Screening Laboratory Tests for Runners, Part 2

Direct-to-consumer lab testing is a rapidly growing industry which allows adults to order their own blood testing without involving a physician or other health-care practitioner. LabCorp, Quest Diagnostics, and InsideTracker are all examples of these companies. This is the second article in a two-part series of two about direct-to-consumer laboratory testing for runners.

In the first article, I recommended against screening laboratory testing of asymptomatic runners because:

1. The risk of getting an abnormal result when a person is actually normal is too high (5% per test) and causes unnecessary worry and/or retesting; and
2. Research on this topic (1, 2, 9) has shown that the chance that an otherwise healthy athlete will uncover an abnormal result that can be corrected to benefit their health or performance is very low.

For this reason, I decided to not have myself retested for the second article–Bryon Powell and I were both tested by InsideTracker for the first article. For this second article, I had patient Farah Avasarala tested because of her ongoing health issues. Case #2 in this article is a follow-up with Bryon Powell who had a very unexpected health problem identified in his first round of testing.

Case #1: Farah Avasarala

For Farah Avasarala, it started on a trip to India in 2018. Something wasn’t right. Farah was in her mid-forties and had finished her first ultramarathon at the 2018 Quicksilver 100k. She felt strong, had a decent training build-up to the race, and no health issues that she knew of.

Figure 1: Farah Avasarala at the 2017 Broken Arrow Skyrace. Photo: Jesse Ellis/Let’s Wander Photography

She had a good summer following that and returned to her usual training regimen feeling strong. Then, on a vacation to India in September of 2018, she developed gastrointestinal (GI) issues, fatigue, and joint and muscle pain. She continued to push through her normal training and, over the next one to two months, developed “progressively worsening fatigue and pain.”

Initial laboratory testing showed entirely normal blood counts of electrolytes, white blood cells, inflammatory markers (ESR and CRP), thyroid, and liver and kidney function without evidence of infection, inflammation, or iron deficiency. Creatine kinase (CK), a marker of skeletal muscle breakdown, showed no evidence of muscle breakdown. Her GI symptoms continued, so she was prescribed an antibiotic for a presumed Giardia infection and they soon improved. However, she continued to have fatigue and pain in her muscles and joints. She reached out to me for advice in November of 2018. She stated then, “I am wondering if I had pushed training when I should have backed off and rested.”

At that time, laboratory testing showed a lower than normal white blood cell count (3.4 thousand/uL; normal is 3.8 to 10.8) and a very low vitamin D level (14.9 ng/mL; normal is 30 to 100). I wondered if the low white blood cell count was due to some lingering viral infection, her vitamin D deficiency, overexertion, or all of the above. Also, low vitamin D could also be due to infection, inflammation, or suboptimal health in general. All testing for infection was normal. However, given her initial infectious symptoms and persistent and severe fatigue, I mentioned the possibility of post-infectious Chronic Fatigue Syndrome (CFS). She was the one who pointed out a very well done study which found that 5% of people in Norway diagnosed with Giardia went on to develop CFS. CFS is a pathologic condition characterized by persistent and unexplained relapsing physical and cognitive fatigue that is worsened by physical and mental exertion (3) and tends to be accompanied by ongoing GI disturbances (10). However, as it lasts at least six months, it was too early to make this diagnosis. I recommended she start vitamin D supplements and made sure she had been taking probiotics (which she had) because of the antibiotic and possible CFS (10). We also discussed not increasing her training too quickly.

Two months later, she started to feel better and began rebuilding her fitness for the 2019 Canyons 100k. I saw she had finished and figured she was doing better, but then she reached out to me again this fall. She said that she didn’t feel well during the race and since then her symptoms returned. She stated she had great difficulty completing workouts that were previously easy. She had muscular pain in her thighs and would get dizzy easily.

She further explained, “I feel like it relates to energy storage and depletion. Like my body has nothing in it to do the work. My pace is far slower than it ever was. I have to mentally push myself as there’s nothing there physically, and the stress/pain/fatigue is not the same as when feeling well but simply trying to push beyond a threshold. I find that… my body fatigues quickly and I have to stop.” She also mentioned that she only trained for the Canyons 100k for six weeks and that she had an upper respiratory infection following the race.

I wondered what we would learn with InsideTracker’s ‘Ultimate’ panel. Here were her results:

Figure 2. Farah Avasarala’s Inside Tracker ‘Ultimate’ panel printout. The green dot means that the result is in InsideTracker’s “optimal zone,” the orange dot means “outside of optimal zone,” and the red dot is “abnormal.”

First, when I see these results, I think, How do consumers interpret these without the advice of a physician? Despite InsideTracker offering guidance on the results, I would be interested to see how many athletes who do this testing end up getting the advice of a doctor after receiving the results. Or how much worry is created when something is off?

There were three notable results in Farah’s blood work:

1. Suboptimal ferritin and transferrin saturation (TS) – These are measures of iron storage and are low for a female runner. Her symptoms certainly sounded like they could, at least partly, be due to iron deficiency, so I told her to start an iron supplementation of 65mg twice a day with vitamin C. Farah is a vegan menstruating female, so she is at high risk for iron deficiency. See our previous article on iron in athletes for more information, but runners have both a greater need for iron and go through it more quickly that other athletes and non-athletes. She had stage 1 iron deficiency based on suboptimal ferritin and her response to supplementation afterward.
2. Low white blood cell count – This made me wonder again about a lingering infection, but without an increase in leukocyctes, lymphocytes (both of these are white blood cell types that tend to increase with infection), or hsCRP* (this is hard to interpret as an inflammatory marker), this seemed highly unlikely. If anything, low lymphocytes can be a sign of exhaustion/overexertion and might be related to either non-functional overreaching or insufficient sleep or recovery in the face of possible CFS.
3. Mildly elevated CK – She had exercised just two days prior and CK can remain elevated for up to a week after exercise (6). Up to 30% of patients will still have abnormally high CK levels three days after exercise (6). CK levels one would see with a myositis (muscle inflammation due to infection or autoimmune disease) would typically be five to 50 times the upper limit of normal (so greater than 1,000 U/L). I thus felt comfortable attributing her mild CK elevation to recent exercise. Though, it also meant that the exercise she did two days ago was strenuous for her.

*hsCRP is not indicated for use as an inflammatory marker but instead is a marker for risk of heart disease. Fortunately, we had inflammatory markers ESR and CPR tested in Farah previously and they were normal, otherwise testing for these would have been needed to help rule out a rheumatologic or autoimmune condition.

Farah also added that she typically got six hours of sleep a night, had been experiencing decreased appetite on and off over the last year, and had a worsening of her usual atopic dermatitis rashes. She also explained her current training regimen:

• Running three times/week, including a track session and two hill-repeat sessions;
• Two gym sessions/week, and
• One to two tennis sessions/week.

I suspected she was training above her aerobic threshold (or above the onset of blood lactate accumulation) every time she ran, though had no ‘proof’ as she does not train with a heart-rate monitor or measure blood lactate. It is worth mentioning that, if she did have a CFS diagnosis, the illness causes an elevation in resting heart rate and heart rate during exercise (7) and, in many, abnormally elevated lactic acid levels at rest (4) and during exercise (5)–suggesting dysfunction at the level of the mitochondrium. These factors can push a person into a ‘strenuous’ workout faster than usual.

Based on all this and previously normal thyroid-function tests, I made the tentative diagnoses of stage 1 iron deficiency with overtraining/under recovery in the setting of probable post-infectious CFS which relapsed following an extremely warm and arduous 100k race. Six hours of sleep has been shown to be inadequate for proper recovery and health, especially in someone who exercises regularly. Learn more about athletes and sleep in our sleep-science article. Consistently training intensely above the aerobic threshold requires more recovery and is not as effective at building endurance as consistent aerobic-zone workouts. Based on this, I recommended she do most of her workouts at an effort where she can still carry on a conversation and/or wear a heart-rate monitor and not let her heart rate get above 70 to 75% her theoretical maximum heart rate while she is still recovering.

Following the initiation of iron supplementation and improved sleep, she experienced a sizable boost in her energy during exercise. At this time, I recommended a very cautious recovery and continued iron supplementation (at least once a day or every other day as GI side effects permit) until getting her iron panel rechecked in February of 2020 (three months after her first test). The importance of rest, recovery, good nutrition, and lower exercise intensity in a case like this cannot be overstated. I am also having her tested for gut infection and gluten allergy. Also, she continues to be at high risk for relapse if she ups her training regimen too quickly, especially in the face of inadequate sleep.

CFS is a diagnosis of exclusion and I will continue to work with Farah during her recovery to ensure we are not missing another cause of her symptoms. I know that some people are more severely affected by CFS and would not be able to run a 100k race. As CFS has a severity spectrum, I wonder if high-level athletes are more at risk for ‘unmasking’ a more mild CFS and thus are more at risk of developing it. At my last check-in with Farah in January of 2020, she stated, “My energy is much better and I am looking forward to exercise versus having to mentally push/motivate.”

Case #2: Bryon Powell

Bryon Powell, the 41-year-old Editor-in-Chief of iRunFar had an ‘Ultimate’ panel tested for the first article about direct-to-consumer laboratory testing. He had not been having any specific symptoms. However, he also did not have a primary-care doctor and due to high-deductible insurance had not had laboratory testing done in many years. He had also been unwittingly naughty in taking heavy-duty iron supplementation (65mg daily plus a multivitamin with iron) for at least a half a year without any known iron deficiency. While he did this because he had moved to higher altitude, iron supplementation in men can be dangerous because they do not have a built-in mechanism for getting rid of excess iron via a monthly menstrual cycle like women do.

When we received his first set of ‘Ultimate’ panel results, we learned, as he said, that he had been “poisoning [him]self.” Bryon was an unexpected example of how screening laboratory tests can be beneficial. The following are Bryon’s results from four screening tests:

Figure 3. A portion of Bryon Powell’s Inside Tracker ‘Ultimate’ panel printout. He was tested a total of four times between January and October of 2019. Multiple tests took place after a health problem was uncovered to monitor recovery from it. The green dot means that the result is in InsideTracker’s “optimal zone,” the orange dot means “outside of optimal zone,” and the red dot is “abnormal.” Some values from the first test are missing due to an error in the processing of his blood.

Here are the important notes from Bryon’s blood work:

1. Exceptional ferritin and transferrin saturation (TS) in his first test – This was when he was taking daily iron supplementation. It’s also interesting is how long it took these values to normalize, though it should be noted that he continued to supplement through February 4 of 2019 when he received the results and immediately stopped.
2. Delayed dip in free testosterone – This is interesting and also consistent with what would be expected with long-term iron overload causing testosterone deficiency. The reason for this is that excess iron builds up in many organs, including in the reproductive organs where testosterone is produced. Also, notably, iron build-up can occur in the liver and heart, which can lead to major illness.
3. Excess iron may have caused inflammation – Note his elevated cortisol level in the first test.
4. Hemoglobin levels don’t equate to iron levels – Many runners take iron to increase their hemoglobin levels, but Bryon’s hemoglobin actually increased when his iron level decreased to normal. The reason his hemoglobin was slightly lower when he was taking iron is not entirely clear to me, and this may not be a significant change, but it does demonstrate the point that more iron than a red blood cell needs will not increase hemoglobin or hematocrit.

Finally, we thank InsideTracker for testing Bryon and saving him from the major health problems he most likely would have developed had the supplementation continued. And maybe some readers will benefit, too.

Figure 4. Bryon Powell running the Ultra Trail Mt. Siguniang 110k race in November of 2019. He was feeling strong and healthy in this race and went on to take third place! Photo: KAILAS/Ultra Trail Mt. Siguniang

Summary

An ‘iron panel’ set of laboratory results was useful in all three runners tested during this set of articles, though for different reasons in each case. Iron deficiency is highly prevalent among female runners and all runners (both sexes) have an increased need for iron. You can read much more about this in our previous ‘Running on Science’ article about iron deficiency and anemia in runners. A large study looking at the prevalence of iron deficiency or overload in male and female ultramarathon runners has not yet been done and would be helpful in determining if iron panel levels should be routinely run on this subgroup of athletes. Iron panel laboratory results from 2019 Western States 100 runners are forthcoming.

Men and post-menopausal females should have an iron panel tested if they are considering iron supplementation. Menstruating female runners can likely safely take the amount of iron that is in a multivitamin, but should have an iron panel and/or complete blood count tested before taking a higher dose. If supplementation is started, repeat testing should be done every three to six months and supplementation should only continue while the deficiency persists. All males and non-menstruating females with iron deficiency should seek a physician’s guidance as there may be an underlying health problem causing the iron deficiency.

While InsideTracker offers many useful tests for runners and athletes in their ‘Ultimate’ panel, thyroid hormone levels, estradiol (estrogen), creatinine (a measure of kidney function), and ESR and CRP (markers of inflammation) are all missing from their package and would be important to measure in many athletes depending on their symptoms.

Based on the available research (1, 2, 9), specific laboratory testing based on symptoms is recommended over a screening panel. If a runner does order a screening panel, it is important to have a physician to go over the results with, especially if anything is found to be abnormal.

Runners should be aware that the creation of “optimal” ranges created by direct-to-consumer testing companies, rather than the more well-established normal ranges, encourages repeat testing. Optimal ranges suggest that an even narrower range of laboratory values may be associated with better health or performance, but the research behind these optimal ranges varies and what can be suboptimal for one person may be optimal for another. Rather than continuing to repeat testing or make major lifestyle changes based on suboptimal levels, it would be wise to consult with a health-care practitioner who is experienced in working with endurance athletes. The pursuit of “optimal” levels may be entirely unnecessary for good health and can be expensive.

The two cases covered in this article have however demonstrated that direct-to-consumer screening laboratory testing can be helpful to monitor iron levels and to assist in ruling out diagnoses of exclusion, but should be ideally be done alongside consultation with a health-care practitioner.

Call for Comments (from Meghan)

• Have you experienced direct-to-consumer laboratory testing?
• If so, can you share your experience?

References

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4. Ghali A, et al. Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Sci Rep. 2019 Dec 11;9(1):18817. doi: 10.1038/s41598-019-55473-4.
5. Lane RJM, Burgess AP, Flint J, Riccio M, Archard LC. Exercise responses and psychiatric disorder in chronic fatigue syndrome. BMJ. 1995;311:544–545. doi: 10.1136/bmj.311.7004.544.
6. Lilleng H, Abeler K, Johnsen SH, et al. Variation of serum creatine kinase (CK) levels and prevalence of persistent hyperCKemia in a Norwegian normal population. The Tromsø Study. Neuromuscul Disord. 2011;21:494–500.
7. Nelson MJ. Evidence of altered cardiac autonomic regulation in myalgica enchaphalomyelitis/chronic fatigue syndrome: A systematic review and meta-analysis. Medicine (Baltimore). 2019 Oct;98(43):e17600. doi: 10.1097/MD.0000000000017600.
8. Preidis GA, Versalovic J. Targeting the human microbiome with antibiotics, probiotics, and prebiotics: gastroenterology enters the metagenomics era. Gastroenterology. 2009;136(6):2015–2031. doi:10.1053/j.gastro.2009.01.072
9. Sanders B, Blackburn TA and Boucher B. Pre-participation screening – the sports physical therapy perspective. Int J Sports Phys Ther. 2013; 8: 180-193.
10. Venturini et al. Modification of Immunological Parameters, Oxidative Stress Markers, Mood Symptoms, and Well-Being Status in CFS Patients after Probiotic Intake: Observations from a Pilot Study. Oxid Med Cell Longev. 2019; 2019:1684198. Epub 2019 Nov 23.