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Important Biomarkers for Prolonging Healthspan

The Takeaway:

The following tests are nonstandard in a traditional primary prevention setting yet can provide enormous value for early interventions of chronic, debilitating diseases such as dementia. Genetic testing can stratify the importance of obtaining the following labs through SNPs in genes that code for Lp(a), vitamin D metabolism, methylation, and more.

  • NMR Lipoprofile that includes LDL-P

  • ApoB

  • Lp(a)

  • Hemoglobin A1c

  • Fasting Insulin

  • Vitamin D, 25-OH

  • hs-CRP

  • Serum Vitamin B12

  • Serum Folate

  • Homocysteine

  • Uric Acid

  • CMP

Discussion

There are three questions to consider when ordering a test: 1) Why do you want the test? 2) What are the acceptable values of the test? 3) How is the test going to change management? That is, you want to order a test for a purpose; you want to know how to interpret the test; and you want to be able to act upon what the test tells you. As medicine has advanced, so has the art of preventive care. The labs cited here are exceptionally useful in detecting metabolic derangements that silently increase the risk of diseases such as coronary artery atherosclerosis and dementia. Moreover, an intervention exists for every listed parameter if the lab value is found to be outside of the optimal range.


The nuances of this analysis will be discussed in a future “optimal lab” series where I will explain in depth why I order these labs for myself and the research that supports my choices. I will also present why many of the accepted “normal” lab values today are suboptimal and what the optimal values actually are. For now, please enjoy a brief write-up for each lab.


NMR Lipoprofile

The utility of the NMR Lipoprofile, which is the gold-standard tool to measure LDL-P, has been extensively discussed in a previous post. In brief, knowing your lipid profile and particle count will stratify your cardiovascular disease risk better than a normal lipid panel alone. The NMR Lipoprofile will also give you an insulin resistance score called HOMA-IR, which if elevated, is an indicator that you are at higher risk for developing diabetes. An alternative test to measure LDL-P is an ion mobilization test, however, it does not give an insulin resistance score and is not as accurate as NMR.

ApoB

ApoB100 is a protein that is covalently bound in a 1:1 ratio on lipid particles that have the potential to be atherogenic. Knowing this number, along with an LDL-P, will help stratify risk for atherosclerosis.


Lp(a)

Lp(a) is an LDL particle with an additional protein subunit, named apo(a), covalently bound to apoB by a disulfide bond. The main determinant of Lp(a) levels seem to genetic. It is an atherogenic particle that predicts cardiovascular disease mortality independent of LDL levels.


Hemoglobin A1c

HbA1c is a measurement of the percentage of glycated hemoglobin versus regular hemoglobin at a point in time. This percentage can be extrapolated backwards by the average lifespan of a red blood cell, typically three to four months, to infer the average blood glucose. Interestingly, HbA1c best correlates with mean glucose over the previous two to three months. [10]


Fasting Insulin

Fasting insulin levels will increase as the body compensates for rising insulin resistance even in subjects with normal glucose tolerance. The extra lead time given by measuring both fasting insulin in addition to an oral glucose challenge test allows earlier identification and treatment of insulin resistance with lifestyle modifications.


25-OH Vitamin D

In addition to phosphorus, calcium, and bone health regulation, optimal vitamin D levels can improve glucose regulation, reduce proteinuria, decrease inflammatory markers, and improve endothelial cardiovascular markers, including arterial stiffness. [1,2,3]


Hs-CRP

Hs-CRP is an indication of ongoing inflammation. Higher hs-CRP values have a positive association with metabolic syndrome components and increase the odds of having metabolic syndrome and other diseases. [4,5]


Serum Vitamin B12, Serum Folate, Homocysteine

These labs evaluate the enzymes, coenzymes, and molecules of the methionine and folate cycles. A much larger “optimal lab” series post is in the works for these tests. Elevated homocysteine is a common comorbidity, or frequently occurs with, decreased B12 or Folate. It is also a risk factor for hypercoagulability, cardiovascular and cerebrovascular disease. Improving homocysteine levels into optimal ranges can improve cognitive impairment in elderly and slow the rate of brain atrophy. [6,7]


Uric Acid

Uric acid has been causally linked in large studies with cardiovascular morality. [8] Other studies have confirmed this relationship in women but not men. [9]


CMP

The liver enzyme component of the comprehensive metabolic panel (CMP) can evaluate for intrahepatic pathologies such as non-alcoholic fatty liver disease, which is likely to become the number one cause of liver transplants in the near future.


References:

1 https://www.ncbi.nlm.nih.gov/pubmed/31021286

2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409667/#B83-nutrients-09-00328

3 https://www.ncbi.nlm.nih.gov/pubmed/26432706

4 https://www.ncbi.nlm.nih.gov/pubmed/24716628

5 https://www.ncbi.nlm.nih.gov/pubmed/26115893

6 https://onlinelibrary.wiley.com/doi/full/10.1002/gps.2758

7 https://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-14-6

8 https://www.ncbi.nlm.nih.gov/pubmed/25788527

9 https://www.ncbi.nlm.nih.gov/pubmed/30383640

10 https://www.ncbi.nlm.nih.gov/pubmed?term=17851648

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