Medical Experts Explain Why Biomarkers Offer the Best Roadmap to Optimal Health

Most of us will agree that our health is our most valuable asset in life; however, are we truly living in a state of optimal health and high- level functioning? In other words, are you relying on annual exams and basic bloodwork as a path to longevity and good health? Do you really know your risk factors or the triggers that could fuel future disease? 

“While traditional medicine has been important in the prevention of heart attacks and strokes and lowering blood pressure and blood sugar, the overall preventive aspect of medicine has been very weak,” explains Eric Verdin, MD, CEO and President of the Buck Institute. “We need to stop the idea that you are considered healthy until you are suddenly sick or have a catastrophic event when we know there is gradation. We need to identify who is at risk very early and why. This is why biomarkers are important tools to be employed to allow us to monitor our health.”

Biomarkers measure different aspects of your condition, revealing where you are in your trajectory of health. They can measure the presence or progress of disease, the effects of treatment, and can be good predictors of what the future may hold, so a healthcare provider can intervene aggressively when needed.

“This approach will usher in a different era of medicine which will be much more preventative and more focused on who is at risk,” Verdin said.

We conferred with a group of experts in various areas of health to get the latest cutting-edge information on key markers, important testing, screenings and vital information that you may want to discuss with your own healthcare provider. And as you read on, it will become evident that chronic inflammation is a recurring theme and chief culprit in a variety of health-related issues. 

Cardiovascular Disease + Inflammation

Expert: Mimi Guarneri, MD

Guarneri Integrative Health

Pacific Pearl, La Jolla, CA

“Cardiovascular disease is still the number one cause of death in men and women, but the medical world has been following the wrong markers for many years,” says Dr. Mimi Guarneri, a cardiologist and integrative medicine specialist who co-founded Pacific Pearl in La Jolla, California. According to Guarneri, cardiologists now believe inflammation plays a bigger role in coronary artery disease than cholesterol. Studies have shown high-sensitivity C-reactive protein (hs-CRP) to be more important than low-density lipoprotein (LDL) cholesterol, meaning if two people have the same LDL cholesterol, it’s the one with the higher hs-CPR that does worse with cardiovascular disease. “It’s an inflammatory disease with some very specific markers that everyone should know,” adds Guarneri. In addition to watching your cholesterol levels, it’s imperative to test for inflammation as a preventative and life-saving measure.

Biomarkers

Dr. Guarneri suggests checking the following which can predict cardiovascular disease.

  • Advanced Lipid Panel: checks LDL size and LDL-particle numbers 
  • ApoB: measures potential artery-clogging particles
  • HDL2B: indicates how well excess lipids are removed from cells
  • Oxidized LDL: reveals LDL cholesterol damaged by chemical interactions with free radicals 
  • Hs-CRP: reveals overall inflammation levels in the body
  • Lp-PLA2 + MPO: specifies artery inflammation
  • PULS score: predicts the risk for a cardiovascular event over the next 5 years based on inflammation markers
  • TMAO: high levels of this gut bacteria byproduct formed during digestion can lead to the development of cardiovascular disease, including heart attacks and stroke  

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Guarneri Integrative Health

Dr. Mimi Guarneri, who pioneered the Scripps Center for Integrative Medicine, is the co-founder and medical director of Guarneri Integrative Health at Pacific Pearl in La Jolla, California, where state-of-the-art Western medicine meets the best of holistic and global healing traditions. She is also president of the Academy of Integrative Health and Medicine. Board-certified in cardiology, internal medicine and nuclear cardiology, Dr. Guarneri leads a team of experts in conventional, integrative and natural medicine. 

Cleveland Clinic

This renowned, multi-specialty academic medical center integrates clinical and hospital care with research and education. For 26 consecutive years, the Cleveland Clinic has been ranked as the #1 heart program in the US for heart and vascular disorders, tests, treatments and prevention by the U.S. News & World Report’s “Best Hospitals” list. Stanley Hazen, MD, PhD, the head of Preventive Cardiology, led the team at The Cleveland Clinic to first identified TMAO as a cardiac biomarker in 2018. TMAO is produced when gut bacteria digest choline, lecithin and carnitine — nutrients that are abundant in animal products such as red meat and liver and other animal products. The clinic offers extensive inflammation testing at their Cleveland Heat Lab.

Inflammation in General

“Chronic inflammation is like a smoldering fire,” says Dr. Guarneri. “It can play a significant role in cancer, Alzheimer’s, diabetes, autoimmune diseases, arthritis and more. So if inflammation is driving the train, we have to see where it is coming from.”  

Sources of inflammation range from food sensitivities and gut issues to heavy metals, stress and environmental toxins. Functional testing can reveal how the brain or gut is working and these tests are an addition to traditional bloodwork. 

Biomarkers

For general inflammation investigation, Dr. Guarneri suggests Hs-CRP, Lp-PLA2, MPO, oxidized LDL, and PULS score, the same ones recommended for cardio-related inflammation, along with Homocysteine, TNF alpha + Interleukin 16, which all test for inflammation. In addition, the following biomarker evaluations and tests can help pinpoint the source of your inflammation and give insight to your overall health. But as Guarneri aptly points out, “it’s not only about ordering these tests, it’s knowing how to interpret them, leading to treatment strategies to prevent disease.” 

1. Micronutrient Assessment

A blood and urine test through NutrEval Plasma® evaluates over 125 biomarkers and assesses the body’s functional need for 40 antioxidants, vitamins, minerals, essential fatty acids, amino acids, digestive support and other select nutrients. This test also screens for heavy metals which can cause cardiovascular disease and cognitive decline. “With heart and cognitive disease linked to oxidative stress, it’s important to look at antioxidant and micronutrient levels,” adds Guarneri.

2. Food Sensitivities Assessment

Discovering one’s food sensitivities can be done with bloodwork and through an elimination diet. Culprits include soy, dairy, nuts, eggs, wheat and gluten-containing grains. Food sensitivities cause low-grade chronic inflammation with symptoms like headaches, joint and muscle pain, sinus congestion, IBS, brain fog and more. 

3. Microbiome Assessment

A three-day stool test looks at the cross-section of the bacteria strain living in the gut and inflammation markers (calprotectin and secretory IgA), along with pathogens and parasites. Another important marker in the microbiome to note is Trimethylamine N-oxide (TMAO), as high levels are linked to cardiovascular disease.

4. Adrenal Stress Index

This 24-hour salivary test determines levels of cortisol, a stress hormone that can wreak havoc in the body. If cortisol is too high it can be addressed with nutraceuticals or adaptogens. “Ongoing stress can make you feel fatigued all the time as the body pumps out cortisol to the point where you can’t sleep at night. It’s like being on steroids,” explains Guarneri. The goal is to balance the hormones.

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These two progressive tests deliver insight into your inflammation so you can take action and change the course of your health if need be.

IAge®

The novel Inflammatory Age® test measures one very specific aspect of aging — systemic chronic inflammation, the root cause of major age-related diseases. Based on a 10-year National Institutes of Health (NIH) funded longitudinal research from Stanford University and advanced artificial intelligence methods, a team at Stanford developed the world’s first biomarker composite scoring system to measure inflammatory and immune health of an individual. Inflammatory Age®, founded by Buck faculty member David Furman, PhD, predicts cumulative damage, as measured by the accumulation of up to 10 major diseases of aging including cancer, cardiovascular disease, respiratory, neurologic and gastrointestinal. Based on test results, Edifice Health, a spin-off company to commercialize the comprehensive data collected from the Stanford project, has identified over 150 actionable interventions to improve your Inflammatory Age® including targeted nutritional supplements, immunoactive food ingredients and medical foods. edificehealth.com

Glycan Age

This team in London has created a test for biological age and wellness based on glycans, sugar molecules that cover our proteins and play a role in our health. Bloodwork measures your IgG glycosylation, which directly correlates with the level of inflammation in your body. The testing analyzes 24 glycans — carbohydrate-based polymers that regulate a variety of processes, including immunity — and combines the results to calculate your Glycan Age or biological age. After receiving your Glycan Age you receive a one-to-one consultation with a health specialist who analyzes the results and offers lifestyle interventions if needed. Glycan Age stands out as the first biological age test that has proven responsiveness to lifestyle (and pharma) interventions with statistical significance. glycanage.com

Sleep deprivation causes cortisol levels to go up, blood pressure to rise, weight gain, higher blood sugar, weakened immunity, mood swings and more. In addition to the adrenaline stress index to check cortisol, you may want to be tested for the respiratory disorder obstructive sleep apnea. 

Mayo Clinic

The highly respected Mayo Clinic has sleep disorder campuses in Arizona, Minnesota and Florida. Progressive treatments can be found for narcolepsy, REM disorder, restless leg syndrome, insomnia, sleep apnea and more. 

Bone Health

Expert: Kevin Ellis Integrative Health Coach + Bone Health Advocate

BoneCoach.com

St. Louis, MO

Our bones provide structure, protect our organs, anchor muscles and store calcium. And yet they are constantly changing, as new bone is created and old bone is broken down. Ninety percent of our bone mass is acquired by age 18, and this amount peaks at age 30. From there it’s a decline, gradual for some, while others are not so fortunate. Myriad factors can contribute to bone loss — from age, nutrition deficiencies, hormone levels and gut issues, to stress, poor sleep, medications and other health conditions. Most doctors don’t recommend getting a Dexascan to track bone density until we are in our 50s to 60s, which is often far too late. 

When it comes to testing, Bone Coach Kevin Ellis says, “the earlier the better so you can establish a baseline to monitor.” Anyone with an eating disorder or health issues, or who is postmenopausal, should get a Dexascan as well. Osteopenia occurs when the body doesn’t make new bone as quickly as it reabsorbs old bone, so the bones are weaker than normal. Think of it as a midway point between healthy bones and osteoporosis. Osteoporosis is when the bones becomes weak and brittle with a greater risk for fracture.

If diagnosed with osteopenia or osteoporosis, many doctors will immediately recommend pharmaceuticals like Fossamax or Prolio, but according to Ellis, there’s more biomarker testing to be done and questions to ask before taking drugs that can have severe long-term consequences. Ellis suggests that patients also request a CTX blood test to look at the cells osteoblasts, run bloodwork to check Vitamin D levels, thyroid function and inflammation levels, and a Total Serum IGA test to rule out Celiac disease. “Sixty to seventy percent of people with gluten sensitivity issues may be asymptomatic — unaware that the villi in the small intestines are being damaged and unable to absorb nutrients properly so important minerals are being leached from our bones,” adds Ellis.

Medications can also affect bone health as studies are showing that SSRI’s, PPI’s/proton pump inhibitors, corticosteroids like Prednisone, and breast cancer medications can contribute to bone loss, so discuss the risk versus reward of taking these prescriptive drugs if you have osteoporosis with your healthcare provider.

Biomarkers

UNDERSTANDING T + Z + TBS SCORES

Dexascans provide bone health scores that are important baselines to know. A T-score compares a person’s bone density with that of a healthy 30-year-old of the same sex. The Z-score compares a person’s bone density with that of an average person of the same age and sex.

Normal: A score of -1 or above
Osteopenia: A score between -1.1 and -2.4
Osteoporosis: A score of -2.5 and below

In addition to getting your T-score and Z-score, ask your healthcare provider if their DEXA machine has a Trabecular Bone Score (TBS) capability as this new technology and recently-developed analytical tool can assess the quality of your bone — another important piece to the bone health puzzle. Find a medical group that offers TBS here: medimapsgroup.com/find-a-clinic-with-tbs.

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BoneCoach.com

Kevin Ellis, a certified integrative health coach and bone health advocate, has coached thousands of people with osteopenia and osteoporosis on how to address bone loss, build bone strength, stop fearing fracture, and lead active lives. He and his team of experts offer the latest cutting-edge research, interactive counseling, bone-specific nutrition, hormonal and sleep advice, stress reduction, exercise and physical therapies plans. Their holistic approach is to identify the source of bone loss, nourish the body with minerals and nutrients that are properly absorbed, and build strength through specific exercises that don’t cause injury. bonecoach.com

OSTEOSTRONG

Located across the country, these wellness studios focus on skeletal strength and use a process known as Osteogenic Loading — brief, intensive resistance exercise to stimulate the bone building cells. These sessions can be a great complement to your bone health plan to improve bone density, posture and balance, but anyone with osteoporosis should first check with their healthcare provider to see if osteogenic loading is appropriate for your bone health protocol. osteostrong.com

Genetic Testing

Expert: Eric Verdin, MD, CEO and President


The Buck Institute of Research for Aging + Longevity

Novato, CA

You’ve heard it before: genes are not destiny. Science has shown that the environmental and lifestyle choices like eating well, exercise and sufficient deep sleep play a much greater role than genetic factors  in regard to our health and longevity. “When you look at relative risk in terms of health and life span, the relative roles of your genes versus your environment and lifestyle, the latest number is about 7 percent of the outcomes are from your genes. It’s a really minor component,” explains Buck Institute CEO Eric Verdin. “That said, there is some value in genetic testing.”  

Genetic testing for pregnancy issues and specific forms of cancer can be an effective tool. If you have a history of breast or ovarian cancer, ask your healthcare provider about testing for the BRCA1 and BRAC2 mutations. Testing for Factor V Leiden makes sense when there is a history of miscarriages and blood clots. Even the home test kits like 23andMe look for both of these genetic variants, along with others like the APOe4 mutation, which is predictive for increased risk of Alzheimer’s. Since most people diagnosed with Alzheimer’s disease are already 80 to 90 percent into the process, early detection is key since science is working to uncover potential preventive therapies and treatments.

But one also has to consider the psychological toll of gene sequencing, which can also create a burden of worry and fear. “This is when you have to remind yourself about the relative importance of your genes compared to your lifestyle choices,” says Verdin. “That exercising, eating well, sleeping enough — factors you can control — are so much more important than knowing what your genes are.”

Still Verdin encourages people who are interested in their health to get all the information they can. “But you should have a reasonable expectation of what genomic testing really tells you as it’s somewhat limited. At this point, we do not know to read the human genome very well, but I suspect this will change.”

Biomarkers

Cutting-edge science is providing new ways to understand and measure the factors that cause cognitive decline and accelerate aging. And while there are many biomarkers for a variety of diseases from anxiety to diabetes and cancer, here’s some information on Alzheimer’s Disease and epigenetic clocks.

Alzheimers Disease

Genetic variations in fat-metabolizing Apolipoproteins (APOe) are associated with Alzheimer’s disease and those carrying the APOe4 allele are at increased risk for developing Alzheimer’s disease; the APOe2 variant is protective. Research shows that Alzheimer’s is influenced by many factors including toxin exposure, inflammation, chronic pathogens, vascular compromise, trauma and insulin resistance. While there is much to learn about this disease that affects more than five million people, biomarkers for Alzheimer’s could provide detailed measures of abnormal changes in the brain, inflammation, insulin levels, gut integrity and the blood brain barrier and may help in predicting, monitoring and preventing the progression of the disease.  

Epigenetic Clocks

Geneticist Steve Horvath at the University of California, Los Angeles, a pioneer in epigenetic-clock research, created the Horvath Clock. It measures biomarkers of DNA methylation at 353 different sites in the genome to reveal one’s biological age, which can be either similar or different from your chronological age and correlated to lifespan and health span. Other examples of epigenetic clocks include the PhenoAge Clock by Dr. Morgan Levine at Yale and the GrimAge Clock created by Ake Lu from UCLA

Epigenetics is the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself. It focuses on how your behaviors and environment can cause changes that affect the way your genes work. Biological age is the way in which your cells have changed over time and can be influenced by many different lifestyle factors versus one’s chronological age.

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23andMe

These affordable, director-to-consumer genetic test kits deliver information on ancestry and assess genetic risk for 10 conditions approved by the FDA (Parkinson’s, Celiac, Alzheimer’s and more), though results are not intended to diagnose any health-related issues. DNA is extracted from a saliva sample that’s tested to spot genetic variations as a means to encourage people to be aware of their genetic risks and be more proactive about their health and longevity. Kits start at $199.

Human Longevity Inc. 

American-born biochemist-geneticist J. Craig Venter helped crack the genetic code by sequencing the first human genome and deciphering essentially all the genes in human DNA in hopes of providing keys to the diagnosis and treatment of numerous diseases from diabetes and heart disease to Alzheimer’s and various cancers. He cofounded the company Human Longevity Inc., which offers full genetic assessments to the public with a goal to use this genetic knowledge to transform treatments from reactive to proactive, preventative and personalized. Prices range from $5,500 for basic testing to upwards of $25,000 for full genetic assessment.


Pharmacogenomics

The Way of the Future

Genetic testing has entered the world of pharmacology as pharmacogenomics is the study of how genes affect the body’s response to certain medicines. Before you commit to prescriptives like anti-depressants, statins, or beta blockers, you should consider pharmacogenetics testing to determine how your body metabolizes specific medications to determine which drug works best for your genetic inheritance. This relatively new field will help reduce adverse drug reactions; make better, safer medications; establish more accurate methods of determining appropriate drug dosages; and create better vaccines. 

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Companies like GeneSight, GenoMind, Admera all provide pharmacogenetic testing that makes use of this emerging science, looking at both the effect a drug has on your body (pharmacodynamic parameters) and how your body effects the drug (pharmacokinetic parameters).  

Biomarkers on the Brink…

The Development of Senescence-Associated Biomarkers

The Buck Institute for Research on Aging is studying the SASP (Senescence-Associated Secretory Phenotype), a group of pro-inflammatory molecules that are secreted by cells that are senescent — damaged cells that are no longer capable of dividing. “With age, there is an accumulation of these senescent cells that are spewing off SASP which causes chronic inflammation. We suspect this will be another biomarker — determining the SASP load in the body,” explains Verdin. To that end, the Buck Institute has created a Proteomic Atlas of Senescence-Associated Secretomes, a database of proteins for the research community. The hope is that these biomarkers will help identify factors that drive aging and disease in specific tissues and will lead to early detection and interventions that will prevent disease progression. Those interventions are aimed at eliminating senescent cells in order to decrease the burden of inflammation. Unity Biotechnology, which was incubated at the Buck Institute, is in clinical trials with two drugs which would eliminate senescent cells in diabetic eye disease and osteoarthritis.

Stiffness as a Marker of Age and Inflammation Factor

As we age, our tissues get stiffer which causes tension in our cells. At some point this stiffness can result in fibrosis, which damages our organs. Buck Associate Professor Dan Winer, MD, and his team have discovered that the cellular tension impacts our immune system, creating a negative feedback loop that contributes to the low-grade chronic inflammation that fuels many of the diseases of aging: more inflammation results in more stiffness. Researchers hope to develop new therapies that would blunt the impact of cellular tension on the immune system. Winer says technology that can track stiffness in organs currently exists. That technology could allow for early detection of stiffness and make it easier to test the efficacy of new drugs that would break the inflammatory loop

Best Health Monitors

These devices offer daily information about your personal biomarkers. 

Oura Ring

A favorite of NBA +WNBA players, NASCAR drivers and Prince Harry, this smart wearable is a cutting-edge health tracker that collects data about your body, activity and sleep, measuring body temperature, heart rate, heart rate variability, respiratory rate, REM and deep sleep. It then transmits your results to an accompanying app through Bluetooth and the gives you three daily scores: Sleep, Activity and Readiness, which is the first score you see each morning that reflects your overall health after analyzing your sleep and activities levels. User-friendly and regarded as the best sleep tracker on the market. Guided meditations, too. $299; or $999 for a band with diamonds.

WHOOP

This arm band device delivers daily personalized fitness, sleep and recovery data in real time. While it measures pulse, respiration, heart rate variation and movement, it feels tailored for the exercise obsessed who want to monitor and measure the intensity of their exercise performance, how well they recover and their training capacity for the upcoming day. Whoop uses extensive AI on the server, gives you a questionnaire daily, and then integrates your responses with what it measures to make predictions. Starting at $30 per month.

Apple Watch Series 6

Apple’s latest tech wizardry can measure your blood oxygen level and even take an electrocardiogram with the ECG app to detect irregular heartbeats or signs of atrial fibrillation. Its fitness tracker delivers metrics like heart rate and elevation gain, while its sleep app tracks your shut-eye trends. Not to mention music, workout routines, safety alert features, email delivery, call capacity and more. Starting at $399.

Each of us must be our own advocate for our health. We must get educated and ask questions. Understanding our own biomarkers can enlighten us about the state of our wellbeing, so we can take action that can guide ourselves towards longevity and optimal health.


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Ann Wycoff is a travel and lifestyle writer whose work has appeared in San Diego MagazineCoastal Living, Modern Luxury, and many more. She lives in Encinitas, CA with her husband and daughter, and believes in traveling with a purpose. 

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