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For decades, deficiencies in micronutrients such as magnesium and vitamin D have been linked to conditions such as depression and obesity, as well as their associated hallmarks of systemic inflammation. These observations raise questions about whether certain nutritional inadequacies might play a causal role in these conditions and whether supplementation may help regulate symptom severity. Now, a recent randomized double-blind placebo-controlled clinical trial reveals that co-supplementation with magnesium and vitamin D significantly decreases depression scores and body weight in healthy women with obesity.

The study recruited 102 women with obesity (body mass index, 30–40; ages, 20-45 years) with mild-to-moderate depression and no indication of other health issues such as hormonal dysfunction, autoimmune disease, or diabetes. The study investigators randomly allocated the women to one of four groups to receive varying combinations of a weekly soft gel containing 50,000 international units (IU) of vitamin D, a daily tablet of 250 milligrams magnesium, and/or a placebo. The groups comprised:

1) Co-supplementation: weekly vitamin D + daily magnesium

2) Vitamin D only: weekly vitamin D + daily magnesium placebo

3) Magnesium only: daily magnesium + weekly vitamin D placebo

4) Control: weekly vitamin D placebo + daily magnesium placebo

The investigators collected participants’ blood samples at baseline and following eight weeks of supplementation. The samples revealed that while the women on average had adequate baseline serum levels of magnesium and borderline-adequate levels of vitamin D, their health outcomes and biomarkers nonetheless showed the greatest improvements as a result of co-supplementation with both micronutrients. For instance, women who received both magnesium and vitamin D lost more weight over the duration of the intervention compared to all the other groups, in the absence of any observed changes in their dietary patterns. They also showed the greatest average reduction in depression scores over time, although all participants (including controls) exhibited some degree of symptom relief after the eight-week intervention - an observation the researchers attributed in part to the placebo effect.

The women’s blood samples revealed a similar picture, with co-supplementation outperforming all other conditions (although individual supplementation with either vitamin D or magnesium still yielded significant improvements over controls). For instance, combining magnesium and vitamin D achieved the greatest reduction in plasma levels of pro-inflammatory tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and interleukin 6 (IL-6). It also generated the highest boost in brain-derived neurotrophic factor (BDNF) and sirtuin-1 (SIRT1) – a protein widely known for its involvement in regulating autophagy and longevity-promoting genes.

These findings reveal that co-supplementation with a weekly 50,000 IU dose of vitamin D and a daily 250 mg of magnesium can aid weight loss, enhance mood, and improve a host of blood biomarkers pertaining to systemic inflammation, brain functioning, and longevity. Moreover, the fact that positive health outcomes can be observed despite an absence of marked micronutrient deficiencies raises the possibility that current medical guidelines on adequate ranges of plasma levels and RDAs for vitamin D and magnesium, respectively, may be insufficiently high for optimal health outcomes.

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