OK. What Next? (Biomarker Targeting)

So, I’ve gotten my blood glucose at a level I want 4.9 HBA1C) and cholesterol where I want (66 LDL) and BP in range (106-115).

So what do we shoot for next? Which biomarker is the most important after the big three above? Thoughts on what the next 3 most important biomarkers are we should shoot for?

Provide a list and reasons:

  1. X because…
  2. Y because…
  3. Z because…

Do you think it’s Metformin that brought your HA1c to 4.9? Mine is 5.7 and I’m struggling to lower it.

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A lot depends upon what your other biomarkers are.

If there is one or a group that is out of kilter then those logically would be the priority.

Similarly if you have functional issues that need fixing then that is a priority.

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Akkermansia brought my HbA1c down to 5.0 from 5.5 (5.8 at one point).

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This is a really good question. Broadly speaking there seems to be a hierarchy of biomarkers that are likely key for longevity given what we know about reasons most people die (and of course adjusted for your own personal risk factors).

  • Blood glucose levels are one obvious one
  • Cholesterol / APOB, LP(a)
  • Blood Pressure

I think an important biomarker is a VO2Max of somewhere over 35 ml/kg/min for people over 50, and perhaps over 40 ml/kg/min for people over age 40 (and the higher the better).

More Here: Exercise, VO2 max, and longevity | Mike Joyner, M.D

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There are some attributes I’d work on that don’t have biomarkers. Muscle mass, fast twitch muscles, balance, reaction time. All working toward fall prevention, and general health.

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I am tracking:

Hours of sleep every night (circadian rhythm alignment, stress mgmt, etc)

BP / pulse pressure (NO, artery stiffness)

HbA1c (metabolic / mitochondrial health with a balanced diet)

RHR (heart “strength”, recovery status)

Hang time from a bar (or weight in suitcase carry)

Days of sunshine (see sunrise outside, 10 minutes of midday UV)

Body fatness (Dexa) — soon

Minutes with spo2 <90% (shallow breathing)

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Actually, I forgot that I did a one month stint with Pendulum Akkermansia and Polyphenols a couple of months ago. That may have been part of the key. Akkermansia loves Metformin too, so it could have been a synergistic pairing that dropped my HBA1C from 5.7 to 4.9.

My HBA1C was 4.9 back in 2019 when I was taking 2 g of Metformin daily, so it really may be the Akkermansia doing it. I’m only taking 500 mg of Metformin daily now.

Also back in 2019, my LDL was 66, just as it is now. Seems that Bempedoic Acid brought me back to my youthful levels of lipids and nullified the negative effects of Rapamycin on lipids for me.

My new Levine age is 11 years younger than my chronological age. I’ll take that.

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Are you following 1 rep max, or total volume (time). How are training to increase?

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Bar hang — I hang for as long as I can once per workout 3X/wk. I don’t kill myself but I wait until I’m straining. I track time per hang.

Suitcase carry - I walk around an indoor track. I haven’t measured the distance or the time. I carry the weight that I can only just make it around the track. Since it’s a one handed carry i can switch hands if i need a rest while I progress upward in weight. Once per workout 3X/wk. I track max weight.

These two are harder to do in the same workout so I’ll alternate on which one I am emphasizing on a particular day. I’ll go easier on one of them each workout.

These are exercises that I particularly dread. It’s a good sign that I need it.

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Any exercise is good as we all know but I want to push back a bit in the Attia outlook of trying to “pass a test” by hanging or carrying kettlebells or whatever.

I think we should remember that one gets good at whatever one trains for. So thinking you have ensured longevity by hanging from a bar is a little dumb. It ignores the “weakest link in the chain”. When you spend time optimizing one modality you are doing it at the expense of another.

The approach I prefer is to realize you need to do everything (vs great grip strength and no balance - by example). With that outlook find the activities and mix of movements that you enjoy that give you the broadest set of functional capabilities.

Next time you’re somewhere with lots of exercising people look at the young athletic ones. Look at how they move vs you. Are you as fluid? As strong? As flexible? As explosive? Have that kind of endurance? That should give you the factors you need to work on. If you’re pretty strong but inflexible reallocate some time to balance that.

You dont need to match a much younger person but do become aware that you need functionality in all domains.

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These a great improvements. How has the blood pressure changed?

Can you share your bloodwork more broadly?

What are your inflammation levels, for instance last couple of hs-CRPs? Same for IGF-1 levels?

What do your glucose patterns after meals look like? Do you have CGM data.

Insulin levels and homa-IR?

Is your liver and kidney function - that is extra important when one take a lot of supplements and medicines.

Agree with VO2 max. Also knowing your zone 2 and then comparing how that changes over time.

Dexa or mri to understand body composition

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Have also found it helpful to subjectively feel how I’m doing stress, mindfulness, etc wise and subjective sense of sleep quality

  • also following measures trends in
    (i) resting heart rate
    (ii) HRV
    (iii) over night respiratory rate

(very easy via eg Whoop or Oura, although at this point while good for trends, would not rely on any one metric.

I record my fitbit HRV and also the Polar/Elite HRV. I find sometimes that when I am drunk that increases the fitbit HRV (compared to sober) which to me makes me think it is not that reliable. Alternatively it might be that actually when asleep and drunk the HRV goes up, but it goes down compared to sober when I wake up.

I’d love to know how you got your BP down to that level.

In response to your original question, “What’s next”

Inflammation. C Reactive Protein

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Agree that it’s the weak link that gets you. A hang or grip workout is not a gimmick if a strong grip would keep a person from falling (holding onto a railing). The hang workout is supposed to keep the should joint healthy which keeps the door open to all sorts of fun activities (with lots of health benefits to be had), and also helps with that hold-on-to-railing thing.

A strong grip and strong shoulders have saved my life (possibly) many times already.

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I was just watching this video by Mike Lustgarten and he mentions he’s developed his own list of “Optimal” Blood Biomarkers that he’s targeting…

@Davin8r could you check on OpenEvidence to see what you can find in terms of what the optimal levels are for these biomarkers (vs. just average or acceptable ranges).

I’m using this prompt when I search on the standard LLMs:

“What are the optimal human blood biomarkers level for the variables are are commonly checked for areas like immune cells and function, inflammation, RBC measures, liver function, kidney health, hormone levels, metabolic health, thyroid function, lipid levels, vitamin levels, and blood pressure?”

@John_Hemming could you please try this search on the pay version of ChatGPT?

Here is my version of the response from the free ChatGPT:

and below in a PDF document (for some reason it isn’t the complete response provided above, see the link above for the full details):

Optimal_Blood_Biomarkers_with_Notes.pdf (2.6 KB)

Here is the Grok, X.ai response:

https://grok.com/share/bGVnYWN5_64c8f773-4ec1-493a-8f51-6195682409b1

Here is the Claud.AI response to that prompt:

https://claude.ai/share/0e917ec9-bc05-46de-aee6-4babfa20adf0

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Here is a comprehensive table of optimal (not just normal) human blood biomarker ranges for healthspan/longevity, organized by category: immune, inflammation, RBCs, liver, kidney, hormones, metabolism, thyroid, lipids, vitamins, and blood pressure. These values reflect evidence-based, functional medicine-informed targets rather than conventional reference ranges, which often include unhealthy populations.


:test_tube: IMMUNE CELLS & FUNCTION

Marker Optimal Range Notes

WBC Count 4.0 – 6.0 x10⁹/L Low-normal better; high may indicate inflammation
Neutrophils 40 – 60% Balance with lymphocytes is key
Lymphocytes 30 – 50% Crucial for adaptive immunity
Neutrophil-to-Lymphocyte Ratio (NLR) 1.0 – 2.0 Higher values linked to chronic inflammation and mortality
Monocytes 4 – 8% Elevated in chronic infection, inflammation
Eosinophils <3% Elevated in allergy or parasitic infection
Basophils <1% Rarely elevated unless allergic/inflammatory disease


:fire: INFLAMMATION MARKERS

Marker Optimal Range Notes

hs-CRP <0.5 mg/L <1.0 is low risk, <0.5 optimal
IL-6 <1.0 pg/mL Lower is better; high linked to frailty
TNF-alpha <2.5 pg/mL Lower is better
ESR <10 mm/hr Nonspecific, but elevated in chronic inflammation
Fibrinogen 200 – 300 mg/dL Higher levels = clotting/inflammation risk


:drop_of_blood: RBC & OXYGEN CARRYING CAPACITY

Marker Optimal Range Notes

Hemoglobin (M/F) 13.5–15.5 / 12.5–14.5 g/dL Too high or low is problematic
Hematocrit 40 – 47% Higher increases viscosity risk
RBC Count 4.5 – 5.3 x10¹²/L Elevated in dehydration or hypoxia
MCV 85 – 92 fL Micro/macrocytosis outside range
RDW <13% Higher values linked to mortality
Ferritin 50 – 100 ng/mL Optimal balance; >150 = inflammation/oxidative risk


:dna: LIVER FUNCTION

Marker Optimal Range Notes

ALT <25 U/L Lower values linked to longevity
AST <25 U/L AST:ALT ratio >1 may indicate mitochondrial damage
GGT <20 U/L Sensitive marker for oxidative stress
ALP 40 – 80 U/L Higher in bile duct disease
Bilirubin (total) <1.0 mg/dL Mild elevation may be protective (e.g., Gilbert’s)


:petri_dish: KIDNEY FUNCTION

Marker Optimal Range Notes

Creatinine M: 0.8–1.1 / F: 0.6–0.9 mg/dL Muscle mass dependent
eGFR >90 mL/min/1.73 m² >60 acceptable; >90 optimal
BUN 10 – 16 mg/dL High may indicate catabolism or kidney issues
BUN:Creatinine Ratio 10 – 16 Higher suggests dehydration
Uric Acid 4 – 5.5 mg/dL >6 = increased metabolic/CVD risk
Cystatin C <1.0 mg/L More accurate renal marker than creatinine


:brain: HORMONES (MIXED SEXES; ADJUST FOR AGE/SEX)

Marker Optimal Range Notes

Testosterone (free) M: 15–25 ng/dL / F: 1.0–2.5 ng/dL Decline with age; free T more relevant than total
Estradiol (E2) M: 15–35 pg/mL / F: cyclic (20–250) Low E2 = bone/cardiovascular risk
DHEA-S Age-adjusted: 200–400 μg/dL in 30s Falls with age; longevity-linked
IGF-1 100–200 ng/mL Lower end may favor longevity
SHBG 30 – 60 nmol/L High = low free sex hormones
Progesterone F: 1–10 ng/mL (luteal); M: 0.1–0.3 Balances estrogen effects


:gear: METABOLIC HEALTH

Marker Optimal Range Notes

Fasting Glucose 70 – 85 mg/dL <90 is low risk; >100 is prediabetic
HbA1c 4.8 – 5.2% <5.0% ideal for longevity
Fasting Insulin 2 – 5 μIU/mL Higher values = insulin resistance
HOMA-IR <1.0 Calculated from glucose and insulin
Lactate 0.5 – 1.5 mmol/L Elevated = mitochondrial dysfunction
Ketones (fasted) 0.3 – 0.7 mmol/L Mild ketosis may benefit metabolism


:butterfly: THYROID FUNCTION

Marker Optimal Range Notes

TSH 0.5 – 2.0 mIU/L >2.5 suggests early hypothyroidism
Free T4 1.1 – 1.6 ng/dL Low with high TSH = hypothyroid
Free T3 3.2 – 4.2 pg/mL Higher normal correlates with energy/metabolism
Reverse T3 <15 ng/dL High = stress or metabolic slowdown
TPO antibodies Undetectable Autoimmune marker


:syringe: LIPIDS & CARDIOVASCULAR MARKERS

Marker Optimal Range Notes

LDL-C (direct) <80 mg/dL ApoB better marker for atherogenicity
ApoB <65 mg/dL Better than LDL for CVD risk
HDL-C >60 mg/dL Higher = protective
Triglycerides <70 mg/dL Lower is better for metabolic health
TG/HDL Ratio <1.0 Best lipid predictor of insulin resistance
Lp(a) <30 mg/dL Genetically driven; hard to lower
hs-CRP <0.5 mg/L Covered above; also CVD relevant


:tangerine: VITAMINS & MICRONUTRIENTS

Marker Optimal Range Notes

Vitamin D (25(OH)D) 40 – 60 ng/mL >60 offers no benefit; <30 is deficient
B12 500 – 900 pg/mL Methylmalonic acid more specific
Folate >10 ng/mL Needed for methylation, RBCs
Homocysteine 5 – 8 μmol/L Elevated in B-vitamin deficiency, CVD risk
Magnesium (RBC) 5.0 – 6.5 mg/dL RBC magnesium better than serum
Zinc 90 – 120 μg/dL Balance with copper matters
Copper 70 – 110 μg/dL Copper:zinc ratio ~0.8–1.0 optimal


:arrow_down_small: BLOOD PRESSURE

Marker Optimal Range Notes

Systolic BP 100 – 120 mmHg <130 still acceptable
Diastolic BP 65 – 80 mmHg <60 may impair perfusion
Pulse Pressure 30 – 50 mmHg Higher = arterial stiffness


If you’d like, I can generate a printable or spreadsheet version of this for ongoing tracking, or create a personalized version based on your lab results.

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My response from OpenEvidence.com (I’m not a registered user):

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