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Pneumonia is a major public health problem for older adults, being one of the leading causes of hospitalization and death, particularly for elderly nursing home residents. We previously conducted a clinical trial in which we demonstrated that 29% of nursing home residents had low serum zinc levels coinciding with a two-fold increase in pneumonia incidence and duration in comparison to individuals with adequate serum zinc levels. However, causality could not be inferred and necessitates a double-blind clinical trial. To determine the appropriate supplementation dose for such a trial we are conducting a randomized, placebo-controlled, double-blind clinical pilot trial aimed at delineating the optimal dosage (30 and 60 mg/day elemental Zn) and establishing safety. The results from the pilot study will be leveraged to inform our larger randomized clinical trial designed to study the effect of zinc supplementation in nursing home elderly with low serum zinc levels on respiratory infections, antibiotic use, and duration of sick days with pneumonia. In tandem with dose optimization, we will evaluate the correlation between serum zinc and pan-T cell zinc levels, given that T cells and their zinc levels are important in the response and resolution of respiratory infections but whose correlation has only been extrapolated and not demonstrated. Herein we present the study rationale and protocol, as well as discuss specific challenges we encountered in securing a manufacturer for the study agents and when recruiting from nursing home populations during the COVID-19 pandemic. In light of these experiences, we provide recommendations for future clinical trials under circumstances where supply chains are disrupted, and recruitment pools are constrained or unavailable.Clinical trial registrationhttps://clinicaltrials.gov/, NCT05527899.

ObjectiveEpidemiological studies suggest that consumption of fruits and vegetables (FV) is negatively associated with the incidence of certain cancers and mortality. However, a causal relationship has not been demonstrated. Thus, we investigated the effect of life-long consumption of high level of FV on median lifespan, key biological functions, and pathologies in mice fed low-fat (LF) or high-fat (HF) diets and the underlying mechanisms.MethodsUsing a 2 × 2 factorial design, 5 weeks-old male C57BL/6J mice were randomly assigned to one of four groups (n = 60/group): LF (LF-C, 10% kcal fat), HF (HF-C, 45% kcal fat) or each supplemented with 15% (w/w) of a unique FV mixture (LF + FV and HF + FV, respectively). Mice were euthanized when one group reached 50% mortality. Body weight and composition, tumor incidence, and death were monitored. Blood levels of lipids and pro-inflammatory cytokines were assessed.ResultsAfter 21 months of feeding, HF-C group reached 50% mortality, at which time mice in all groups were terminated. HF-C had higher mortality (50.0%) compared to the LF-C group (18.3%, p = 0.0008). Notably, HF-FV had lower mortality (23.3%) compared to HF-C group (p = 0.008); there was no significant difference in mortality between HF-FV and LF-C groups. Tumors were found in all groups, and were predominantly present in the liver, followed by those of lung, intestine, and seminal vesicle. Tumor incidence in the HF-C group (73.3%) was higher than that in LF-C group (30.0%, p

IntroductionThe safety of novel forms of iron in healthy, iron-replete adults as might occur if used in population-based iron supplementation programs was examined. We tested the hypotheses that supplementation with nanoparticulate iron hydroxide adipate tartrate (IHAT), an iron-enriched Aspergillus oryzae product (ASP), or ferrous sulphate heptahydrate (FS) are safe as indicated by erythrocyte susceptibility to malarial infection, bacterial proliferation, and gut inflammation. Responses to FS administered daily or weekly, and with or without other micronutrients were compared.MethodsTwo phases of randomized, double-blinded trials were conducted in Boston, MA. Phase I randomized 160 volunteers to six treatments: placebo, IHAT, ASP, FS, and FS plus a micronutrient powder (MNP) administrated daily at 60 mg Fe/day; and FS administered as a single weekly dose of 420 mg Fe. Phase II randomized 86 volunteers to IHAT, ASP, or FS administered at 120 mg Fe/day. Completing these phases were 151 and 77 participants, respectively. The study was powered to detect effects on primary endpoints: susceptibility of participant erythrocytes to infection by Plasmodium falciparum, the proliferation potential of selected pathogenic bacteria in sera, and markers of gut inflammation. Secondary endpoints for which the study was not powered included indicators of iron status and gastrointestinal symptoms.ResultsSupplementation with any form of iron did not affect any primary endpoint. Regarding secondary endpoints, in Phase I participants taking IHAT more frequently reported abdominal pain (27%, p = 0.008) than other iron forms; those taking the weekly FS dose more frequently reported nausea (20%, p = 0.009) than the other forms and modes of administration. In phase II, no such differences were observed.DiscussionWith respect to the primary endpoints, few differences were found when comparing these forms of iron, indicating that 28 days of 60 or 120 mg/day of IHAT, ASP, or FS may be safe for healthy, iron-replete adults. With respect to other endpoints, subjects receiving IHAT more frequently reported abdominal pain and nausea, suggesting the need for further study.Clinical Trial RegistrationClinicalTrials.gov, NCT03212677; registered: 11 July 2017.