Background/Objectives: Youthful, smooth skin is highly desired in modern society. Individuals invest in cosmetics, plastic surgeons, and dermatologists in pursuit of perfect skin. However, many do not seek out dietary changes to improve skin health. Although research has been conducted on the role of nutrition and select nutrients and phytonutrients on skin health, there is a lack of healthy food recommendations for clear skin. Methods: The literature was assessed to determine which nutrients and phytonutrients play a significant role in the protection and maintenance of skin health. Key compounds were highlighted as there is evidence to suggest they have a significant role in skin health: vitamin A, vitamin C, vitamin D, vitamin E, zinc, omega-6 and omega-3 fatty acids, polyphenols/flavonoids, copper, selenium, and silicon. USDA FoodData Central and FooDB (food database), were utilized to select foods and food groups containing the key nutrients and phytonutrients. Results: A skin-healthy dietary pattern is proposed in addition to a scoring system to assess diet. A sample skin-healthy daily diet was designed, using only whole foods, that met the Daily Values for vitamins and minerals and contained key compounds for skin health. Conclusions: There is a clear link between nutrition and skin health, or nutritional dermatology; however, more research needs to be done to find the intersection between both disciplines.

Over the millennia, patterns of food consumption have changed; however, foods were always whole foods. Ultra-processed foods (UPFs) have been a very recent development and have become the primary food source for many people. The purpose of this review is to propose the hypothesis that, forsaking the evolutionary dietary environment, and its complex milieu of compounds resulting in an extensive metabolome, contributes to chronic disease in modern humans. This evolutionary metabolome may have contributed to the success of early hominins. This hypothesis is based on the following assumptions: (1) whole foods promote health, (2) essential nutrients cannot explain all the benefits of whole foods, (3) UPFs are much lower in phytonutrients and other compounds compared to whole foods, and (4) evolutionary diets contributed to a more diverse metabolome. Evidence will be presented to support this hypothesis. Nutrition is a matter of systems biology, and investigating the evolutionary metabolome, as compared to the metabolome of modern humans, will help elucidate the hidden connections between diet and health. The effect of the diet on the metabolome may also help shape future dietary guidelines, and help define healthy foods.

Background: Polypharmacy, commonly defined as the use of five or more medications, is highly prevalent among elderly patients with heart failure. While guideline-directed therapy improves survival, excessive or inappropriate medication use may increase mortality, hospitalization, and treatment burden. Aim: This study aimed to evaluate the association between polypharmacy and clinical outcomes in elderly patients with heart failure, including mortality, hospitalization, and quality of life. Methods: We conducted a systematic literature search in PubMed, Cochrane, and Scopus to identify observational studies assessing the impact of polypharmacy (defined as ≥5 medications) on elderly patients (≥65 years) with heart failure. Search strategies combined keywords (e.g., "heart failure", "polypharmacy") and subject headings (e.g., MeSH). The initial search yielded a total of 1,082 records. Studies were excluded if they were narrative reviews, case reports, or did not report quantitative outcomes of interest, such as mortality or hospitalization rates. After removing duplicates, titles and abstracts were screened based on predefined inclusion criteria. Following a full-text review of potentially eligible articles, 38 studies were included in the final systematic review, representing a pooled population of >250,000 participants. Of these, 11 studies provided sufficient quantitative data as Hazard Ratios with 95% Confidence Intervals and were included in the final meta-analysis for mortality and hospitalization. Findings from the remaining studies were synthesized narratively. Two reviewers independently screened, extracted data, and assessed study quality. A random-effects model was used to pool hazard ratios (HRs) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I2 statistic. Subgroup analyses were performed by medication type (heart failure–specific vs. non-cardiovascular), setting (community vs. hospital), and frailty status. Results: Polypharmacy was present in >70% of elderly patients with heart failure, with hyper-polypharmacy affecting 20–30%. Our pooled analysis, visualized in the accompanying forest plot (Figure 1), demonstrated increased all-cause mortality with polypharmacy (HR 1.38, 95% CI 1.25–1.60) and greater risk with hyper-polypharmacy (HR 2.29, 95% CI 1.80–2.70). Hospitalization risk was also elevated (HR 1.22, 95% CI 1.05–1.41; P=0.009), particularly when non-cardiovascular medications predominated. In contrast, studies examining guideline-directed medical therapy (GDMT) showed that appropriate polypharmacy could mitigate risk and improve survival, especially in HFpEF and HFmrEF populations. Quality of life outcomes were inconsistent, with most studies reporting no significant association; modest improvements were observed when inappropriate medications were discontinued. Frailty amplified risks of mortality and functional decline. Conclusion: Polypharmacy in elderly heart failure patients is associated with higher mortality and hospitalization, particularly in the presence of frailty or inappropriate prescribing. However, polypharmacy driven by GDMT may confer survival benefits, underscoring the importance of medication appropriateness. Targeted deprescribing interventions and phenotype-specific management may reduce harm and improve outcomes in this vulnerable population.

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