People take supplements to improve or optimize their health. So what happens when you look at the label, and the ingredient list is filled with unrecognizable additives?
The World Health Organization defines brain health as, “the state of brain functioning across cognitive, sensory, social-emotional, behavioral, and motor domains.” A healthy brain is a key component in achieving your full potential over your lifespan. A person might have a high-risk job or compete in a contact sport. Some individuals are born with genes that predispose them to adverse brain health issues. Others might be exposed to excessive environmental toxins, have had a brain trauma accident like a car crash or a fall, or live a stressful or unhealthy lifestyle. These factors increase the likelihood of suboptimal cognitive function now or down the road.
If you are concerned about brain health – no matter your current age – then you should periodically check several biomarkers that gauge your risk for brain-related health issues.
1. Omega-3 index
Although there can be more than 60 fatty acids in cell membranes, the total percentage of the two primary omega-3s – docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) – in red blood cell (RBC) membranes is used to calculate your omega-3 index (O3I). These two fatty acids play an integral structure-function role in cell health by maintaining cell structure. This facilitates optimal cellular function, like allowing nutrients to pass in and out of the cell and providing a layer of protection. A high O31 level is optimal because a low level is associated with multiple adverse health conditions, including cardiovascular disease and eye disease. Regarding the brain, studies show a higher O3I correlates with a larger total brain volume and hippocampal volume – the part of the brain responsible for learning and memory.1
Your O3I also has other implications. Research shows an inverse correlation between O3I and postpartum depression. Women with a low O31 during pregnancy tend to have the highest incidence and severity of depression in the first six months after giving birth.2 Research also shows a large percentage of athletes have a low O3I,3 which can impact muscle inflammation, immune function, and recovery after a brain injury.4
Doing an omega-3 index test can provide recommendations on how to optimize the omega-3 levels in your blood.
2. Phospholipid DHA
DHA, an omega-3 fatty acid concentrated in cell membrane phospholipids of the brain and nerves, represents up to 97 percent of the omega-3 fatty acids in the brain.5 In early life, a low DHA level is linked to poor neurological development and low IQ; and later in life, a low DHA level is related to cognitive dysfunction and an elevated risk for Alzheimer’s disease. In middle adulthood, research shows serum phospholipid DHA level is positively associated with better reasoning and memory, relating to improved cognitive performance.6
Athletes, the military, and individuals at risk for head injury are populations that should closely monitor this biomarker. Both a traumatic brain injury and repeated smaller brain injuries decrease DHA content in the brain, and a low DHA blood level worsens the injury response and recovery process.3
To support your DHA levels, consider a DHA-containing supplement. If you are pregnant, this can also support a healthy pregnancy, healthy fetal brain development and cognitive function throughout life.
3. BDNF
BDNF – brain-derived neurotrophic factor – is a protein released from neurons and is crucial for the growth and maintenance of brain and nerve cells. BDNF plays an important role in learning, memory, and behaviour, and has a broad influence on mood, sleep patterns, eating habits, and appetite.
Factors associated with having a low BDNF level include stress, aging, a sedentary lifestyle, smoking, air pollution, and eating a high-fat/high-sugar diet. A genetic mutation, seen in upward of 30 percent of certain ethnic groups, results in a lower BDNF level and differences in motor system function and learning compared to individuals without it.7
Exercise and healthy diet support BDNF levels. In addition, several nutrients commonly contained in nutritional supplements have been shown to increase BDNF, including whole coffee fruit extract,8 nicotinamide riboside and betaine.
4. RBC Magnesium
Magnesium is actively transported into the brain, where it plays an essential role in nerve transmission and neuromuscular conduction – the process by which the central nervous system controls muscle movement in the body. A higher magnesium level in the brain has been shown to promote communication between the neurons that enhance learning and memory.
Literature reviews show magnesium levels – blood, cerebrospinal fluid, and others – have an inverse relationship with migraines, depression, chronic pain, anxiety, and stroke.9 Similarly, in studies of individuals who have experienced a traumatic brain injury, magnesium levels tend to decrease following the insult, allowing a glutamate and calcium influx into the neurons that receive neurotransmitters, contributing to neuronal degradation and cell death.10 Many are at risk for a low magnesium level.
Because the body uses magnesium in so many processes and loses magnesium through sweat and urine, evaluating magnesium status can provide valuable information.
5. hs-CRP
High-sensitivity C-reactive protein (hs-CRP) is an inflammation marker often associated with heart disease risk, although there is strong evidence a high level is associated with inflammatory reactions throughout the body, including links to cerebrovascular and neurodegenerative diseases.11 Inflammation plays a role in the pathogenesis of common brain-related conditions, including general cognitive decline, which can progress to Alzheimer’s disease.
6. Vitamin D
Vitamin D levels are linked to many different body systems, including bone and muscle strength, immune function, and cognitive function. Age is a risk factor for a low vitamin D level, for reasons such as decreased synthesis in the skin and low dietary intake, and age is also associated with cognitive decline. Studies confirm associations with vitamin D deficiency and cognitive impairment, dementia, and various nervous system disorders.12 Athletes are at risk of being vitamin D deficient because of their increased needs.
7. Liver function biomarkers
Keeping the liver healthy is important for brain health because of its importance in detoxification, which affects the whole body. There is a liver-brain axis that involves bi-directional communication between the liver and the brain. Damaged bile ducts, liver inflammation, and liver injury can manifest as abnormal behaviour, compromised cognition, and changes in cerebral neurotransmission.13
8. Homocysteine
Homocysteine is an amino acid naturally produced during methionine-to-cysteine metabolism. Although it is a well-known risk factor for cardiovascular disease, elevated homocysteine is also associated with brain atrophy, silent brain infarcts, and white matter hyperintensity.14 Although everyone should aim to keep this value low, its known health effects make homocysteine of particular importance to individuals involved in activities with an increased risk for head injury or who have had a head injury in the past.
To be recycled to methionine, homocysteine requires a methyl donor from folate, vitamin B12, or betaine, or all three. Evaluating your homocysteine level, as well as measuring folate and vitamin B12, helps you understand how to optimize the level of each nutrient for efficient methylation.
Understanding the biomarkers associated with brain health and learning how to optimize them can minimize your risk for future health concerns and improve your healthspan.
- Satizabal CL, Himali JJ, Beiser AS, et al. Association of red blood cell omega-3 fatty acids with MRI markers and cognitive function in midlife: The Framingham Heart Study. Neurology 2022 Oct 5:10. doi: 10.1212/WNL.0000000000201296.
- Markhus MW, Skotheim S, Graff IE, et al. Low omega-3 index in pregnancy is a possible biological risk factor for postpartum depression. PLoS One 2013;8(7):e67617.
- Heileson JL, Anzalone AJ, Carbuhn AF, et al. The effect of omega-3 fatty acids on a biomarker of head trauma in NCAA football athletes: a multi-site, non-randomized study. J Int Soc Sports Nutr 2021;18(1):65.
- Thielecke F, Blannin A. Omega-3 fatty acids for sport performance – are they equally beneficial for athletes and amateurs? A narrative review. Nutrients 2020;12(12). doi:10.3390/nu12123712
- Greenberg JA, Bell SJ, Ausdal WV. Omega-3 fatty acid supplementation during pregnancy. Rev Obstet Gynecol 2008;1(4):162-169.
- Muldoon MF, Ryan CM, Sheu L, et al. Serum phospholipid docosahexaenonic acid is associated with cognitive functioning during middle adulthood. J Nutr 2010;140(4):848-853.
- McHughen SA, Rodriguez PF, Kleim JA, et al. BDNF val66met polymorphism influences motor system function in the human brain. Cereb Cortex 2010;20(5):1254-1262.
- Reyes-Izquierdo T. Argumedo R, Shu C, et al. Stimulatory effect of whole coffee fruit concentrate powder on plasma levels of total and exosomal brain-derived neurotrophic factor in healthy subjects: an acute within-subject clinical study. Food Nutr Sci 2013;4:984-990.
- Kirkland AE, Sarlo GL, Holton KF. The role of magnesium in neurological disorders. Nutrients 2018;10(6). doi:10.3390/nu10060730
- Institute of Medicine (US) Committee on Nutrition, Trauma, and the Brain. Erdman J, Oria M, Pillsbury L. Magnesium National Academies Press (US); 2011.
- Song IU, Chung SW, Kim YD, Maeng LS. Relationship between the hs-CRP as non-specific biomarker and Alzheimer’s disease according to aging process. Int J Med Sci 2015;12(8):613-617.
- Anjum I, Jaffery SS, Fayyaz M, et al. The role of vitamin D in brain health: A mini literature review. Cureus 2018;10(7):e2960.
- Chen J, Liu S, Wang C, et al. Associations of serum liver function markers with brain structure, function, and perfusion in healthy young adults. Front Neurol 2021;12:606094.
- 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.
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