Would be great if you could generate a spreadsheet!
I’m doing a deep search in OpenEvidence now. I hope I didn’t break it because it’s been silent for 5 minutes, just spinning and thinking (although this is the first time I’ve done a deep search, so I don’t know what the norm is)
2 Likes
Ok, here we go!
1 Like
I am sharing this link to Matt Kaeberlein’s latest podcast with Dr. Nicki Byrne and Dr. Kevin White. I found it very informative: ‘practical’ approaches to dealing with health and ageing, various conditions and what to track, discussion on a range biomarkers and targets including blood, lipid, genetic, and a lengthy discussion on hormones.
2 Likes
open evidence:
To ensure the biomarker reference ranges are clinically relevant, it would help to clarify the intended patient population and clinical context.
Are you seeking optimal biomarker levels for healthy adults, a specific age group, or patients with particular comorbidities?
Should the reference ranges reflect general population norms, or are you interested in “optimal” levels for disease prevention or longevity?
Are there specific clinical guidelines, geographic regions, or laboratory standards you want the biomarker levels to align with?
You may answer as many of these questions as you like.
I responded:
optimal biomarker levels for healthy adults, I am interested in “optimal” levels for disease prevention or longevity, USA laboratory standards
OpenEvidence responded:
3 Likes
Introduction and Scope
The determination of “optimal” blood biomarker levels for healthy adults in the United States, specifically for disease prevention and longevity, requires a synthesis of evidence from large epidemiological studies, clinical guidelines, and meta-analyses. This report provides a comprehensive, quantitative, and actionable summary of optimal biomarker targets for immune cell counts and function, inflammation, red blood cell (RBC) indices, liver and kidney function, metabolic and endocrine markers, lipid profiles, vitamin and mineral status, and blood pressure. All recommendations are aligned with current US laboratory standards and are contextualized by age, sex, and comorbidities, with explicit attention to the limitations and risks of targeting extreme values.The report also addresses the influence of genetics and lifestyle on biomarker interpretation and monitoring strategies.
Immune, Inflammatory, and Hematologic Biomarkers
Immune Cell Counts and Function
Optimal immune health in adults is best characterized by maintaining lymphocyte subset counts within established reference intervals, with a particular emphasis on the CD4:CD8 ratio and low inflammatory indices. In healthy US adults, the reference ranges for key lymphocyte subsets are as follows: CD3+ T cells, 983–3572 cells/μL; CD4+ T cells, 491–2000 cells/μL; CD8+ T cells, 314–2087 cells/μL; CD19+ B cells, 64–800 cells/μL; and CD16+CD56+ NK cells, 27–693 cells/μL.[1-4] The optimal CD4:CD8 ratio is 1.0–2.5, with values below 1.0 indicating immunodeficiency and values above 2.5 potentially reflecting immunosenescence.[1][5-6] Age-related declines in T and B cell counts and increases in NK cell counts are well documented, and longitudinal trends may be more informative than single measurements.[7][8] Functional immune scoring models that integrate cell counts, cytokine production, and phenotypic markers are emerging but are not yet standardized for clinical use.[9]
Inflammatory Markers
C-reactive protein (CRP) and interleukin-6 (IL-6) are the most robustly validated inflammatory biomarkers for risk stratification in healthy adults. The American Heart Association and Centers for Disease Control and Prevention recommend a CRP target of <1.0 mg/L for the lowest risk category, with 1.0–3.0 mg/L considered average risk and >3.0 mg/L high risk.[10] Longitudinal studies confirm that persistently low CRP (<1.0 mg/L) is associated with reduced risk of frailty, chronic disease, and mortality.[11-13] For IL-6, optimal levels are <1.5 pg/mL, with risk increasing above 2.0–2.5 pg/mL.[13-16]The neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) are also predictive, with optimal NLR in the range of 1.0–2.0 and SII at the lower end of the reference range.[17]
Red Blood Cell Indices
Recent US cohort studies demonstrate that optimal RBC indices for longevity are at the mid-to-upper end of the normal range. The lowest all-cause mortality is observed at a mean corpuscular volume (MCV) of approximately 88.6 fL, mean corpuscular hemoglobin (MCH) of 30.2 pg, and mean corpuscular hemoglobin concentration (MCHC) above 34.3 g/dL.[18] Both low and high values are associated with increased risk, supporting a U-shaped relationship.[19-20] Hemoglobin targets for optimal health are 14.0–15.5 g/dL for men and 13.0–14.5 g/dL for women, within the standard reference intervals.[18-19]
To provide a concise overview of these optimal immune, inflammatory, and hematologic targets, the following table summarizes the evidence-based ranges and their clinical context:
Table 1. Biomarkers of Micronutrient Status.*
Micronutrients — Assessment, Requirements, Deficiencies, and Interventions. N Engl J Med. March 5, 2025.
Used under license from The New England Journal of Medicine.
This table, adapted from a comprehensive review of micronutrient and immune biomarkers, illustrates the reference intervals and optimal targets for key immune and hematologic markers, including vitamin D, B12, folate, zinc, and iodine, which are also relevant to immune function.
Organ Function, Metabolic, and Endocrine Biomarkers
Liver and Kidney Function
For liver function, the American College of Gastroenterology recommends ALT targets of 29–33 IU/L for males and 19–25 IU/L for females, which are lower than many laboratory upper limits and are associated with reduced liver-related mortality.[22] AST, alkaline phosphatase, and bilirubin should be interpreted within standard reference intervals, with values at the lower-to-mid range being most favorable for longevity.[23-24]
Kidney function is optimally assessed using estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR). The optimal eGFR is >90 mL/min/1.73 m² in adults under 40, >75 mL/min/1.73 m² in those aged 40–64, and >60–75 mL/min/1.73 m² in those 65 and older.[25-27]Albuminuria should be <10 mg/g for optimal cardiovascular and renal health.[25]
Metabolic Markers: Glucose, HbA1c, and Insulin
The American Diabetes Association defines the optimal HbA1c for healthy adults as 4.5–5.2%, with the standard reference interval extending to 5.6%.[28] Fasting glucose levels associated with the lowest risk of morbidity and mortality are 70–90 mg/dL (3.9–5.0 mmol/L).[24][28] Lower fasting insulin within the normal range is favorable, but there is no universally accepted reference interval for insulin.[29]
Thyroid and Sex Hormones
A recent meta-analysis of over 130,000 adults found that the lowest risk of cardiovascular disease and mortality is observed with TSH levels in the 1.9–2.9 mIU/L range (60th–80th percentile) and free thyroxine (FT4) in the 13.5–14.8 pmol/L range (1.05–1.15 ng/dL; 20th–40th percentile).[30-31] Age-specific reference intervals are recommended, especially in older adults, to avoid overdiagnosis of subclinical hypothyroidism.[32-35]
For men, optimal total testosterone is above 7.4 nmol/L (213 ng/dL), with both low and very high levels associated with increased mortality.[36-38] In women, there is no clear evidence for an optimal estradiol or testosterone level for disease prevention or longevity.[37-38]
Lipid Profiles
The National Lipid Association and American College of Cardiology recommend an LDL cholesterol (LDL-C) target of <100 mg/dL for healthy adults, with non-HDL cholesterol <130 mg/dL and triglycerides <150 mg/dL.[39-40] HDL cholesterol should be ≥40 mg/dL in men and ≥50 mg/dL in women.[35][40] There is ongoing debate about the benefits of targeting LDL-C below 70 mg/dL in low-risk individuals, but <100 mg/dL remains the consensus target for primary prevention.[41]
The following table provides a summary of optimal ranges for these organ function, metabolic, and endocrine biomarkers:
Table 1. Most Effective Nonpharmacologic Interventions to Lower Blood Pressure
Treatment of Hypertension: A Review. JAMA. November 7, 2022.
Content used under license from the JAMA Network® © American Medical Association
This table, from the American Heart Association, highlights the most effective nonpharmacologic interventions to lower blood pressure, which is a key metabolic and cardiovascular biomarker.
Vitamins, Minerals, and Blood Pressure
Key Vitamins and Minerals
For vitamin D, the Endocrine Society recommends a serum 25(OH)D concentration of ≥30 ng/mL (75 nmol/L), with some evidence supporting 30–40 ng/mL (75–100 nmol/L) as optimal for disease prevention.[21][43-47] Vitamin B12 should be maintained above 300 pmol/L (400 pg/mL) to minimize risk of deficiency and elevated homocysteine.[48-51] RBC folate should be >400 nmol/L (181 ng/mL), with higher levels (>748 nmol/L) recommended for women of reproductive age.[49][52-53] For other vitamins and minerals, such as vitamin A, E, zinc, magnesium, and selenium, the primary goal is to avoid deficiency, with no evidence supporting benefit from levels above sufficiency.[21][50][54-58]
For less commonly measured micronutrients, such as copper, manganese, iodine, and chromium, optimal levels are best defined by established US laboratory reference intervals and deficiency cutoffs.For example, serum copper should be 80–160 μg/dL, serum manganese 4–15 μg/L, urinary iodine 100–199 μg/L (population median), and blood chromium 0.7–28.0 μg/L.[59-69]
Blood Pressure
The American College of Cardiology and American Heart Association recommend a blood pressure target of <130/80 mm Hg for most adults, with consideration of <120 mm Hg systolic in select individuals who can tolerate it without adverse effects.[42][70-71] This target is supported by large randomized trials and meta-analyses demonstrating reduced risk of cardiovascular events and mortality.
Genetics, Lifestyle, and Monitoring Strategies
Genetic and Lifestyle Modifiers
Genetic polymorphisms, including those in APOE, FOXO3A, and antioxidant genes, can influence baseline biomarker levels and their association with longevity.[72-81] However, current clinical guidelines do not recommend genotype-specific reference intervals, and population-based targets remain the standard. Lifestyle factors—such as diet, physical activity, sleep, alcohol consumption, and smoking—have additive and sometimes synergistic effects on achieving and maintaining optimal biomarker levels.[82-91] Adherence to a healthy lifestyle can extend disease-free life expectancy by 8–14 years and is associated with the most favorable biomarker profiles.
Monitoring and Follow-Up
Routine biomarker testing in healthy adults should be individualized based on age, baseline risk, and the specific biomarker. Lipid panels and cardiovascular risk assessments are recommended at least every five years, with more frequent monitoring for those at higher risk.[39-40][92-93] Inflammatory and metabolic markers should be reassessed at intervals of 1–5 years depending on baseline values and risk factors.[10][94-97] Over-testing should be avoided, and repeat testing should be reserved for those with borderline or abnormal results, changes in clinical status, or initiation of therapy.[92-97]
The following table summarizes recommended monitoring intervals for key biomarkers in healthy adults:
Table 3. Summary of Findings by Outcome Domain in a Review of General Health Checks in Adult Primary Care
General Health Checks in Adult Primary Care: A Review. JAMA. June 7, 2021.
Content used under license from the JAMA Network® © American Medical Association
This table, from a review of general health checks in adult primary care, provides a summary of findings by outcome domain, including the impact of routine biomarker monitoring on disease detection and preventive care.
Interpretation, Application, and Limitations
Contextualizing Optimal Targets
Clinicians must interpret and apply optimal biomarker targets within the context of age, sex, and comorbidities. Age- and sex-specific reference intervals are essential for accurate interpretation, as many biomarkers change dynamically across the lifespan and differ between men and women.[98-106]For adults with comorbidities such as hypertension, diabetes, or chronic kidney disease, more stringent targets may be appropriate.[25][42][102-104] Lifestyle modification remains the cornerstone of risk reduction for all adults, regardless of age, sex, or comorbidities.[82-91]
Risks of Targeting Extremes
Targeting biomarker levels at the extreme low or high ends of the reference range is not recommended, as both extremes are often associated with increased risk of morbidity and mortality.[20][105][107-113] Reference intervals are designed to capture the central 95% of values in a healthy population, but are not synonymous with “optimal” or “risk-free” zones. U-shaped or J-shaped associations are common, and the pursuit of extreme values can lead to overdiagnosis, overtreatment, and misclassification, particularly in the absence of individualized context.[20][105][107-113]
Conclusion
In summary, the optimal blood biomarker levels for healthy adults in the United States, for the purposes of disease prevention and longevity, are generally at the favorable end of established reference intervals but not at the extremes. For most biomarkers, maintaining values within these intervals—specifically, CRP <1.0 mg/L, IL-6 <1.5 pg/mL, LDL-C <100 mg/dL, HbA1c 4.5–5.2%, vitamin D 30–40 ng/mL, and blood pressure <130/80 mm Hg—confers the lowest risk of chronic disease and mortality. Age, sex, genetics, and lifestyle must be considered in interpretation and application, and over-testing or targeting extreme values should be avoided. These recommendations are grounded in the most current US guidelines and high-quality evidence, and provide a practical, quantitative framework for clinicians counseling healthy adults on optimal biomarker targets for prevention and longevity.
Table 2. Estimated Number of Disease-Free Life-Years and Age Achieved Disease Free by Level of Healthy Lifestyle Scorea
Association of Healthy Lifestyle With Years Lived Without Major Chronic Diseases.JAMA Intern Med. April 30, 2020.
Content used under license from the JAMA Network® © American Medical Association
This table demonstrates the additive effect of healthy lifestyle factors on disease-free life-years, reinforcing the importance of lifestyle in achieving and maintaining optimal biomarker profiles and extending healthspan.
3 Likes
Here is the spreadsheet of optimal human blood biomarkers with both conventional and SI units, organized by health category. Let me know if you’d like this exported as an Excel or CSV file, or customized for a specific age, sex, or condition.
Optimal_Blood_Biomarkers_with_SI_Units.xlsx (13.3 KB)
4 Likes
I would like to customize it to my age (70 yo female), and condition “post kidney transplant”, Excel file would be OK. Thanks a lot.
1 Like
To add to what @LaraPo said … but it would be great to have something ‘relativized’ to various age groups - e.g. over 60, over 70, etc, if that is possible.
2 Likes
I can put in the request, but I am not sure it would be to that well done
C’mon John. You made the offer. No backing out!
(Pretty sure he copy/pasted the end of the chatgpt response, where it just continues to offer ways to maintain engagement. And rapanewsies are like ‘Why yes, I’d like mine cooked at 350F for 20 minutes, on whole wheat, hold the mayo.’)
I need to be at my laptop to do this. Which I am willing to do, but I make the point that the variation should be validated.
Oh it’s totally OK not to customize it for me. I don’t want to take @John_Hemming time, he already provided valuable info. Thank you @John_Hemming for doing that.
It’s not a time issue. I was at a jazz festival yesterday and won’t be on my laptop for a few hours now. I also need to remember to do this.
1 Like
I have asked a few more questions and here is the link
I don’t mind asking 10 more questions relating to this. I have not looked at the answers myself and I am concerned that the more detailed a question tends to be often the less reliable LLM answers are.
Hence if people want me to put in up to 10 more questions and update the share I will do this.
1 Like