Athletes frequently experience concussions. In fact, approximately 3.8 million sports-related concussions occur each year in the United States. The U.S. Centers for Disease Control estimates that 5-10 percent of athletes experience one concussion during a particular sports season.1 American football is associated with one of the highest incidence of concussions,2 also referred to as traumatic brain injury (TBI). With these alarming statistics, as a health solutions company, we can’t help but question whether nutritional or metabolic abnormalities in an athlete prior to entering a contact sport environment could adversely influence the clinical outcome if or when that athlete’s brain is subjected to a TBI.

My co-authors and I had the chance to seek answers to our questions on the biomarker status in a group of elite, soon-to-be professional football players. Recently published in the Journal of Strength and Conditioning Research, our study – “Molecular deficits relevant to concussion are prevalent in top-ranked football players entering the NFL draft” – sheds light on which specific biomarkers we found to be suboptimal in a group of football players, how prevalent the occurrence is, and how these biomarkers are relevant to brain health and function.14

The Observational Study

A small but elite group (n=30) of former American collegiate football players who were only four weeks post-completion of their final collegiate season volunteered for the study. Thirteen athletes were “big” defensive players or linemen; seven were “skill” players, including wide receivers, cornerbacks, safeties, return-specialists, or other; and 10 were “big skill” quarterbacks, running backs, halfbacks, tight ends, or fullbacks. Coming fresh off their college season, their average age, weight, height, and percent body fat were 22 years, 244 pounds, 6 feet 2 inches, and 16.4 percent, respectively. 

Twenty-one of the 30 athletes came from a college with a full-time performance staff dedicated to the football program, including athletic trainers, registered dietitians, and strength and conditioning coaches. These athletes prepping for the NFL draft were all-stars on their former teams and considered in the top 1.5 percent of athletes that transition from the NCAA to the NFL. They were training for the NFL Combine – the “camp” that assesses their athletic capabilities before entering the NFL draft. Twenty-five of them signed a contract with an NFL team a few weeks after this study.

Each athlete consented to a fasted but hydrated morning blood draw that included a targeted metabolome of 79 biomarkers selected based on their relevance to athletic performance, general health/well-being, and actionability to be optimized through nutrition. Relevant blood analytes included a full red blood cell (RBC) fatty acid analysis, lipid panel, hormones (estradiol, free testosterone, total testosterone, cortisol, and DHEA), markers of inflammation (hs-CRP and homocysteine), markers of insulin resistance (glucose, insulin, and HbA1c), vitamins (B12, vitamin D, and folate), and minerals (RBC magnesium, calcium, ferritin, and zinc). 

Results: The Prevalence of Abnormal Biomarkers 

Of the comprehensive panel analyzed, five biomarkers were significantly suboptimal. The study publication focused on their relevance to brain health and concussion, because the athletes were elite football players in a high-risk contact sport. The primary suboptimal biomarkers included omega-3 index (percent of fatty acids in red blood cell membranes that are omega-3s), AA:EPA ratio (ratio of inflammatory arachidonic acid to anti-inflammatory EPA), RBC magnesium, vitamin D, and homocysteine.  

Omega-3 Index (O3I)

The average O3I in this group was 4.66 percent with only one athlete above the recommended 8-percent standard reference value.3 The optimal reference range is considered 8-10 percent.4 In general, a low O3I is associated with lower cognitive flexibility, lower executive function, mood and personality issues, and altered brain function,5 in addition to cardiovascular-related health risks. 


This group’s average AA:EPA ratio of 29.13 was substantially higher than that of average American males (16.2) and the optimum level (<3).6 Linoleic acid contributes to increased AA:EPA and omega-6:omega-3 ratios. The study found linoleic acid was significantly lower in athletes drafted into the NFL versus those who were not drafted (p ≤0.05). In other research, linoleic acid and arachidonic acid were two of six metabolites that could be used to differentiate between patients with and without cognitive impairment following a TBI (higher levels of both fatty acids associated with more cognitive impairment).7 


Ninety percent of the participants showed an elevated homocysteine level (average of 11.4 µg/dL). The standard reference range is less than 11 µg/dL, and performance limits suggest less than 9 µg/dL.8

Homocysteine is an intermediate formed during methionine-to-cysteine metabolism and is directly dependent on vitamin B12, folate, betaine, or choline metabolism to remain normal; however, vitamin B12 and folate blood levels were normal in the study group. Previous studies show high blood levels of homocysteine can cause vascular endothelium injury, facilitates smooth muscle cell proliferation, and increases the risk of venous thrombosis.9 Also, elevated homocysteine is associated with brain atrophy, silent brain infarcts, and white matter hyperintensity. Such brain vascular changes can have particular relevance to athletes who compete in concussion-prone sports.  

Vitamin D

Vitamin D3 was below the standard reference range (<30 ng/mL) in 63 percent and below the research-backed optimal performance range (40-60 ng/mL)10 in 83.3 percent of athletes. The research shows adults who experience a TBI when they have a vitamin D deficiency have significantly lower Addenbrooke's Cognitive Examination scores, and that a vitamin D deficiency is also associated with more severe depressive symptoms.11 Vitamin D influences athletic performance through hundreds of processes – neurological function, cardiovascular health, glucose metabolism, bone health, and skeletal muscle performance (including strength and power).

RBC Magnesium

RBC magnesium levels were below the standard reference range (4.5–6.5 mg/dL) in 86 percent of athletes and below the loosely defined optimal performance reference range (5.5-6.5 mg/dL)12 in 90 percent of study participants (average = 4.1 mg/dL). Neuronal magnesium concentrations are of central importance in the regulation of N-methyl-d-aspartate (NMDA) receptor excitability. NMDA receptors are essential for neuronal plasticity, excitatory synaptic transmission, and excitotoxicity, playing an important role in plasticity, learning, and memory.13   

The Frequency of Abnormal Biomarker Results

Among the most compelling data are the frequency distributions of undesirable values found in this group. Just comparing the blood values to clinical ranges, no athlete presented with fewer than two abnormal biomarkers – 7 percent had two, 37 percent had three, 40 percent had four, and 17 percent had five abnormal values. In looking at optimal, rather than just standard ranges for athletes, a full 50 percent had five abnormal values.

What To Do If You Play a Contact Sport

Based on this study and the apparent prevalence of nutrient biomarker abnormalities in this population, it would be prudent to take steps to support athletes or others whose activities involve brain impact.

1. Test 

Comprehensive blood testing at least once a year, but better 2-3 times a year – pre-season, during the season, and post-season. WellnessFX has a Premium Panel that measures the significant biomarkers from this study for a baseline status. Thorne’s at-home tests can be used to monitor certain biomarkers, like vitamin D, between more comprehensive testing.

2. Optimize

The above-mentioned biomarkers can be modified through precise nutrition practices. Diet and supplementation play a crucial role in maintaining optimal nutritional status. Athletes should choose NSF Certified for Sport® supplements when possible:

  1. Low omega-3 index: Eat at least two servings of fatty fish a week. In addition, Thorne’s SuperEPA fish oil supplement promotes a healthy omega-3 index.* 
  2. Elevated AA: EPA ratio: Limit red meat and increase fatty fish and fish oil consumption.
  3. To support a healthy homocysteine level: Eat green leafy vegetables, beans, and animal protein, which provide the B vitamins folate, B2, B6, and B12 that are necessary for optimal homocysteine maintenance. Thorne’s B-Complex #6, which is NSF Certified for Sport, provides these B vitamins.* 
  4. Low RBC magnesium: Seeds and nuts are excellent sources of magnesium or consider Thorne’s Magnesium Bisglycinate powder, a perfect nighttime recovery powder to support increased magnesium blood levels, relax muscles, and promote a good night’s sleep.* The RDA for magnesium is 420 mg and one scoop provides 200 mg of highly absorbable magnesium.
  5. Low vitamin D: Dairy, eggs, mushrooms, fish, and sunshine can provide this crucial vitamin. Because there are limited dietary sources of vitamin D, taking a supplement can be a good option, particularly during the winter months of little or no sunshine or if your sport is indoors. Even in the case of outdoor sports like football, athletes wear clothing and sunblock, necessitating vitamin D supplementation in this population too.

3. Practice prophylactic nutritional support

An athlete involved in impact sports should be prepared for the unexpected. Thorne’s new SynaQuell powdered supplement provides nutritional support for individuals who experience frequent brain impacts.* The synergistic ingredients in SynaQuell support cellular energy production, are neuroprotective, balance inflammatory cytokines, and reduce oxidative stress.* Consider SynaQuell+ for post-impact brain support.* 


  1. Concussion in Athletes. [Accessed April 22, 2021]
  2. Daneshvar D, Nowinski C, McKee A, Cantu R. The epidemiology of sport-related concussion. Clin Sports Med 2011;30(1):1-17, vii.
  3. Harris W, Pottala J, Varvel S, et al. Erythrocyte omega-3 fatty acids increase and linoleic acid decreases with age: observations from 160,000 patients. Prostaglandins Leukot Essent Fatty Acids 2013;88(4):257-263.
  4. Johnston D, Deuster P, Harris W, et al. Red blood cell omega-3 fatty acid levels and neurocognitive performance in deployed U.S. service members. Nutr Neurosci 2013;16(1):30-38.
  5. Meyer B, Byrne M, Collier C, et al. Baseline omega-3 index correlates with aggressive and attention deficit disorder behaviours in adult prisoners. PLoS One 2015;10(3):e0120220.
  6. Holub B, Wlodek M, Rowe W, Piekarski J. Correlation of omega-3 levels in serum phospholipid from 2,053 human blood samples with key fatty acid ratios. Nutr J 2009;8:58.
  7. Yi L, Shi S, Wang Y, et al. Serum metabolic profiling reveals altered metabolic pathways in patients with post-traumatic cognitive impairments. Sci Rep 2016;6:21320.
  8. Lowering blood homocysteine with folic acid-based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists’ Collaboration. BMJ 1998;316(7135):894-898.
  9. Hao L, Chen L, Sai X, et al. Synergistic effects of elevated homocysteine level and abnormal blood lipids on the onset of stroke. Neural Regeneration Res 2013;8(31):2923-2931.
  10. Ogan D, Pritchett K. Vitamin D and the athlete: risks, recommendations, and benefits. Nutrients 2013;5(6):1856-1868.
  11. Jamall O, Feeney C, Zaw-Linn J, et al. Prevalence and correlates of vitamin D deficiency in adults after traumatic brain injury. Clin Endocrinol 2016;85(4):636-644.
  12. Malliaropoulos N, Tsitas K, Porfiriadou A, et al. Blood phosphorus and magnesium levels in 130 elite track and field athletes. Asian J Sports Med 2013;4(1):49-53.
  13. de Baaij J, Hoenderop J, Bindels R. Magnesium in man: implications for health and disease. Physiol Rev 2015;95(1):1-46.
  14. Kunces LJ, Keenan J, Schmidt CM, Schmidt MA. Molecular Deficits Relevant to Concussion Are Prevalent in Top-Ranked Football Players Entering the National Football League Draft. J Strength Cond Res. Published online September 16, 2021.