The Effect of Crackers Enriched with Camelina Sativa Oil on Omega-3 Serum Fatty Acid Composition in Older Adults: A Randomized Placebo-Controlled Pilot Trial

{"Background": "Aging is associated with a chronic low-grade inflammatory state known as 'inflamm-ageing,' which contributes to metabolic dysfunction, frailty, and age-related diseases including cardiovascular disease, neurodegeneration, and type 2 diabetes. Omega-3 polyunsaturated fatty acids (\u03c9-3 PUFA), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have recognized anti-inflammatory properties, but dietary intake recommendations are often unmet due to poor dietary choices, cost, or concerns about fish contaminants. Camelina sativa oil is one of the richest plant-based sources of omega-3, with polyunsaturated fatty acid content exceeding 50%, alpha-linolenic acid (ALA) around 40\u201345%, and linoleic acid (LA) about 15%, along with antioxidant tocopherols. This study aimed to evaluate whether crackers enriched with Camelina sativa oil could increase serum omega-3 concentrations, improve inflammatory markers, and favorably alter the lipid profile in free-living older adults.", "Methods": "This double-blind, randomized, placebo-controlled pilot trial was conducted at Complife Italia s.r.l. (Milan, Italy) from June 2019 to March 2021, as part of the larger FoodNET project. Of 135 eligible Caucasian subjects aged \u226565 years, 66 volunteers (21 male, 45 female; mean age 70.6\u00b14.5 years) provided consent and were randomized 1:1 to the Camelina group (n=34) or placebo group (n=32). Exclusion criteria included hepatic/renal disease, bleeding disorders, mental/neurological disorders, severe eating disorders, and long-term vitamin/EPA/DHA supplementation. The Camelina group consumed 35 g of Camelina sativa oil-enriched crackers twice daily for 12 weeks (providing approximately 2.6 g ALA daily), while the placebo group consumed identical crackers without Camelina oil. Blood samples were collected at baseline (T0) and after 12 weeks (T1). Primary outcomes were serum polyunsaturated fatty acid profile (ALA, EPA, DHA, LA, ARA) measured by UHPLC-MS/MS. Secondary outcomes included inflammatory markers (IL-18, TNF-alpha, TGF-beta 1, TGF-beta 2, CRP) measured by bead-based multiplex assay, and serum lipid panel (total cholesterol, HDL, LDL, triglycerides) measured by routine methods. Anthropometric data, body composition (bioelectrical impedance analysis), epicardial fat thickness (echocardiography), dietary habits (validated questionnaire), and physical activity (IPAQ short form) were assessed at baseline. Statistical analysis used t-tests for between-group comparisons of T1-T0 differences, with regression analyses adjusting for smoking, eating habits, and statin use. Sample size calculation (26 per group) was based on detecting a 0.8 \u00b5g/mL difference in ALA with \u03b1<0.05 and \u03b2>0.80. Due to COVID-19 restrictions, 14 participants dropped out, leaving 50 completers; per-protocol analysis was used as dropouts did not differ from completers.", "Key Results": "The Camelina and placebo groups were well-matched at baseline for age, BMI (26.6\u00b14.04 kg/m\u00b2 overall), waist circumference, epicardial fat, phase angle, physical activity, and smoking habits. The placebo group had significantly healthier eating habits at baseline (59.5\u00b16.77 vs. 55.6\u00b16.51; p=0.032). After 12 weeks, the Camelina group showed a significantly greater increase in mean serum ALA concentration compared to placebo (mean difference T1-T0: 12.6\u00b19.32 vs. 5.9\u00b14.75; p=0.0046). No significant between-group differences were observed for EPA (2.5\u00b14.17 vs. 0.9\u00b11.47; p=0.0834), DHA (\u22120.5\u00b11.66 vs. \u22121.1\u00b11.74; p=0.2307), LA (37.2\u00b142.86 vs. 29.7\u00b135.83; p=0.5189), or ARA (4.7\u00b14.46 vs. 5.4\u00b13.97; p=0.5596). For inflammatory markers, a significant decrease in mean IL-18 concentration was observed in the placebo group compared to the Camelina group (\u221235.4\u00b151.6 vs. \u22125.4\u00b135.46; p=0.0198). No significant differences were found for TNF-alpha (13.3\u00b115.16 vs. 7.6\u00b122.47; p=0.3103), TGF-beta 1 (\u22125071\u00b110673.71 vs. \u22122497.1\u00b111474.48; p=0.4201), TGF-beta 2 (\u221269.4\u00b1130.22 vs. \u221283.4\u00b1174.22; p=0.7586), or CRP (\u2212188277.9\u00b12030081 vs. \u2212505799.2\u00b1735335.2; p=0.4749). Adjusted analyses for smoking and eating habits did not change these results. For lipid profile, no significant between-group differences were found for total cholesterol (\u22123.9\u00b127.22 vs. \u22120.5\u00b118.5; p=0.6085), HDL (0\u00b14.75 vs. \u22120.7\u00b15.22; p=0.6578), LDL (\u22125.8\u00b126.08 vs. 0.7\u00b120.97; p=0.3436), or triglycerides (\u22126.8\u00b123.77 vs. \u22124.9\u00b122.06; p=0.7724), though the Camelina group showed numerically greater reductions in TC, LDL, and TG. Adjustment for statin use (4 subjects) did not alter results.", "Clinical Implications": "This study demonstrates that Camelina sativa oil-enriched crackers can effectively increase serum ALA concentrations in older adults, offering a plant-based, sustainable alternative to fish-derived omega-3 sources. The lack of significant changes in downstream EPA and DHA levels suggests inefficient bioconversion of ALA, potentially due to competition with dietary LA for desaturase and elongase enzymes. The absence of significant anti-inflammatory effects (and the unexpected IL-18 decrease in the placebo group) may reflect this limited conversion, as well as the relatively low ALA dose (~2.6 g/day) compared to prior studies using pure camelina oil (10\u201311.4 g ALA/day). The non-significant trends toward greater reductions in total cholesterol, LDL, and triglycerides in the Camelina group are consistent with previous camelina oil studies that achieved statistical significance with larger sample sizes or higher doses. Given that over 50% of older adults have one or more non-communicable diseases, and that inflamm-ageing underlies many age-related conditions, Camelina oil-enriched functional foods represent a promising, accessible strategy for improving omega-3 status in older populations. However, the small sample size, high dropout rate due to COVID-19, and per-protocol analysis limit the strength of conclusions. Larger, adequately powered trials are needed to confirm effects on inflammatory markers and lipid profiles, and to determine optimal dosing for clinical benefit."}