Over the years there has been numerous articles and push by traditional and nontraditional medical specialists, concerning the utility or disparaging the consumption of minerals and vitamins. In fact, multivitamins are consumed by 31% of the population,[1] with Americans spending more than $30 billion on dietary supplements.[2] The Physician Health Study-II enrolled healthy male physicians age 50 and older and examined antioxidant-focused supplements (including 3.5 mg of manganese), revealing no benefit for all-cause mortality, cardiovascular death, or cancer outcomes.[3] In 2021, a report generated by Kaiser Permanente on behalf of the United States Preventative Task Force[4] did not reveal any clear evidence to support dietary supplements such as multivitamins (antioxidant-focused or broad-spectrum) and single dietary vitamins.

The study by Huang et al., titled “Association and pathways between dietary manganese intake and incident venous thromboembolism (VTE),”[5] explores the U.K. Biobank from 202,507 adults with dietary data collected from 24-hour diet questionnaires suggesting a possible association between low dietary manganese and incident VTE. This is in line with previous studies such at the Japan Collaborative Cohort study[6] and a small Italian case series,[7] which suggested low dietary manganese may be associated with VTE events. The trace mineral is found in a wide variety of foods, such as, shellfish, nuts, brown rice, oatmeal, legumes, and black tea, to name a few. Thus, deficiency is very rare, with no identified populations currently known to be at risk. There is a lack of many reports concerning toxicity of manganese from the diet, although a recent case report from a patient with a previous occupation as a welder presented to a clinic with neurological impairment confirmed by magnetic resonance imaging (MRI).[8] The patient was treated with intravenous ethylenediaminetetraacetic acid-based chelation, which abated the patient's symptoms and improved the MRI findings.

Manganese is essential to our bodies, acting as a natural enzymatic antioxidant that suppresses free radicals and peroxide. As stated by Huang et al,[5] it is a required component in the formation of manganese superoxide dismutase, which can reduce mitochondria oxidative stress.[9] In addition, manganese works with vitamin K to assist in wound healing. Both mechanisms may play an important role in the increased incidence of VTE events in patients with low blood levels of manganese ([Fig. 1]).

Although there is a lack of clinical benefit of vitamins in previous studies, it is important to note that all trials conducted were on healthy volunteers. Thus, it is wise to place into perspective that minerals and vitamins may be beneficial in individuals at dietary risk such as a deficiency of manganese. The authors add to the evidence of a potential association between manganese deficiency and VTE. Further studies are needed to increase the evidence of this association. In addition, further clinical trials exploring the benefit of multivitamins in patients with established cardiovascular disease is warranted.

Nevertheless, this epidemiological association needs to be put into context, in relation to the whole host of other associations with VTE. Some are well recognized and studied, for example, obesity,[10] family history,[11] pregnancy,[12] cancer, and kidney disease. Other interesting associations that have emerged, as reported in this journal, include sleep apnea,[13] assisted reproductive technology, and gender-affirming hormone therapy.[14] Of course, a particular risk factor does not occur in isolation, and often in clusters of multimorbidity, and the interactions between comorbidities and VTE may explain a substantial proportion of VTE mortality.[15] Put into this mix is now minerals and vitamins, but could these be simply related to other comorbidities associated with VTE? What a tangled web can be weaved linking VTE with various comorbidities and now as suggested by Huang et al,[5] minerals and vitamins.