Tier 3 — preclinical

Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly

Urban Alehagen, Jan Aaseth, Jan Alexander, Peter Johansson
PLOS ONE 2018 13(4):e0193120

Bibliography

PubMed
PMID 29641571
PubMed Central
PMC5894963
DOI
10.1371/journal.pone.0193120
Trial registry
View on ClinicalTrials.gov Registered trial — results not yet published in a peer-reviewed journal.
Funding
Part of the analysis costs was supported by Pharma Nord A/S, the County Council of Östergötland and Linköping University. The funding organizations were reported to have no role in design, management, analysis, interpretation or manuscript preparation.
Competing interests
The publication disclosed that the work was partially supported by Pharma Nord through trial tablets/capsules; the authors reported no patents or products in development and stated this did not alter adherence to PLOS policies.

Study snapshot

DesignTwelve-year mortality follow-up of a prospective randomized double-blind placebo-controlled four-year intervention; intention-to-treat analyses based on original assignment.
ModelOriginal community-dwelling older Swedish KiSel-10 cohort.
Sample443 original randomized participants: 221 active combination and 222 placebo; no participant lost to mortality follow-up.
InterventionOriginal four-year Bio-Quinon CoQ10 200 mg/day + SelenoPrecise selenium 200 µg/day versus placebo; supplementation ended at 48 months.
DurationFour-year intervention with cardiovascular mortality follow-up to a median about 12 years.
EndpointsCardiovascular mortality at 12 years; Univariate and multivariable Cox hazard ratios; Subgroups: ischemic heart disease, diabetes, hypertension, NYHA III

What the study showed, in plain terms

This paper extended mortality follow-up of the same KiSel-10 cohort to about 12 years. The original supplements had been stopped after four years; subsequent years were follow-up based on original randomized assignment.

Cardiovascular mortality was 62/221 (28.1%) in the original selenium+CoQ10 group versus 86/222 (38.7%) in placebo (p<0.0001). The univariate HR was 0.58 (95% CI 0.42–0.79; p<0.0007) and the multivariable HR was 0.59 (95% CI 0.42–0.81; p=0.001).

Subgroup hazard ratios also favored original active assignment in participants with ischemic heart disease (HR 0.52), diabetes (0.50), hypertension (0.60) and NYHA class III limitation (0.49). These findings remain hypothesis-generating because they derive from a small single-cohort combination intervention and cannot identify whether selenium, CoQ10, their interaction or other factors explain the effect.

Key findings

  • 12-year CV mortality: 62/221 (28.1%) active vs 86/222 (38.7%) placebo; p<0.0001.
  • Univariate HR 0.58 (95% CI 0.42–0.79; p<0.0007).
  • Multivariable HR 0.59 (95% CI 0.42–0.81; p=0.001).
  • IHD subgroup HR 0.52 (95% CI 0.30–0.90; p=0.02); diabetes HR 0.50 (95% CI 0.27–0.93; p=0.03); hypertension HR 0.60 (95% CI 0.41–0.85; p=0.005); NYHA III HR 0.49 (95% CI 0.27–0.88; p=0.002).
  • Only 228 completed the original 48-month intervention; 86 died and 129 withdrew, although mortality follow-up thereafter was complete via national records.

What this study can and cannot tell us

  • This is the same KiSel-10 cohort, not a new randomized replication.
  • Combination intervention means no CoQ10-specific mortality effect can be estimated.
  • Small, geographically restricted, older, low-selenium population; authors explicitly characterize results as hypothesis-generating.
  • Subgroup analyses increase multiplicity and should be treated as exploratory.
  • Most of the 12-year interval occurred after trial supplementation stopped, so mechanism of persistent separation is uncertain.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology