Selenium and CoQ10 supplementation and their effect on D-dimer

Relation

Alehagen U, Aaseth J, Lindahl TL, Larsson A, Alexander J. Dietary supplementation with selenium and coenzyme Q10 prevents increases in plasma D-dimer while reducing cardiovascular mortality in an older Swedish population.Nutrients. 2021;13(4):1344.

Study objective

To determine the effect of selenium and CoQ10 supplementation on D-dimer and cardiovascular mortality in an older Swedish population

Draft

Randomized, double-blind, placebo-controlled trial

Participant

Investigators examined 876 volunteers, of whom 443 were evaluated for consideration in the study. Of these, 213 participants met the criteria and were included in the study; 106 participants received the active combined supplement and 107 received the control placebo. The participants were between 70 and 88 years old. Investigators did not disclose the gender distribution in the published article. The participants were Swedish and Caucasian.

Inclusion criteria were:

• Alter ≥70 Jahre.
• Obwohl dies kein spezifisches Einschlusskriterium war, hatten alle Teilnehmer niedrige Selenspiegel im Serum (durchschnittlich 67 µg/L, was ungefähr einer Aufnahme von 35 µg pro Tag entspricht).
• Die Teilnehmer wurden nur aus einer ländlichen Gegend in Schweden rekrutiert.

Exclusion criteria were:

• Unfähig, regelmäßig (alle 6 Monate) zur Phlebotomie und Beurteilung zum Gesundheitszentrum zu reisen.
• Erkrankungen, von denen bekannt ist, dass sie das D-Dimer beeinflussen, einschließlich Vorhofflimmern, Behandlung mit Antikoagulanzien, bösartige Erkrankungen und vergrößerter linker Vorhof (größer als 40 mm).

Additional exclusion factors included recent myocardial infarction within the last month, planned cardiovascular surgery or procedure in the next 4 weeks, concerns about awareness or consent, serious illness that would make 4-year survival unlikely, and alcohol/drug abuse.

Study parameters assessed

Participants received either 100 mg of coenzyme Q10 (ubiquinone) twice daily and 100 mcg of selenium yeast twice daily or placebo for 48 months.

Primary outcome measures

D-dimer levels and cardiovascular mortality were the primary endpoints of the study.

Key insights

The investigators reported 2 important key findings. The first was that participants supplemented with CoQ10 and selenium yeast did not experience the same increase in D-dimer as those in the placebo group (P=0.006). Second, those with baseline D-dimer levels above the median in the supplementation group had significantly lower cardiovascular mortality (P=0.014).

Practice implications

This study asked a number of very specific questions, making extrapolation to other populations or typical practices relatively difficult. The population was older, aged more than 70 years. The study recruited from an area in Sweden with low soil selenium levels, and the participants actually had low serum selenium levels. D-dimer did not increase during the study period, therefore the study primarily reports prevention of an expected increase in D-dimer. Regarding reduced cardiovascular risk, this endpoint was only observed in patients with elevated D-dimer levels at baseline. The duration of the study is long enough for some mortality information to be relevant, but the sample size is rather small, which may introduce uncertainty in the results. Because all participants are Caucasian, it is difficult to know whether patients of other ethnicities would receive the same benefit.

Real-world replication, based solely on the published study, would suggest that coenzyme Q10 as ubiquinone 100 mg twice daily along with selenium as selenium yeast 100 mcg twice daily for up to 4 years in elderly Caucasian patients with low serum selenium levels, at least slightly elevated D-dimer levels, and none of the participant exclusion factors such as Atrial fibrillation, anticoagulant use, known malignancy, and enlarged left atrium greater than 40 mm. Outside these parameters, the benefit of the intervention should be extrapolated with caution.

While this is a very specific practice takeaway in the context of the study, clinicians can review some other practice implications that are not directly related to the primary endpoints.

D-dimer is probably known for its role in the diagnosis of venous thromboembolism and the exclusion of pulmonary embolism.¹However, D-dimer can also be used to evaluate peripheral arterial disease activity because D-dimer represents the breakdown of fibrin.²Doctors should also recognize that D-dimer increases after age 50.³It can also be used as a marker of inflammation without thromboembolism.⁴Another interesting point is that D-dimer may have prognostic value in Covid-19.⁵D-dimer may be underutilized in the evaluation of patients at risk for cardiovascular disease and atherosclerosis.⁵It may also be one of the best markers of endothelial function.⁶Since there is only a weak correlation between C-reactive protein (CRP) and D-dimer,⁷Clinicians should not rely solely on the former to determine systemic inflammation, particularly that of cardiovascular origin. The bottom line is that clinicians should not forget about D-dimer or relegate it only to embolic events.

The bottom line is that clinicians should not forget about D-dimer or relegate it only to embolic events.

Clinicians can speculate as to why researchers chose this combination of CoQ10 and selenium. First, there are previous studies available. The same research group published on CoQ10 and selenium on other inflammatory markers, including sP-selectin, CRP, osteopontin, osteoprotegerin and soluble tumor necrosis factor receptors 1 and 2.^8.9Other than CRP, these are not common, relevant markers for most clinicians. Von Willebrand factor and plasminogen activator inhibitor-1 were also endpoints in studies using the combination of coenzyme Q10 and selenium.¹⁰Another study examined the combination in patients who suffered a myocardial infarction.¹¹

Previous human studies are certainly a good starting point for future studies, but is there any biochemical relevance? Interestingly, there are very good reasons for this combination from a biochemical perspective. Many clinicians are familiar with the two most common commercially available versions of CoQ10, ubiquinone and ubiquinol, the latter often referred to as the active or reduced form. Ubiquinone is converted into ubiquinol in cells. In the cytosol of cells, there is a selenoenzyme called thioreductase1 that supports this conversion. It should be noted that this study used selenium yeast as a supplemented form and not other common forms of selenium, such as selenomethionine or selenium selenite. It is unclear whether forms of selenium other than selenium yeast would be equally useful in this population. In other populations it has been speculated that the form of selenium is quite important.¹²The different forms of selenium have different physiological effects, as demonstrated by an in vivo study evaluating this variation.¹³

For people with sufficient selenium levels, it is not clear whether supplementation is necessary or useful. It is believed that optimal cellular function requires 75 mcg of selenium per day;¹⁴However, for optimal expression of selenoproteins, intake levels of 100 to 150 µg per day may be required.^fifteenIf there is increased oxidative stress or inflammatory diseases, this amount can be adjusted upwards.¹⁶Selenium concentrations in the serum that are considered sufficient are above 100 µg/l. Northern European countries such as Sweden, where this study was conducted, are thought to have low soil selenium levels, which may contribute to low dietary intake and low serum levels and an association with higher cardiovascular mortality.¹⁷

In the absence of the very specific population of this study, clinicians could see broader relevance of D-dimer as a marker of inflammation and endothelial function, a better understanding of CoQ10 forms as well as selection of selenium forms and consideration of serum concentrations of selenium for optimal function.

From a clinical perspective, the dosage of CoQ10 and selenium yeast appears to be quite safe and not excessive. And while positive benefits may not necessarily be extrapolated to extrapolated populations, it seems reasonable to evaluate or supplement with selenium when insufficiency is possible or likely, particularly in those over 50 years of age or those with mildly elevated D-dimer. The dosage of 200 mg of Coenzyme Q10 per day also often appears to be prudent due to its use in most tissues of the body.