April 16, 2019
When it comes to testing your blood, I’m a fan of paying the closest attention to the biomarkers that have been proven to be associated with the aging process.
After all, if you can control for these blood values, you can be relatively confident that you’re going to maintain not just a reduced rate of biological aging, but also superior overall health.
In today's article, you'll learn the 11 best biomarkers to track for longevity as well as what you should do if your values are high or low. Please realize that (as you'll shortly discover in detail) lab reference ranges are flawed and very non-specific to your physical activity levels and exercise goals, your current diet, your health history, and many other factors. I am not a doctor and this is not to be taken, interpreted or construed as medical advice. Please talk with a licensed medical professional about this. These are just my own personal thoughts and not a prescription or a diagnosis or any form of health care whatsoever.
And sure, there are many, many other parameters you could track in addition to what you'll find in this article, but these particular markers are those I've chosen specifically for tracking your longevity. As usual, leave any questions, comments or feedback below the post, and stay tuned for a podcast soon during which I'll detail all of this via audio too! You can subscribe to my podcast for free here.
When Normal Ain’t Normal
Before we jump into the exact biomarkers I recommend that you track, there's one very important caveat: when a doctor or physician performs a test like a blood or saliva panel to look for health-related biomarkers, he or she compares your personal results to the results of the average population, which is known as a reference range or reference interval. This allows a physician to see how your test results compare to what’s considered normal. About 80% of doctors’ recommendations, diagnoses, and prescriptions are based on lab tests and their reference ranges.
But reference ranges may not be as normal as they are supposed to be. In this context, “normal” doesn’t necessarily mean “ordinary” or even “optimal.” “Normal” refers to how the values from an average population create a range or distribution of numbers on a graph.
When values are placed on a graph, the average value lies in the middle, and half the population’s values lie on the left side of the average (the lower half of the range) while the other half’s lie on the right (the higher side of the range). These values account for 95% of the population. Once 95% of the population is accounted for in a reference range, any remaining values are considered to be the tails of the curve on a graph, resulting in about 2.5% of the measured population falling outside of the reference range on either side.
Here’s the first reason why reference ranges can be problematic: there’s no universal range for most lab tests.
Thus, different labs will have different ranges, so if you go to one lab for, say, a blood test, you might get normal results that suggest you’re perfectly healthy, but if you get the same test at a different lab, you might get abnormal results. Most labs don’t even carry out their own research to establish reference ranges but instead use those provided by test manufacturers.
In addition, when using these provided ranges, labs are supposed to perform 20 sample tests to verify that the manufacturers’ ranges are accurate, but most labs don’t even perform this step!
Granted, reference ranges can be useful since they give fixed values for biomarkers from relatively healthy populations, which gives healthcare providers a way to analyze your personal results, diagnose conditions, and prescribe treatments. Ranges also give you (the patient) a chance to see how your biomarkers measure up to those of tested populations.
But ranges don’t account for large population research, which often suggests completely different ranges for diagnosing disease and mortality risks. Reference ranges also don’t account for genetic individuality and differences in environment but instead act as a blanket, one-size-fits-all approach for diagnosing. The ranges are based on “healthy” populations, but these can be hard to define or find since a reference population may include people with undiagnosed diseases or conditions that affect their results for a given lab test.
And, as mentioned above, just because a certain range of values is considered to be normal doesn’t mean that those values are optimal – it just means those are the average values of the population that was tested.
The second reason why laboratory reference ranges need to be viewed with a wary eye is that they don’t necessarily reflect levels that would help you go from good to great but simply the levels that allow for the absence of disease.
For example, thyroid stimulating hormone (TSH) is often not flagged as high until it reaches levels above 4.0, but many people – although they may not have full-blown hypothyroidism – can still feel sluggish or show signs of low metabolism or low thyroid activity with levels as low as 2.0.
The same can be said for testosterone. The low levels set by reference ranges you see on a lab test are often set so low that they just show a red flag if you have hypogonadism, but they aren’t necessarily set at levels that would allow for high libido, fast exercise recovery or increased physical performance. In these two scenarios, you may finish looking at your test and think your thyroid and testosterone are just fine when, in fact, they should actually be addressed if your goal is peak performance.
Another reason why reference ranges frequently don’t represent optimal ranges is that they are often applied to both men and women when, instead, men and women should ideally have separate ranges for many markers.
For example, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are liver enzymes that are used to measure liver function, liver damage, and non-alcoholic fatty liver disease. One reference range allows for AST to vary from 10 to 40 U/L (units per liter) and ALT to vary from 7 to 56 U/L for both men and women. But research indicates that while this may be a “normal” range, it’s far from ideal for either men or women. Several research reports on liver enzymes suggest that for men, ALT shouldn’t exceed 30 U/L, and for women, it shouldn’t exceed 19 U/L. One study performed to determine upper cut-off values for AST and ALT states that in men, ALT shouldn’t exceed 22.15 U/L and AST shouldn’t exceed 25.35 U/L, while in women, ALT shouldn’t exceed 22.40 and AST shouldn’t exceed 24.25. Dr. Bryan Walsh, a board-certified naturopathic physician and the man behind the Walsh Detox protocol, claims that ALT and AST shouldn’t be much higher than 20 and that their reference ranges in men and women should be different.
While the exact mechanism behind different ideal ranges for AST and ALT is largely unknown, another study suggests that hemoglobin may be responsible. High hemoglobin levels have been shown to be strongly associated with elevated ALT levels in men, and hemoglobin is typically lost through bleeding. Since men don’t have a monthly menstrual cycle by which they lose regular amounts of blood, they typically have higher hemoglobin levels than women, possibly resulting in higher levels of liver enzymes.
So if you order a blood test, and your results fall outside of the “normal” range, that doesn’t necessarily mean you’re sick or have a higher risk of getting sick. After all, reference ranges come with built-in bumpers on either side to allow for 5% of the population to have out-of-range biomarker values, and 5% can be an enormous number of people, including you.
The 11 Best Biomarkers To Track For Longevity
OK, let's jump in. If you care at all about how well you’re doing in the longevity game, you’re curious how fast you’re aging, or you want to quantify the efficacy of your healthy eating and healthy living efforts, it’s worth paying attention to each of the following parameters.
The following list is by no means comprehensive but includes those that I consider to be the most important biomarkers to track.
1. RBC Magnesium
Accurately measuring magnesium levels can be difficult. Magnesium is found primarily within your cells (intracellular), so most blood tests for magnesium do not detect a significant deficiency because they measure what is outside the cells (extracellular).
Despite this fact, most physicians measure magnesium with a simple blood test, and many people are then informed that their levels are normal. But to get an accurate reading, you need to measure intracellular magnesium levels, which can be done by testing red blood cells.
Red blood cell (RBC) magnesium measurements can help predict important longevity markers such as insulin sensitivity and likelihood to be hospitalized. High levels of RBC magnesium can predict physical performance and potential for sarcopenia (muscle deterioration) as you age.
As mentioned above, an RBC magnesium test can provide an earlier indication of magnesium deficiency than a standard magnesium blood test. This is because when levels are low, the body will pull magnesium from the red blood cells to keep blood levels normal. In this case, a magnesium blood test may show normal levels while an RBC magnesium test will give a far more accurate result. The ideal range for RBC magnesium levels is 6.0 to 6.5 mg/dl (the normal reference range is 4.2 to 6.8 mg/dl).
While you can request an RBC magnesium test via a blood test during a visit to your doctor or healthcare provider, you can also order one yourself through an independent lab, such as DirectLabs, or get the test as part of the comprehensive blood panels I designed for men and women that are available through WellnessFX, which both include RBC magnesium measurements.
Finally, as an alternative to RBC magnesium testing, some physicians will test magnesium by scraping some cells from the tongue and smearing them onto a slide that is sent to a lab that can analyze the contents for magnesium. A lab called Intracellular Diagnostics offers this test, and it is just as accurate as an RBC magnesium test.
While you’ll learn about full hormone panels later in this article, some of the most important hormones to test for in both men and women are estrogens, particularly estradiol, the major female sex hormone.
Estrogens aid in regulating bone mass and strength by stimulating bone-forming osteoblasts and inhibiting bone-absorbing osteoclasts. This type of bone support is crucial for reducing age-related fractures and even maintaining healthy production of new blood cells as you age.
Bones also provide endocrine support since they are involved in maintaining calcium levels. Interestingly, when women are treated with exogenous estrogens, reductions in bone mass and increases in bone turnover can be reversed, suggesting that estrogens have a potent bone-protective effect.
Estrogens also protect against oxidative stress and participate in the antioxidant system by decreasing the expression of NADPH oxidase, an important source of superoxide radical and increasing the availability of nitric oxide, an antioxidant naturally produced in the body. In addition, estradiol stimulates the activity of antioxidant enzymes, such as glutathione peroxidase, in mitochondria. Since mitochondrial respiration produces reactive oxygen species that cause oxidative damage, this activity of estradiol results in less oxidative stress from normal metabolic processes (this may contribute to the longer life expectancy of women compared to men). Estrogen can also stimulate muscle repair and regenerative processes, likely by acting as antioxidants and mitigating oxidative damage, leading to greater muscle strength and preventing fall-related fractures.
Ideal estradiol levels vary for men and women, ranging in men from about 10 to 82 pg/ml (one pg or picogram is one one-trillionth of a gram).
Levels in women vary depending on which point of their menstrual cycle they are in:
- Less than 50 pg/ml during menstrual periods.
- Up to 200 pg/ml during follicular development.
- Up to 400 pg/ml just before ovulation.
In women, estradiol levels dip just before the release of the ovum and peak again during the luteal phase. If a woman is not pregnant, estradiol levels reach their lowest point at the end of the luteal phase.
There are a few options for testing levels of estrogens and estradiol, but they’re not all created equal. Blood testing is the least effective method because it only provides a snapshot of what your hormones levels look like at the exact moment you had your blood drawn. Since your hormone levels change throughout the day based on your normal circadian rhythm, this doesn’t give you a full picture. A salivary panel, known as an adrenal stress index (ASI), can measure salivary levels of hormones with four to five salivary measurements performed throughout the day. This gives you a more accurate idea of how your hormones are fluctuating during a 24-hour period.
The gold standard for hormone testing is a urine test known as the DUTCH test, which tells you not only what your hormones are doing over a 24-hour cycle but also the upstream and downstream metabolites of those hormones. This allows you to know if you are deficient in certain hormones, if your hormones aren’t being metabolized properly or if they’re being metabolized too rapidly. You can order a DUTCH test here (search for DUTCH Cycle Mapping + DUTCH Complete-Precision Analytical Inc. Kit) and an adrenal stress index here.
3. High-sensitivity C-reactive protein
Over two dozen research studies have proven that baseline levels of the inflammatory marker C-reactive protein (CRP) in healthy men and women are highly predictive of future risk of cardiovascular ailments, including heart attack, diabetes, stroke, sudden cardiac death, and peripheral arterial disease. It has also been shown that CRP levels predict repeat coronary events among patients who already suffer from heart disease and that the outcome of patients immediately after a heart attack is tightly linked to CRP levels.
Ultimately, individuals with excessive levels of CRP have a risk about two to three times higher than the risk of those with low, optimal levels.
In my opinion, a CRP test for inflammation, combined with a basic lipid panel, is the single best way to evaluate your risk for heart disease. By eating a diet high in anti-inflammatory herbs, spices, and nutrients (especially turmeric and fish oil) and avoiding overtraining and excessive stress and toxin exposure, I personally try to keep my CRP below 0.5 mg/L and prefer to have it below 0.2mg/L.
You can order a CRP test through your doctor or healthcare provider, through Amazon, or through an independent lab, such as DirectLabs, which offers tests that cover both CRP as well as lipids like HDL and LDL cholesterol and triglycerides.
4. Triglyceride-to-HDL Ratio
Otherwise known as the atherogenic index of plasma (yep, that’s a mouthful), a high triglyceride-to-HDL ratio (meaning a high number of triglycerides relative to your HDL cholesterol) is also one of the best indicators of your risk for heart disease.
This test has the added benefit of predicting lipoprotein particle size and insulin resistance, two other important markers for longevity.
For example, in one study in elderly women, the triglyceride-to-HDL ratio predicted all-cause mortality, meaning it predicted the risk of not only cardiovascular mortality but also the overall risk of dying from anything. There is, of course, a host of additional studies on this ratio, including a study that shows that triglyceride-to-HDL ratio predicts coronary heart disease and cardiovascular disease mortality risk as well as or better than full-blown metabolic syndrome. A ratio of 2 or under is good for a triglyceride-to-HDL ratio, and most of my healthiest clients and myself aim for 1 or under. Above 4 is typically a very unfavorable scenario.
In a nutshell, consider the following three variables as the biggest issues to pay attention to for your overall lipid and cholesterol scenario:
- Trends: Triglycerides should ideally go down over time, while HDL should trend upwards.
- Total Cholesterol (more details below):HDL-C ratio – Lower is better and usually indicates fewer atherosclerotic LDL particles.
- Triglyceride:HDL-C ratio – Lower is better and usually indicates larger LDL and fewer particles. Ideally, this ratio should be close to 1 or lower.
If your triglycerides are high, implement the following strategies:
- High intake of monounsaturated and omega-3 fats with low sugar and starch intake (e.g. low-carb Mediterranean-style diet)
- Vitamin C
- Fish oil or krill oil
- Olive oil
- Fenugreek seeds
- Prebiotics, probiotics, and synbiotics from fermented foods and supplements
- Fruit consumption (in moderation, preferably from small, darkly colored berries)
- Exercise before meals (particularly brisk walking)
If your HDL is low, implement the following strategies:
- Olive oil
- Low carb or ketogenic diet
- Anthocyanin-rich foods (e.g. blueberries, blackberries, pomegranate, eggplant, red cabbage, and other darkly colored fruits and vegetables)
- Low-to-moderate alcohol consumption
- Coconut oil
- Fatty fish
- Aerobic exercise
HDL and triglyceride levels can be measured by your doctor, but you can also order panels yourself through LabCorp or DirectLabs, then compare the results of the HDL panel to the triglycerides panel to determine your ratio. HDL and triglycerides are also typically measured on a lipid panel, which you are about to discover.
5 & 6. Full Lipid Panel And Omega-3 Fatty Acids
An advanced cardiovascular and lipid panel goes beyond the typical cholesterol test to help uncover early risk factors for heart disease. Most people may not realize it, but a cholesterol test is important way before you feel old or sick. A basic lipid panel measures fats and fatty substances in the blood, such as LDL, HDL, triglycerides, and total cholesterol, that indicate current and potential heart health, while a full lipid panel goes far beyond typical blood tests and includes a particle size measurement.
Particle size is crucial because research has shown that small, lower-density LDL cholesterol can be inflammatory and toxic to blood vessels and that a high level of lipoprotein(a) indicates the presence of the most dangerous blood lipids.
This Lp(a) is a specific type of small LDL cholesterol particle that inflames your blood and makes it “sticky,” and patients with Lp(a) are more prone to clotting. A comprehensive lipid panel can investigate the types of cholesterol particles in your blood and give you a far more accurate profile of your cardiovascular risk than standard cholesterol tests.
In most cases, a doctor or medical textbook will give you the usual, dyed-in-the-wool, one-size-fits-all advice for cholesterol ranges, such as the following:
- Total cholesterol: less than 170 mg/dl for those under 20 years old, and less than 200 mg/dl for those 20 years or older.
- HDL cholesterol: greater than 45 mg/dl for those under 20, and greater than 40 mg/dl for those 20 or older. In women aged 20 or older, values are greater than 50 mg/dl.
- Triglycerides: less than 75 mg/dl for those 9 years or younger, less than 90 mg/dl for those 10 to 19, and less than 150 mg/dl for those 20 or older.
- LDL-cholesterol: less than 110 mg/dl for those under 20, and less than 100 mg/dl for those 20 or older.
- Cholesterol-to-HDL ratio: less than 5.0 mg/dl.
- Non-HDL cholesterol: less than 120 mg/dl for those under 20, and less than 130 mg/dl for those 20 or older.
While these numbers are approximations of ranges for improving health or avoiding cardiovascular disease in a generalized population, the fact is that cholesterol values tend to highly fluctuate based on diet, exercise, genetics, and lifestyle. For example, Dave Feldman, of CholesterolCode.com, has developed a new paradigm for understanding cholesterol. Dave began demonstrating very large changes to his lipid markers through a series of self-experiments in which he changed only his dietary fat intake and kept every other lifestyle- and exercise-related factor constant.
His so-called Feldman Protocol has now been replicated by over 200 people who follow his work. The protocol involves eating a high-fat, low-carb diet with large quantities of fatty food for a few days, and the results from most people show, paradoxically, a corresponding drop in total and LDL cholesterol numbers.
Dave refers to this as an Inversion Pattern, and his lipid energy model suggests that high intake of dietary fat, especially when that fat is being used for energy by a very active person, can cause the production of LDL by the liver to go down because fewer lipoproteins are needed to transport fatty acids through the body and because triglycerides and fatty acids are being used so rapidly as a fuel.
In other words, lean, active people eating a high-fat diet may see their LDL decrease.
But this may not matter anyway because LDL can actually be a poor measurement of risk when compared to two other important lipid markers: HDL cholesterol and triglycerides. In studies that stratify all three, HDL and triglycerides appear as the clear risk indicators, with LDL becoming nearly irrelevant. When HDL is high and triglycerides are low, risk for cardiovascular disease is very low, regardless of LDL levels.
Ultimately, cholesterol can be confusing. If you want to become a cholesterol expert and understand forwards and backwards everything you need to know about lipids, I highly recommend my friend Dr. Peter Attia’s “Straight Dope On Cholesterol” series (see part 1 here, part 2 here, part 3 here, part 4 here, part 5 here, part 6 here, part 7 here, part 8 here, and part 9 here ) and his 5-part interview series (see part 1 here, part2, part 3, part4, and part 5) with Dr. Thomas Dayspring, both available at PeterAttiaMD.com. As discussed heavily in that series, particle count and size are particularly important, and your lipid panel should ideally be an NMR panel that can actually identify this (an NMR test is an FDA-cleared blood test that directly measures the amount of LDL circulating in the body, and directly counts the number of LDL particles a patient has using nuclear magnetic resonance technology). Ideally, total LDL particles should be less than 1000 nmol/L, total small LDL particles less than 600 nmol/L, LDL size greater than 21 nm, HDL size greater than 9 mmol/L and VLDL less than 0.1 nmol/L.
In addition, the fatty acids present in your blood are worth examining because a higher proportion of omega-6 linoleic acid can result in lower longevity and predict earlier death and physical and cognitive decline. This is because linoleic acid can make red blood cells more susceptible to oxidative damage, which ages the cells and impairs their ability to deliver oxygen.
In contrast, the more omega-3 fatty acid in the red blood cells, the lower your risk for colon cancer (and the higher the omega-6, the higher the risk for colon cancer). Older individuals with low levels of omega-3 fatty acids decline physically more quickly than older adults with higher levels. A low omega-3 fatty acid count also predicts smaller brain volume and cognitive decline, even in older adults who don’t possess any other symptoms of dementia. The ideal dietary ratio of omega-6-to-omega-3 fatty acids is 4-to-1, although many anti-aging and functional medicine practitioners suggest consuming a 1-to-1 ratio or higher in favor of omega-3 (the average American eats a ratio ranging from 12:1 to 25:1 omega-6-to-omega-3!)
There is also an important caveat. The omega-6 fatty acid in plant and vegetable oils is linoleic acid, but the omega-6 fatty acid that you ultimately use in your body and that you get from animal foods is arachidonic acid. The omega-3 fatty acid that is found in plant and vegetable oils is alpha-linolenic acid, but the omega-3 fatty acids that you get from animal food that you ultimately use in your body are EPA and DHA.
Now here’s one thing that a lot of folks don’t realize: despite plenty of talk out there about the ideal omega-6-to-3 ratio, most of the ratio data is based on animal experiments in which the animals were only fed fats found in plant and vegetable oils, specifically the linoleic omega-6 fatty acid and the alpha-linolenic omega-3 fatty acid. The ratio mattered quite a bit in these animal experiments – the enzymes that convert the omega-6 into the forms we need are the same as the enzymes that convert the omega-3s. So if there is not a dietary balance between omega-6 and omega-3, the fats can compete for those enzyme systems and too much intake of one fat may hurt the conversion of the other (and vice versa) and result in an omega-6-to-3 imbalance. But it’s important to understand that unless you’re a vegan who is only getting oils from plants, this doesn’t matter because the type of arachidonic acid and DHA found in animal foods, particularly foods such as eggs, liver and fish (and, even if you are a vegan, algae) won’t compete for the enzyme system because it doesn’t need any conversion.
So, ultimately, you need to pay more careful attention to omega-6-to-3 ratios only if you are eating a vegan diet.
An Omega index test is offered by labs such as Omegaquant, Great Plains, Quest or WellnessFX. This test examines EPA and DHA in red blood cell membranes, then calculates an index. For example, if you have 64 fatty acids in a cell membrane and 3 are EPA and DHA, then you would have an Omega-3 Index of 4.6%. An index of 8% or higher is ideal. Most people’s index is around 6% or below and in the US, most people are at 4% or below – the highest risk zone. This translates to a 90% higher risk of sudden cardiac death!
Finally, your stearic-acid-to-oleic-acid ratio, also known as your saturation index, is another important marker to check. Stearic acid is a saturated fat, and oleic acid is a monounsaturated fat. A lower saturation index is linked to several aging-related diseases, including non-alcoholic fatty liver disease, prostate cancer, colon cancer, and gallbladder cancer. When it comes to longevity, a higher amount of stearic acid is preferred. The normal index for both adults and children is 0.97 to 1.02.
These type of lipid panels can be ordered through your doctor or healthcare provider or through independent labs like DirectLabs and LabCorp.
7. Testosterone & Free Testosterone
Several reports published in the related medical literature have proven that low testosterone (low T) is associated with increased mortality.
They include a study that shows that low T levels are associated with increased mortality in male veterans.
Another study shows that low T is associated with increased mortality over a 20-year timespan, independent of metabolic syndrome, diabetes and prevalent cardiovascular disease (but attenuated by adjustment for IL-6 and C-reactive protein, making yet another case for keeping your inflammation low, especially if you have lower T). One report concludes that low T may be even more dangerous than previously thought and lead to a greater risk of death.
In that final report, men with low T had a 33% greater death risk over their next 18 years of life compared with men with higher T. The study tracked nearly 800 men, 50 to 91 years old, living in California. Their T levels were measured at the beginning of the study, and their health was then tracked over the next 20 years. In addition, low T can drastically affect the quality of your life as you age, as symptoms reported by these men included decreased libido, erectile dysfunction, fatigue, loss of strength, decrease in bone density and decreased muscle mass. These men tended to be overweight or obese and had higher risks for cardiovascular disease and diabetes. Indeed, men with the lowest T, below 241 total serum level, were 40% more likely to die!
Once T is produced by the testes (in men) or the ovaries or adrenal gland (in women), it enters the bloodstream as free T, which is the bioavailable form of T that your body can use. Normally, about 98% of this free T is bound to either albumin or sex hormone-binding globulin (SHBG). While about 55% of albumin-bound T can be used, SHBG-bound T is not readily bioavailable.
When it comes to T deficiencies, it is important to understand that having high total T levels does not mean that you will also have high, bioavailable free T levels. Some men have total T levels ranging from 300 to 800 ng/dl, but their free T levels are often as low as 2, 3 and 4ng/dl (often less than 1% of total T!). This can occur because some of the 2% of your T that remains in a free form can be converted into hormones like estradiol and DHT.
While you do need some amounts of estradiol and DHT (DHT is especially important in the brain as it promotes neurogenesis), when too much of your free T is converted into these hormones, you can suffer from the low bioavailable T levels that are associated with the health issues outlined above and an increased risk of death. This excess conversion is often associated with deficiencies in minerals like lithium, magnesium, and manganese, so you should ensure that you include as dietary staples sources of these minerals, such as nuts, dairy, red meat and leafy greens for lithium; legumes, avocados and dairy for magnesium; and whole grains, nuts and leafy greens for manganese).
So what ratio of free T to total T should you aim for?
Ideally, you want at least 2% of your T to be free, and this usually means that as a ratio, your T levels should be at least 1-to-49 free-T-to-bound-T. In other words, if your total T is, say, 500 ng/dl, then your free T levels should be about 10.2 ng/dl. The upper accepted levels for free T peak at 27 ng/dl, but it is important to note that this upper limit is simply the result of available measurements that have been performed and does not come from any reference range for what the maximum amount of testosterone is that a healthy human can maintain. This is why it is important to also pay attention to qualitative variables like libido, recovery and erectile function.
For men, ideal levels of free T typically range from 4.6 to 22.4 ng/dl, and ideal levels of bioavailable T (which includes albumin-bound T and free T) range from 110 to 575 ng/dl. For women, ideal levels of free T range from 0.02 to 0.5 ng/dl, and ideal levels of bioavailable T range from 0.5 to 8.5 ng/dl. You can delve into even more resources on the link between T and overall health and longevity in a fascinating article by Dr. Jeffrey Dach.
If you are testing your testosterone levels, it can be insightful to also test DHEA. The largest amount of hormone produced by the adrenal glands is actually in the form of DHEA, which is a precursor to estrogen, progesterone, and testosterone. Symptoms of DHEA deficiency usually include fatigue, tiredness, exhaustion, cognitive impairment, depression, decreased libido, and risk of recurrent infections.
Fortunately, DHEA is relatively easy to measure. But when DHEA is measured, the results should be correlated to age to be meaningful. Males around the age of twenty should have high levels of DHEA (around 1,200 ng/dL). By age ninety, the level is usually closer to 180 ng/dL. A thirty-year-old male with a DHEA level of 250 ng/dL would technically fall “within the normal range” of 180 to 1,200, but as you can imagine, this is a problem, since it’s nowhere near optimal levels and can actually indicate adrenal insufficiency and significant hormone imbalances.
Similarly to estradiol and estrogen testing, the best way to test testosterone levels is not via a blood test or salivary test (although salivary tests are more accurate than blood tests if performed 4 to 5 times throughout the day), but via a comprehensive DUTCH test.
In a recent interview with the blood-testing company WellnessFX, Dr. Rhonda Patrick said, regarding insulin-like growth factor-I (IGF-I), that:
“…in some cases there may exist a trade-off or a ‘Faustian bargain’ between longevity and performance. Optimizing for IGF-1, otherwise known as insulin-like growth factor-1, is one such case where more performance driven goals like maximizing growth and maintaining muscle and neurons may, to some degree, come at odds with one’s desire for longevity.
The reason for this is that, aside from IGF-1’s more notorious role in building muscle, it has been shown to have some very interesting properties that haven’t entered mainstream dialogue as of yet: mice deprived of IGF-1 live longer…finding safe and effective ways to increase growth hormone and IGF-1 naturally, thereby, improving muscle and brain function while simultaneously preventing their atrophy seems like a no-brainer, who doesn’t want to be more fit and smarter – for longer?
Or is it longer? Mice, worms, and flies that are genetically engineered to be deficient in either growth hormone or IGF-1 live almost 50% longer than controls, which is a huge increase in lifespan. The converse has also shown to be also true: Overexpressing growth hormone by 100 to 1,000-fold in mice causes a 50% shorter lifespan, mainly due to kidney and liver dysfunction. The same results have been demonstrated in lower invertebrate species such as worms and flies, suggesting that this mechanism is evolutionarily conserved.
Okay, admission here: either eliminating growth hormone or blasting it 1000-fold in mice is rather extreme… If you’re not quite convinced that the aging component to all of this is something that might also be relevant to humans consider this: polymorphisms (variations) in the gene that encodes for the IGF-1 receptor, which leads to decreased IGF-1 levels, have been associated with the longer lifespan found in centenarians.”
Ultimately, while the anecdote above sums things up pretty thoroughly, recommended levels of IGF can vary widely, but in an eye-opening hormone replacement therapy podcast interview I conducted with anti-aging physician Dr. Richard Gaines, he recommended a sweet spot of IGF-1 values between approximately 80 and 150 ng/ml. You can order an IGF-1 blood test online through LabCorp or Lab Tests Online.
Low fasting insulin can be a crucial marker for longevity and indicates an important variable called glycemic variability, which is how often your blood sugar levels fluctuate throughout the day.
For example, high fasting insulin levels are associated with a greater risk of cancer mortality.
In addition, cancer patients who eat the highest amount of insulin-producing foods experience worsened cancer and increased overall mortality. Furthermore, high insulin levels can predict cancer mortality, even when controlling for variables such as diabetes, obesity, and metabolic syndrome. In older adults with type 2 diabetes, the level of insulin use also predicts mortality.
The trick is not to eliminate insulin altogether, but to keep insulin levels within certain limits. My friend Dr. Joseph Mercola recommends “a normal fasting blood insulin level…below 5 [uIU/ml], but ideally… below 3.” You can order a blood insulin test through your doctor or healthcare provider or online through LabCorp or DirectLabs.
10. Complete Blood Count with Differential
A complete blood count with differential, also known as a CBC, is often used as a broad screening test to determine an individual’s general health status. It can be used to screen for a wide range of conditions and diseases and to help diagnose various conditions, such as anemia, infection, inflammation, bleeding disorder, or leukemia.
The CBC is a panel of tests that evaluate the three types of cells that circulate in the blood, including:
-The evaluation of white blood cells, the cells that are part of the body’s defense system against infections and cancer and also play a role in allergies and inflammation. White blood cell (WBC) count is a count of the total number of white blood cells in a person’s blood sample and identifies and counts the number of the various types of white blood cells present (the five types include neutrophils, lymphocytes, monocytes, eosinophils, and basophils).
-The evaluation of red blood cells, the cells that transport oxygen throughout the body. Red blood cell (RBC) count is a count of the actual number of red blood cells in a person’s blood sample. Other factors in this part of the panel include hemoglobin, MCV, MCH, MCHC, RDW, MPV, and PDW. Hemoglobin measures the total amount of the oxygen-carrying protein in the blood, which generally reflects the number of red blood cells in the blood. Hematocrit measures the percentage of a person’s total blood volume that consists of red blood cells. Mean corpuscular volume (MCV) is a measurement of the average size of a single red blood cell. Mean corpuscular hemoglobin (MCH) is a calculation of the average amount of hemoglobin inside a single red blood cell. Mean corpuscular hemoglobin concentration (MCHC) is a calculation of the average concentration of hemoglobin inside a single red blood cell. Red cell distribution width (RDW) is a calculation of the variation in the size of RBCs. The mean platelet volume (MPV) is a calculation of the average size of platelets. Platelet distribution width (PDW) reflects how uniform platelets are in size.
In the article “Which observations from the complete blood cell count predict mortality for hospitalized patients?”, it is reported that the most impressive predictors of mortality to be derived from a CBC are burr cells, nucleated red blood cells (NRBCs) and absolute lymphocytosis (an increase in the number of lymphocytes in the blood). In the analysis, the first two (burr cells and NRBCs) were associated with mortality rates 8 to 10 times higher than that of the average admitted patient. There are anecdotal reports in the literature of burr cells being associated with “ominous prognosis” and more robust statistical analyses showing NRBCs to be associated with increased mortality. Lymphocytosis has also been reported as a mortality risk in patients, especially those with trauma and emergency medical conditions. The analysis shows that all three of these findings are strong, independent predictors of mortality.
In addition, one study reports that men and women with above-normal WBC counts could face an increased risk of death at an earlier age, particularly from cardiovascular disease. People with normal WBC counts may not be out of danger since individuals on the high end of the normal range are also at increased risk of illness and death. Basically, the risk of cardiovascular mortality increases progressively with increasing WBC counts, and the increased risk of mortality associated with high WBC counts is maintained over 40 years of follow-up!
For WBC counts, a healthy blood functional range is between 5 and 8 cells per liter. Higher often indicates a possible infection and lower often indicates a depressed or suppressed immune system. As mentioned above, consistently high WBC counts translate to an increased risk of death at an earlier age, particularly from cardiovascular disease.
- Neutrophils – 40-60%. 25-40%. Higher = viruses, autoimmunity, or detoxification challenges.
- Monocytes – 0-7%. Higher = liver dysfunction, prostate problems, or recovering from infection (or Epstein Barr virus).
- Eosinophils – 0-3%. Higher = food sensitivities, environmental allergies, or parasites.
- Basophils – 0-1%. Higher = histamine intolerance.
You can order a CBC through your doctor or medical provider or order it online through LabCorp or DirectLabs.
Iron is certainly an important nutrient for almost all life. It forms hemoglobin, making it necessary for the effective transportation of oxygen in blood. It comprises proteins throughout the body and regulates cell growth and differentiation. It even helps maintain brain function, metabolism, endocrine function, and immune function and plays a role in the production of ATP, your body’s primary energy source.
But while iron seems to be the darling of many in the health and medical industries and iron deficiencies are frequently tested for, iron toxicity is rarely addressed.
As a result of many people being convinced that iron is a panacea, it can be found in everything from multivitamins to fortified, whole-grain breakfast cereals. Problem is, if you consume too much iron, you can develop iron overload. There’s even a disease called hemochromatosis, which is characterized by an accumulation of dangerously harmful levels of iron. This can be an especially concerning issue for men, who don’t bleed as regularly as women, and for sedentary individuals, who don’t turn over as many red blood cells and as much iron as active individuals, particularly endurance athletes.
Basically, as your cells produce energy through normal metabolism, they produce low, manageable levels of a toxic byproduct of oxygen called superoxide. As superoxide is produced, enzymes convert it into hydrogen peroxide, which is then converted into water and oxygen. But when iron interacts with superoxide or hydrogen peroxide, it leads to a chemical reaction that produces a free radical known as a hydroxyl radical.
Hydroxyl radicals can be extremely harmful to your cells, and if you are consuming excess iron or have excess iron in your bloodstream, you can produce high levels of these radicals, leading to age-related chronic conditions such as can cancer, heart disease, diabetes and neurodegenerative conditions like Alzheimer’s and Parkinson’s. Think of this like “rusting” your body.
There are two biomarkers you can track that will reveal if you have excess iron, the first being a protein called ferritin.
When your iron levels are sufficient, the protein hepcidin is secreted by the liver and signals to the cells in your gastrointestinal tract to block the absorption of iron. It also signals your body’s other cells to bind their iron to ferritin, which acts as an iron storage mechanism. If your ferritin levels are high, then you may have too much iron in your body and can run the risk of oxidative damage to your cells and mitochondria. People with hereditary hemochromatosis have a genetic inability (based on their “HFE” gene) to effectively use hepcidin to regulate iron levels, so they are highly susceptible to iron overload.
A typical reference range used by most laboratories for ferritin ranges from 200 to 300 ng/mL for women and men respectively, but the actual ideal levels for adult men and non-menstruating women are between 30 and 60 ng/mL, and you don’t want to be below 20 ng/mL or above 80 ng/mL.
If you’re a woman and are still menstruating, you are more likely to suffer from iron deficiency than iron overload, so if you experience fatigue, paleness, shortness of breath, headaches, dizziness, heart palpitations, dry or damaged hair and skin, restless legs or mouth swelling during your period, you likely need to consume more iron. If you have no symptoms, and your biomarker levels are within the ideal range, then your iron levels are probably being sufficiently regulated by your menstrual cycle. If you’re a man, you’ll likely only experience issues with low ferritin or low iron if you’re a heavily training athlete or you’re not eating any red meat.
Another biomarker to track for iron is gamma-glutamyltransferase (GGT).
GGT is a liver enzyme involved in the metabolism of the antioxidant glutathione, as well as the transport of amino acids and peptides. Originally tracked to determine the extent of alcoholism and liver damage, GGT is also highly interactive with iron and can be used to track levels of excess free iron (unbound iron in your blood). In fact, GGT was recently shown by experts in the health insurance field to be the single most predictive measure of early death by any cause. If you have both high ferritin and high GGT, you have a significantly increased risk of chronic disease because it means that you have both excess free iron (indicated by GGT) and excess stored iron (indicated by ferritin) that keeps those free levels elevated.
Similarly to ferritin, the reference ranges that are considered “normal” in men and women are not the ideal levels. In men, “normal” GGT levels are allowed to range all the way up to 70 U/L (units per liter), but ideal levels are less than 16 U/L. For women, normal levels range up to 45 U/L, while ideal levels are less than 9 U/L.
You can request ferritin and GGT tests through your doctor or order them online via LabCorp or DirectLabs. Conveniently, to reduce excess iron levels, all you need to do is give blood two or three times per year, reduce your intake of red meat, or take up some form of frequent cardiovascular exercise, or all three. Men and postmenopausal women are particularly at risk for developing iron overload since they don’t lose a significant amount of blood once per month, so if you fall into one of those two categories, then consider giving blood a few times per year. If you can’t give the liter of blood that’s normally drawn, then you can have 2 to 6 ounces of blood drawn once every few weeks.
So there you have it.
Sure, you should certainly pay attention to qualitative, objective variables such as love, life, relationships, healthy food, fasting, grip strength and more. But you should also use modern science to track important internal variables and the biomarkers you have just discovered in this new anti-aging panel.
If all this testing sounds a bit overwhelming, then please realize that the goal is not to spend each day hunched over a tube while spitting saliva, filling beakers full of blood in a laboratory or pooping into a tray every time you use the bathroom.
In contrast, a simple and ideal yearly self-quantification scenario would look like this:
- DNA test such as 23andMe: once in a lifetime
- Comprehensive blood test such as Greenfield Longevity Panel for men or women: once per year
- Gut microbiome test (e.g. Viome or Onegevity code: BEN20 will save you $20) or stool panel (e.g. Genova Diagnostics 3 Day Panel): once per year or whenever the gut seems to significantly change in function or health.
- DUTCH test: once per year or if feeling fatigued/run down with no explanation, particularly if low libido.
- Food allergy test such as Cyrex: once per year or whenever the gut seems to significantly change in function or health.
- Readiness and sleep tracking via something like the Oura ring: daily
- Ketones (use code: KION to save $25) and glucose testing (see my article on this here): optional, but to be performed ideally on a daily basis when adopting a new diet or when attempting to evaluate which food groups cause glycemic variability or a rise/fall in ketones
- Micronutrient test such as Genova ion panel with 40 amino acids: optional, but to be performed if concerned about energy levels, health issues, or wanting to “dial in” supplementation and diet protocol even more thoroughly.
The only blood test not included above but that I still highly recommend if your goal is to track your biological aging process is a telomere analysis. You can learn more about that test, and telomeres in general, in this comprehensive podcast with Dr. Bill Andrews here.
Do you have questions, thoughts or feedback for me about self-quantification, longevity, or anything else you’ve discovered in this article? Leave your comments below and I will reply!
12 thoughts on “The 11 Best Biomarkers To Track If You Want To Live A Long Time & Feel Good Doing It.”
How does Alcat, MRT, and Cyrex compare for you?
This is a great article, thanks so much. I’m extremely keen to get a blood test done that’s as near to comprehensive as the longevity panel that you provide in the US. Many Thanks, you became my favourite author!
If I were to show this list to a Primary Care Physician, would he or she be able to order all these test up for me? How much would these tests cost in a city like New York?
Thank you for your time.
The mention of free testosterone and depleting lithium helped answer a huge question for me. A family member with post concussion syndrome for 18 months saw obvious massive improvements after starting a lithium orotate supplement. We never understood why. The link to Dr. Dach’s article completely explains it. Why isn’t this supplement being used more? (like many good supplements)….Thanks much!
Link to article: https://jeffreydachmd.com/2015/12/lithium-orotate-neuroprotection-part-two/
Where can I get the longevity test done or telomeres near Los Angeles, California? I want to see if NAD has improved my age.
Hey Ben – thanks for the great info. Recently completed a DUTCH test. Wanted your thoughts on something. The following metrics were “below the optimal range”: Estrodiol (E3), DHEA, and Epi-Testosterone while the following metrics were “above the optimal range”: b-Pregnanediol, Testosternone, 5a-DHT and 5b-Androstanediol. I’m a 30 year old male. Based on your comments re. DHEA, I’m assuming I have a hormone imbalance. If you agree, what would be your recommendation(s) for ameliorating the situation and getting back to “baseline”? Thanks.
Hey Ben, another great article,thanks so much. I’m extremely keen to get a blood test done that’s as near to comprehensive as the longevity panel that you provide in the US, but I’m living in europe. Do you have recommendations for companies operating with the UK or Central Europe that would provide a high-standard, home test service? Many Thanks, Cameron
I recommend posting this to the Kion Community. It’s a completely free online community of like-minded people who both have advice and are seeking advice. Facebook.com/groups/GetKion/
Several of the tests you recommend as part of the annual testing one should complete are only available to those located in the United States.
Are there alternatives available people located in Canada for the Greenfield Longevity Panel from WellnessFX?
The Dutch Test from WellnessFX?
The Cyrex testing from True Health Labs?
I second Rainer’s opinion! Your writing is impeccable and while thorough and scientific, it is very easy to understand. This is rarely the case with others attempting to discuss complicated health subjects. Ben, you are absolutely the first one I check with on health matters! Thank you so much for all you do!
do you know of any comprehensive blood tests comparable to yours that is available in Australia?
Your best article so far in my opinion. Excellent ,comprehensive and flawless information. Truly brilliant !
Just had a look at Dr. Thomas Dayspring. The cardiology test at True Health Diagnosis clearly surpasses those
of highly acclaimed clinics such as Mayo Clinic and Cleveland Clinic. However I could not find that True Health
Diagnosis checks for plasma ceramides,which is done by Mayo Clinic. Plasma ceramides are an interesting topic:
Your articles,which show your love for both research and word fluency are always a joy to read
Greetings from Switzerland to the magnificent meticulous health humanitarian