Science 101

Why Biomarkers Are the Measurements of Modern Medicine

Everything from your heart rate to your blood pressure are trackable — and they can change over time. The best part? You have control over them.

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Everytime you step on a scale, you’re logging a biomarker. And every second your smartwatch logs your heart rate, it’s recording a biomarker. Every doctor’s visit, that blood pressure and body temperature that are taken — both biomarkers. The word isn’t exactly colloquial, but ask any doctor, nurse, researcher, or scientist and they’ll be well acquainted with the term. Rodolphe Barrangou, the Todd R. Klaenhammer Distinguished Professor in Probiotics Research at North Carolina State University, who uses biomarkers every day in his research, defined them as “health indicators that we can measure and quantify and compare to a range that is desirable or healthy in a general population.” Simply put, they’re measurements — biological markers (“biomarkers”) that are objective, quantifiable, accurate and repeatable.

Since 1998, biomarkers have been defined by the National Institutes of Health Biomarkers Definitions Working Group as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” Those three categories — biological, pathogenic and pharmacologic — cover the primary uses of biomarkers. 

Biological includes monitoring the normal processes of aging through our standard health checks. Think of your annual physical at the doctor, covering blood pressure, body temperature, weight and heart rate. Pathogenic biomarkers help establish signposts for chronic diseases and are more specific to a particular case. If a patient is diagnosed with glaucoma, a standard biomarker check would be eye pressure. Or if a patient has a high rate of glucose in their blood — a glycated hemoglobin (A1C) test comes in high — they may be pre-diabetic or diabetic. And pharmacologic biomarkers can help identify the effectiveness of a treatment. For that same glaucoma patient, the optometrist can use the eye pressure biomarker to check the effectiveness of a new eye drop, or the diabetic patient can take a pinprick test to regularly check their blood sugar levels.

Biomarkers are a subset of medical signs — different from medical symptoms, which are patient described. Medical signs are observations by a professional about a patient, and they’re significantly more objective than self-described symptoms. Biomarkers take that a step further, being more accurate, reproducible, and more quantifiable than the broader medical signs. A patient may describe their heart as “racing” and a doctor may notice the patient is agitated, but the best measurement is to take their heart rate — an objective, quantifiable biomarker.

To know if a biomarker is normal or abnormal, it is compared against an existing standard for that measurement. 

“There are predetermined sets of biomarkers that enable investigators to measure an intervention regiment — like a drug or a dietary supplement — and see the impact of a measurable biomarker,” Barrangou says. If your resting heart rate is 130 bpm, the doctor or nurse can know something is amiss, because a normal range is between 60 and 100 bpm. Or, if your body temperature is above 98.7 degrees Fahrenheit, it may signify that your body is fighting an infection.

“Some biomarkers are unequivocal,” Barrangou says. “There’s no questioning the correlation, how you measure it, what it is.” Examples he provides are DNA tests or red and white blood cell count. Other biomarkers, like the signs of irritable bowel syndrome (IBS) can be much harder to define. And some are easy to measure, but harder to interpret. BMI can be measured easily but must be interpreted correctly. An athlete with a high percentage of muscle mass is going to reflect a higher BMI — but this doesn’t mean they are more at risk of conventional diseases associated with high BMI, like diabetes. Body temperature is also easy to measure and interpret but is less specific. It is a very good biomarker for infection, doesn’t tell you which infection is ailing the patient. The doctor may need to determine additional biomarkers — or combine biomarkers with medical symptoms — to make a diagnosis.

Biomarkers for Health and Aging

There are quintessential biomarkers for checking health and aging, as well as many tailored biomarkers for each patient’s unique medical and family history. For general monitoring, two primary metrics are weight and BMI. As a recent review of research reinforced, there’s an established inverse relationship between BMI and lifespan, though some numbers need interpretation, as the report notes that BMI’s “limitations are well known.” Another valuable biomarker is resting heart rate and exhaustion heart rate, the latter being commonly calculated by subtracting your age from 220 bpm. Barrangou notes these biomarkers are excellent indicators of overall fitness and heart health, though you need to take into account individual variability. This is why tracking your own biomarkers over time is so critical, since deviations from previous patterns are noteworthy.

Blood pressure and cholesterol are other good biomarkers for heart health. Both of these biomarkers are commonly checked during an annual physical, and for good reason. High blood pressure increases the risk of stroke and cardiac arrest, and high cholesterol values are good risk indicators for coronary and vascular disease. Anecdotal observations on urine can also be a good check to see if a more conclusive test is necessary. Urine reflects the nutrients in your diet — and a diverse, nutrient-rich diet is good for long-term health. If your urine is consistently an off color (other than yellow or clear) or smells distinctly odd, it may be time to check with a doctor.

Your fingernails and toenails can also be a good marker for cell health. Barrangou notes that nails that grow in evenly, quickly and firmly are a good sign of cellular health. Other ad hoc biological checks include stress levels, sleep habits and fitness levels — the conventional markers of health. 

“If you sleep and you’re lean and athletic and you have a good heart and low blood pressure and low stress and no history of diseases in your family, then we’re just cross-checking that everything looks good,” Barrangou says. While these aren’t objective biomarkers, they’re a helpful way to monitoring to see if more informative biomarker checks are warranted. 

Biomarkers get more specific when checking certain health conditions and chronic diseases. For cancer, biomarkers are an important part of identifying early stage cancers (diagnostic), forecasting how aggressive a condition is (prognostic) and predicting how well a patient will respond to treatment (predictive). Ideally, this is done from a non-invasively collected biofluid (like blood). And, to identify which traits are normal or abnormal, researchers are working quickly to both identify and validate cancer biomarkers — although this work is still developing. The Early Detection Research Network (EDRN) works with over 300 investigators from 40 private or academic institutions to not only establish biomarkers, but also to streamline the process of applying a biomarker to clinical applications. For clinical purposes, a biomarker must be validated by different institutions and in many samples before being approved by the FDA. One large step forward for this validation was when the five phases of biomarker screening development were established in 2001, which helped create universal processes and standards to accelerate the process from lab to clinic, which can also accelerate treatment options.

Biomarkers are especially helpful in cancer research as surrogate endpoints. Clinical endpoints are a final “yes” or “no” condition of a disease; as Barrangou notes, “Is your condition better or not? Is the disease still present, or is it cured?” While clinical endpoints are conclusive, they take much longer to establish, since the final result may take years to occur. Surrogate endpoints allow researchers to make conclusions about the effectiveness of a treatment by monitoring biomarkers and greatly accelerating the result.

“Information can be obtained earlier, more quickly, and more cheaply,” one report stated succinctly. And this involves assessing treatments that are both working and those that are not — cutting down on “wasted” time chasing down a treatment that isn’t performing. Although the speed at which surrogate endpoints allow the research process to occur is great for rapid progress, the accuracy, when compared to clinical endpoints, is not as precise, so the process for using a biomarker as a surrogate endpoint must be taken with extreme scrutiny. And this pithy phrase is especially apt: “all surrogate endpoints are biomarkers, not all biomarkers are useful surrogate endpoints.”

Biomarkers are also becoming more advanced when it comes to understanding disease and aging as new technology and research methods emerge. For example, DNA methylation, a type of epigenetic modification, has been shown in studies to be an accurate predictor of both healthspan and lifespan, such that researchers can establish a “phenotypic” or “biological” age for a person that is more representative of health than chronological age. In the future, this could be used to predict health issues and even as a diagnostic, but more research will be required to understand exactly how to implement it.

What to Know About Your Biomarkers

For those looking to keep tabs on their own biomarkers, the first step is to learn and document your family’s health history and your own health history. Just as important as checking basics like BMI, heart rate, blood pressure, cholesterol, and urine is knowing your own health story. Hereditary diseases and predispositions are a major consideration for biomarker checks, and the more you know the better you can check for normal or abnormal signs. For example, if your family has a history of colorectal cancer, it’s encouraged to begin screening before the normally recommended age of 45. Or if someone in your family fought breast cancer, one can check if she has a mutation of BRCA1 or BRCA2 genes — a reliable biomarker to know if there’s an increased risk of breast cancer.

It’s also important to note that behaviors can greatly impact your predispositions. There’s a reason the nurse or doctor asks you about your current habits and history with smoking, drinking, or drugs (recreational, illicit, or prescription). Behaviors can make you more likely to contract certain chronic diseases and you should be tracking specific medical signs and biomarkers to stay aware of your health. Lifestyle, diet and environmental factors play a major role in the prevention — or development — of chronic diseases.

To best track your biomarkers, know your family history, know your predispositions and know your red flags. Armed with that knowledge, you can track and test your own biomarkers — things like BMI, heart rate and blood pressure are easy to check at home. Wearable devices can be very useful for tracking your biomarkers. More specific treatments, like the pinprick test for blood sugar levels, may be prescribed for specific conditions. Talk to your doctor about concerns based on your family and health history and current habits, and consult with them on the recommended biomarkers to track. And, when exploring treatments for conditions, you can speak to your doctor to learn what the biomarkers of progress are to ensure the treatment is working. Biomarkers are the building blocks for understanding our health. Objectivity, quantifiability, accuracy, and repeatability are vital — and by following key biomarkers you can reliably track your health history, helping to identify health risks and track your progress toward long-term health.

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