Safety and Preliminary Effectiveness of a Natural, Multi-modal Therapeutic in Postmenopausal Women with Obesity

IntroductionPostmenopausal women exhibit increased central obesity due to aging-related alterations in hormones leading to adverse metabolic and biological consequences. The present study aimed to evaluate the safety of a natural, multi-modal therapeutic and observe alterations in metabolic and aging-related outcomes in humans for the first time. MethodsA non-comparer pilot study was conducted to translate preclinical findings of a glycation-lowering supplement (Alpha-lipoic acid, nicotinamide, thiamine, piperine, pyridoxamine) to postmenopausal women with obesity [n=85; >55 years; BMI=35.0{+/-}4.35/30.3-42.8 (Figure 1)]. Qualified participants (n=13) consumed two capsules daily for 6 months. Complete Blood Count [e.g. (Red Cell Distribution Width (RDW%)], Mean Corpuscular Volume (MCH), etc.], depression (Center for Epidemiologic Studies Depression Scale), insulin resistance [Homeostatic Model (HOMA-IR)], fat oxidation [respiratory quotient (RQ)], weight/height, waist circumference (WC), bone mineral density (BMD) by Dual-Energy X-ray Absorptiometry, low (LDL) and high density (HDL) lipoproteins, phenotypic age (PA), follicle stimulating hormone (FSH) caloric intake [(CI)-NIH/NIS/ASA 24-2020 Dietary Assessment], and immediate recall [(IM) BrainCheck] were assessed at baseline and 6-month-follow-up. O_FIG O_LINKSMALLFIG WIDTH=158 HEIGHT=200 SRC="FIGDIR/small/25335119v1_fig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@59448borg.highwire.dtl.DTLVardef@a329dcorg.highwire.dtl.DTLVardef@114ebforg.highwire.dtl.DTLVardef@48dea8_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1C_FLOATNO Flow of Participants through Each Stage of the Pilot Clinical Trial (CONSORT Flowchart) C_FIG ResultsNo serious adverse events were reported. Six participants reporting mild/moderate adverse events were lost to follow-up. Mixed-effect models (intent-to-treat analysis) compared outcomes prior to (n=13) and following (n=7) the 6-month intervention. RDW% (p=0.009), MCV (p=0004), RQ (p=0.02), WC (p=0.02), HDL (p=0.044), phenotypic age (p=0.037), FSH (0.002), and CI (p=0.01) significantly decreased. Depression (p=0.002), height (p=0.003), BMD (p=0.02) and IM (p=0.04) significantly increased; HOMA-IR and LDL were unchanged. ConclusionsPreliminary results indicate that a natural, multi-modal therapeutic is safe in postmenopausal women with obesity. Several metabolic and aging-related outcomes improved following the intervention. However, decreased HDL, RDW%, MCV and increased depression warrant further investigation in future randomized-controlled trials. Clinicaltrials.gov #NCT06242535