Today I am excited to present an interesting and relevant topic to most of us living in an industrialized country – micronutrient deficiencies! Micronutrients include essential vitamins and minerals and today I will focus on two — magnesium and selenium — that are becoming increasingly scarce in our diet due to soil depletion and decreased diet diversity. Scroll to learn more!
I made a graphic below for those of us that are more visual learners (including myself) and I will also talk about some of the data I uncovered while researching this topic.
The Problem: Climate Change and Micronutrient Deficiencies
One paper that I read went into the effects of climate change over the next 50 years and how it will impact selenium levels. Agriculture and soil composition are definitely not my areas of expertise and I did my best to tease out the high points. Basically, in the coming years high precipitation and aridity (dryness) will negatively affect soil selenium (Se) concentrations by causing removal of moisture from the soil column (which will reduced Se mass transport through the soil).
Further, increased climate temperature will alter soil organic carbon content and decrease Se concentrations.7 These temperature changes will also alter the pH of the topsoil which will decrease Se levels (see the figure below). From an agricultural standpoint, failure to rotate crops and utilizing the same acreage year after year for the same crops will deplete the soil of vital nutrients and further deplete the top soil.
What does this mean exactly? Less Se will be absorbed by plants (less uptake) meaning less content in the plants we eat and those of the animals we eat (after all, the micronutrient content of meats that we eat depend on the feed they are given).8
Side Effects of Selenium Deficiency:
As shown in the graphic above, side effects of Se deficiency may include poor metabolism, increased cancer risk (due to decreased scavenging of free radicals), poor wound healing, and increased risk of viral infection.4,6,8,10,11
This is an image from one of my medical school lectures first year and it has stuck in my mind ever since. the D1 and D2 stand for 5′-deiodinases type 1 and 2 — these enzymes are selenoproteins (i.e. depend on Se to function properly). What the image above is demonstrating is that D1 and D2 are critical enzymes for converting T4 thyroid hormone into T3 which is the active form in the body that goes on to all the organs listed on the right to exert important metabolic effects. Thus, without selenium metabolism may suffer.
Further, glutathione is one of the most abundant antioxidants in our bodies (we actually produce glutathione, whereas most other antioxidants are consumed by us in the form of leafy greens, fruits, etc.). As you can see in the figure above Reduced Glutathione becomes Oxidized Glutathione when scavenging free radicals (i.e. there are many free radicals in our environment, examples include excess sunlight, pollution and exposure to toxins like cigarette smoke) and this process is dependent on selenium.
Other possible mechanisms of Se include DNA stability and influencing necrosis and apoptosis of malignant cells. Studies have demonstrated that higher Se levels correlate with decreased cancer risk, likely in part because of these mechanisms and being able to attenuate free radical damage. Free radicals cause damage to our DNA and when this DNA damage is improperly repaired it can increase risk for cells going “rogue” and cancer developing (please bear in mind this explanation has been greatly simplified; if you are interested in reading further, check out this article).
Lastly, I would like to touch on the anti-viral effects of Se. One study by Moghaddam et al. collected serum samples from 33 COVID-19 patients and compared to European reference data. Se status was less than the <2.5%ile in ~40% of COVID samples. Further, the researchers found that Se status was significantly higher in COVID patients surviving compared to non-survivors (Se: 53.3+/- 16.2 vs. 40.8+/-8.1 mcg/L).11 It is important to clarify that correlation does NOT equal causation, however this data is interesting in supporting the anti-viral effects of Se.
What about Magnesium?
Magnesium (Mg) is the second most abundant intracellular cation and is important for numerous bodily functions. Symptoms of low Mg levels vary widely and may include abnormalities listed below:
One of the problems of identifying Magnesium deficiency is that it can be present without serum hypomagnesemia. Normally, we test serum levels of Mg by taking a blood sample with frank deficiency <1.5 mg/dL and subclinical < 1.8 mg/dL. The problem with this is that serum magnesium is tightly regulated and represents <1% of Mg in the body (3). In reality, we should be looking at ionized magnesium which is biologically active. Ionized magnesium (iMg) constitutes 50% of the total magnesium in the blood and represents the electrophysiologically active portion. 10% of magnesium in the blood is complexed with anions, and the remaining 30–40% is bound to albumin.6 However, measuring ionized magnesium requires a test separate from measuring blood levels and thus is not routinely done in hospitals.
Roles of Magnesium:
In one study, Scanlan et al. (4) fed rats a Mg deficient diet and showed intestinal inflammation after 3 weeks. The study further demonstrated increased sensitivity to intestinal ischemia (normally non-injurious amount of time of 10 min) and amplification of neutrophilic infiltration (Neutrophil/PMN infiltration and mucosal injury are classic features of oxidative stress induced by mesenteric ischemia and subsequent reperfusion).4
Further, Scarpati et al.6 discuss that cardiovascular dysfunction and systemic inflammatory response syndrome in ICU patients are closely related to hypomagnesemia including a higher mortality rate and longer ventilatory support.
Unfortunately, less than half of US adults do not meet estimated average requirement of magnesium intake.9 Alcohol consumption, diuretic use, proton pump inhibitor (i.e. acid reducer) and kidney disease diminish magnesium reabsorption capacity. These risk factors are widely prevalent among our aging population and thus we may continue to see hypomagnesemia among patients.
Further, Mg plays a critical role in synthesis and metabolism of PTH and vitamin D and thus is critical for bone health.5
Lastly, intracellular Mg plays a key role in regulating insulin, insulin-mediated glucose uptake and vascular tone and low levels have been associated with higher rates of Type 2 Diabetes. One of the proposed mechanisms is that lower levels of Mg leads to defective tyrosine kinase activity and impairment in insulin action (tyrosine kinase receptors can be thought of as the lock on a door – insulin acts as the key by binding to TK receptors and thus allowing glucose to enter the cell; thus impaired TK activity is correlated with worsening of insulin resistance and higher blood glucose levels.1
What can be done about it?
I would like to highlight this part of my graphic. I am a big proponent of getting all the vitamins and minerals we need through our diet. By far the greatest source of selenium in the diet is through brazil nuts – just 2-3 brazil nuts per month can ensure you have enough of this mineral. Additionally, brazil nuts can lower LDL (“bad”) cholesterol. Other Se sources include fortified products, seafood, and animal protein.
Magnesium can be found in leafy and cruciferous veggies (think spinach, kale, brussels sprouts) as well as dark chocolate (mmm!).
However as mentioned above with the risk of soil depletion and increased risk factors that impair absorption (e.g. rising rates of chronic kidney disease) this may not be a possibility for folks. Magnesium supplementation can be confusing. I recommend starting with a supplement like magnesium bisglycinate or malate which are better absorbed and thus will not cause digestive troubles. Magnesium citrate can also be helpful if struggling with constipation. I like the Natural Vitality Calm brand – it’s a powder that I scoop into warm water about an hour before bed and helps relax muscles and makes me sleepy for bed. Lastly, Magnesium L-threonate is a special formulation of Mg that can cross the blood-brain barrier and may also help promote restful sleep and improved relaxation.
For selenium repletion, I would recommend starting on the lower end (<100 micrograms per day) as Se has a narrow therapeutic index meaning over supplementation can easily lead to toxicity (high build-up of the mineral in the blood). For this reason, whenever starting a new vitamin or herb supplement, always discuss with your doctor to make sure it is safe to do so.
That is all for today. Questions, comments? Please post below!
References:
- Barbagallo M, Dominguez LJ. Magnesium and type 2 diabetes. World J Diabetes. 2015 Aug 25;6(10):1152-7. doi: 10.4239/wjd.v6.i10.1152. PMID: 26322160; PMCID: PMC4549665.
- Lei Fan, Xiangzhu Zhu, Andrea Rosanoff, Rebecca B Costello, Chang Yu, Reid Ness, Douglas L Seidner, Harvey J Murff, Christianne L Roumie, Martha J Shrubsole, Qi Dai, Magnesium Depletion Score (MDS) Predicts Risk of Systemic Inflammation and Cardiovascular Mortality among US Adults, The Journal of Nutrition, Volume 151, Issue 8, August 2021, Pages 2226–2235, https://doi.org/10.1093/jn/nxab138
- Hruby, Adela PhD, MPH; McKeown, Nicola M. PhD. Magnesium Deficiency: What Is Our Status?. Nutrition Today: 5/6 2016 – Volume 51 – Issue 3 – p 121-128 doi: 10.1097/NT.0000000000000158
- Scanlan, B. J., Tuft, B., Elfrey, J. E., Smith, A., Zhao, A., Morimoto, M., … & Shea-Donohue, T. (2007). Intestinal inflammation caused by magnesium deficiency alters basal and oxidative stress-induced intestinal function. Molecular and cellular biochemistry, 306(1), 59-69.
- Deng, X., Song, Y., Manson, J. E., Signorello, L. B., Zhang, S. M., Shrubsole, M. J., … & Dai, Q. (2013). Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III. BMC medicine, 11(1), 1-14.
- Scarpati G, Baldassarre D, Oliva F, Pascale G, Piazza O. Ionized or Total Magnesium levels, what should we measure in critical ill patients?. Transl Med UniSa. 2020;23:68-76. Published 2020 Oct 1. doi:10.37825/2239-9747.1015
- Jones, G. D., Droz, B., Greve, P., Gottschalk, P., Poffet, D., McGrath, S. P., … & Winkel, L. H. (2017). Selenium deficiency risk predicted to increase under future climate change. Proceedings of the National Academy of Sciences, 114(11), 2848-2853.
- Reis, A. R. D., El-Ramady, H., Santos, E. F., Gratão, P. L., & Schomburg, L. (2017). Overview of selenium deficiency and toxicity worldwide: affected areas, selenium-related health issues, and case studies. In Selenium in plants (pp. 209-230). Springer, Cham.
- Fan, L., Zhu, X., Rosanoff, A., Costello, R. B., Yu, C., Ness, R., … & Dai, Q. (2021). Magnesium Depletion Score (MDS) predicts risk of systemic inflammation and cardiovascular mortality among US adults. The Journal of nutrition, 151(8), 2226-2235.
- Hariharan, S., & Dharmaraj, S. (2020). Selenium and selenoproteins: It’s role in regulation of inflammation. Inflammopharmacology, 28(3), 667-695.
- Moghaddam, A., Heller, R. A., Sun, Q., Seelig, J., Cherkezov, A., Seibert, L., … & Schomburg, L. (2020). Selenium deficiency is associated with mortality risk from COVID-19. Nutrients, 12(7), 2098.