact from statin therapy for people whose risk was so low that the guidelines do not recommend the use of statins (to my limited knowledge).

On HbA1c, I am not sure what the target should be, but 5.7 is too high in my opinion. I think somewhat lower is more appropriate, say 5.3. Above that you might want to treat, perhaps with GLP-1’s? I am not sure on this, but I will say that A1c is an extremely important marker.

In any event, as an over all comment, I would say

  1. This is a useful list & thought experiment and I think it is helpful to go down this path.

  2. You can consider adding in some lifestyle elements for those not optimizing those yet - sleep optimization, sun exposure, exercise, and so on. Diet is clearly important but the quality of evidence is pretty poor on exactly what we should eat.

  3. Some more thought could go in to determining risk versus reward for different patients. Medicines tend to reduce risk of the thing they are treating, but tend to have some small risks of making other things worse.

If the risk of the thing being treated is small enough, the small increase in risk from the other things can be greater than the benefit. An example is aspirin in primary prevention, where the benefit in heart disease reduction turned out to be more than offset by the increased risk of bleeds.

In many cases we lack the data needed to make a well-informed risk:reward calculation when we are considering treating people who are at much lower risk than the group that was studied in RCTs was. That is a tricky issue.

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#19

see post #27 for updated list of Attia suggested optimal and recommended ranges now with some sourcing.

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#20

Nice list, other than the ferritin range. The cortisol range was interesting too. Where did you pull this chart from?