Vitamin D and magnesium: wonder supplements?

I’m guessing you all know that I like my supplements. They provide a way for patients to positively change their health with a lower risk of adverse effects. However, as pharmacists, we must be aware of the limitations of the products in our aisles. That's why this column will be focusing on bite-sized (pun intended) reviews of supplementation and dietary interventions that can improve our patients' health. Vitamin D and COVID-19 Is there nothing that Vitamin D cannot improve? Well apparently Vitamin D is not very useful in reducing morbidity associated with SARS-CoV-2 infections.1 In this study, healthcare workers were given either high-dose or low-dose vitamin D to determine health outcomes of possible COVID-19 infections. The high dose was given 50,000IU/weekly for two weeks then 5000IU/daily and the “low” dose was given 2000IU/day. Treatment lasted for three months. Neither group showed a difference in COVID-19 infection morbidity. However, the high-dose group had only asymptomatic COVID-19 in 10 (26%) cases; while the low-dose group had twice as many COVID-19 cases, with mild clinical features in half of them. While this might not be exciting news, I did find a few interesting items in this study. These high doses were not associated with any reported adverse effects; serum calcium was within normal ranges in both groups. Vitamin deficiency was noted in 60% of all subjects and only 10% of subjects had normal vitamin D levels. Also, normal vitamin D levels (30 ng/mL or higher2) was achieved in only 53% of the subjects in the high-dose vitamin D group. Two takeaways here: Healthcare workers (so essentially us) might be deficient in Vitamin D and even 2000IU a day might not be suitable to correct this. L-TAMS magnesium and cognitive function Magnesium is another one of those supplements that seems to be good for everything. Recently, this supplement has been getting attention for its ability to help treat cognitive impairment in older adults.3 In a 12-week randomized, double-blind, placebo-controlled trial, magnesium l-threonate was given to patients with cognitive impairment. (These cognitive impairment concerns of memory and concentration were self-reported.) The trial used a proprietary supplement called Clarimem(R) containing L-TAMS (L-Threonic Acid Magnesium Salt). It is thought that this novel form of magnesium has greater uptake through the blood brain barrier. After the 12 weeks, subjects in the magnesium arm reported improved cognitive ability compared to placebo. While this sounds promising, there were a few interesting items of note within the study. Many of the cognitive tests (memory capacity and attention capacity) improved equally in the placebo group, so the difference did not reach significance. It was noted that training for these tests lead to cognitive improvements on their own. Also noted was that the magnesium group had reduced fluctuations in cognitive abilities over time. This means that cognitive abilities were consistently higher and that they experienced fewer “bad days.” Also, 30% of magnesium patients did not respond to treatment. Takeaways: magnesium can be helpful for cognitive function, but only certain forms can readily cross the blood brain barrier. For 30% of people, it just might not work. It also might reduce the number of “bad days,” cognitively speaking. Read: Well-researched: New book on healthy aging from pharmacist who banned homeopathics and sugar beverages. Magnesium supplementation can reduce inflammatory markers Keeping on the magnesium train, a meta-analysis of RCTs involving magnesium supplementation looked at human inflammatory markers.4 Seventeen RCTs were pooled (889 participants; mean age: 46 years; females: 62.5%). It was noted that magnesium supplementation reduced c-reactive protein levels and increased nitric oxide levels. Other inflammatory markers and antioxidant status were not affected. The salts used were citrate, oxide, chloride and pidolate. Magnesium pidolate is a new one for me also. Doses ranged between 250mg to 500mg, but most were over 300mg daily. The mechanism of action is not clear, however the researchers noted that Mg deficiency acts as a trigger for the inflammatory process. This lack of Mg leads to increased uptake of calcium in macrophages leaded to increased levels of cytokines.5 Takeaway: magnesium supplementation can reduce inflammatory markers such as CRP. But you should take over 300mg daily—it doesn’t matter which salt. Read: Clinical guidelines for treating psychiatric disorders with nutraceuticals and phytonutrients REFERENCES Karonova TL, Chernikova AT, Golovatyuk KA, Bykova ES, Grant WB, Kalinina OV, Grineva EN, Shlyakhto EV. Vitamin D Intake May Reduce SARS-CoV-2 Infection Morbidity in Health Care Workers. Nutrients. 2022 Jan 24;14(3):505. doi: 10.3390/nu14030505. PMID: 35276863; PMCID: PMC8839300. Michael F. Holick, Neil C. Binkley, Heike A. Bischoff-Ferrari, Catherine M. Gordon, David A. Hanley, Robert P. Heaney, M. Hassan Murad, Connie M. Weaver, Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 96, Issue 7, 1 July 2011, Pages 1911–1930, https://doi.org/10.1210/jc.2011-0385 Liu G, Weinger JG, Lu ZL, Xue F, Sadeghpour S. Efficacy and Safety of MMFS-01, a Synapse Density Enhancer, for Treating Cognitive Impairment in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial. J Alzheimers Dis. 2016;49(4):971-990. doi:10.3233/JAD-150538 Veronese N, Pizzol D, Smith L, Dominguez LJ, Barbagallo M. Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials. Nutrients. 2022;14(3):679. Published 2022 Feb 5. doi:10.3390/nu14030679 Maier JA, Castiglioni S, Locatelli L, Zocchi M, Mazur A. Magnesium and inflammation: Advances and perspectives. Semin Cell Dev Biol. 2021 Jul;115:37-44. doi: 10.1016/j.semcdb.2020.11.002. Epub 2020 Nov 18. PMID: 33221129.

Vitamin D and magnesium: wonder supplements?

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Ian Lloyd