Effect of Micronutrient Supplementation on the Intestinal Microbiota in Patients With Age-related Macular Degeneration - The Gut-Retina-axis Study
- Conditions
- Age-Related Macular Degeneration
- Interventions
- Dietary Supplement: a micronutrient mix containing lutein (10 mg), zeaxanthin (2 mg), saffron (20 mg), vitamin C (80 mg), vitamin E (12 mg) and zinc (10mg)Drug: anti-VEGF treatment
- Registration Number
- NCT06391411
- Lead Sponsor
- Azienda Ospedaliero-Universitaria Careggi
- Brief Summary
Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly, characterized by multifactorial etiology. Recent evidence suggests a potential involvement of the gut-retina axis in AMD pathogenesis, prompting exploration into novel therapeutic strategies. The investigators assessed the effects of a micronutrient mix containing lutein, zeaxanthin, and saffron, recognized for their anti-inflammatory properties, on ophthalmological and microbial parameters in neovascular AMD (nAMD) patients. Thirty nAMD subjects were randomized to receive daily micronutrient supplementation along with anti-VEGF therapy or anti-VEGF treatment alone for 6 months. Ophthalmological assessments, anthropometric and biochemical measurements and stool samples were obtained pre- and post-treatment. Gut microbiota (GM) characterization was performed through 16S rRNA sequencing while short (SCFAs), medium (MCFAs) and long (LCFAs) chain fatty acids were analyzed with a gas chromatography-mass spectrometry protocol. nAMD patients exhibited reduced GM alpha diversity, altered taxonomic abundances and decreased total SCFA amount, coupled with elevated proinflammatory octanoic and nonanoic acids. Micronutrient supplementation led to improved visual acuity in comparison to the control group, along with the reduction in the total amount of MCFAs, metabolites exerting detrimental ocular effects. This study reveals compositional and functional imbalances in the GM of nAMD patients compared to healthy controls. Furthermore micronutrient supplementation demonstrated a potential to restore the gut-retina axis, suggesting its therapeutic efficacy in improving ocular outcomes in nAMD patients. These findings underscore the intricate interplay between the GM and ocular health, offering insights into innovative interventions for AMD management
- Detailed Description
Age-related macular degeneration (AMD) stands as the primary cause of visual impairment in the over-65-year-old population of industrialized countries, affecting approximately 170 million people worldwide . AMD is a multifactorial disease in the pathogenesis of which, that it's not yet fully understood, genetic and environmental factors are involved. Specifically, there are two main types of AMD, both culminating in central vision deficiency and potential blindness due to the death of photoreceptors. The first type of AMD type, known as dry AMD, is characterized by the accumulation of extracellular material (i.e. lipids, vitronectin, inflammatory or amyloid proteins) between the Bruch's membrane and the retinal pigment epithelium, leading to the formation of drusen. Drusen are small yellow or white spots on the retina that can gradually evolve either into retinal and pigment epithelium atrophy or, for approximately 20% of patients, progress into the second AMD type that is called wet AMD or neovascular AMD (nAMD). nAMD is distinguished by the development of new choroidal vessels, a condition that can result in permanent visual impairment. Presently, although therapeutic options for dry AMD are limited, nAMD is treated with intravitreal injections of anti-VEGF (vascular endothelial growth factor) drugs, which have proven effective in slowing angiogenic development and limiting the progression of nAMD. Moreover, recent investigations have implicated immune system alterations, oxidative stress, and overweight as critical factors in AMD pathogenesis. Particularly, many studies have recently highlighted the potential benefits of dietary supplementation with micronutrients having antioxidant and antiinflammatory effects in reducing the risk of AMD development. Notably, the AREDS2 study definitively demonstrated the efficacy of dietary supplementation with lutein and zeaxanthin in reducing the risk of progression of early-stage AMD. In detail, the administration of lutein and zeaxanthin, which can absorb blue light and neutralize free radicals and reactive oxygen species in the macula, has been associated with increased macular pigment optical density (MPOD), improved visual acuity and a reduced risk of retinal aging. Moreover, other micronutrients such as vitamins E and C can prevent the progression of maculopathy by providing protection against oxidative stress and maintaining GM homeostasis while oral zinc supplementation can reduce the complement-mediated inflammation in the retinal pigment epithelium, which plays a fundamental role in the etiology of AMD. Additionally, saffron (Crocus sativus), which contains active components such as crocin, safranal, crocetin, and picrocrocin, has demonstrated antioxidant and anti-inflammatory effects, leading to significant improvements in the retinal function of AMD patients. Furthermore, considering that the retina is an extension of the brain both anatomically and developmentally, the hypothesis of a gut-retina interplay has been recently proposed, paralleling the widely explored bidirectional communication between the gut and the brain. Objectives of the study To evaluate the GM composition and function of nAMD patients in comparison to healthy subjects and considering the dual potential of micronutrients to act through direct antioxidant mechanisms and modulation of the GM, the investigators assessed the impact of a novel micronutrient supplementation based on lutein, zeaxanthin and saffron on ophthalmological parameters and microbial features of nAMD patients.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 45
- Men and women >50 years of age.
- Willingness to cooperate during the study and ability to follow guidelines and to complete all clinical visits
- Ability to provide informed consent
- Use of antibiotics or continued use of pre- or probiotics in the 2 months before enrolment
- Use of other treatments (medications or nutritional programs) that affect body weight, food intake, and/or energy expenditure
- Diagnosis of any ocular disease.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Micronutrient supplementation+ Aflibercept 2 mg, 0.05 ml a micronutrient mix containing lutein (10 mg), zeaxanthin (2 mg), saffron (20 mg), vitamin C (80 mg), vitamin E (12 mg) and zinc (10mg) Patients received intravitreal injections of anti-VEGF (Aflibercept 2 mg, 0.05 ml) at a fixed regimen and daily supplementation with a micronutrient mix containing lutein (10 mg), zeaxanthin (2 mg), saffron (20 mg), vitamin C (80 mg), vitamin E (12 mg) and zinc (10mg) for 6 months Aflibercept 2 mg, 0.05 ml anti-VEGF treatment Patients received only intravitreal injections of anti-VEGF (Aflibercept 2 mg, 0.05 ml) for 6 months Micronutrient supplementation+ Aflibercept 2 mg, 0.05 ml anti-VEGF treatment Patients received intravitreal injections of anti-VEGF (Aflibercept 2 mg, 0.05 ml) at a fixed regimen and daily supplementation with a micronutrient mix containing lutein (10 mg), zeaxanthin (2 mg), saffron (20 mg), vitamin C (80 mg), vitamin E (12 mg) and zinc (10mg) for 6 months
- Primary Outcome Measures
Name Time Method Changes in gut microbiota composition At baseline and at month 6 Changes in gut microbiota composition assessed by 16S sequencing
Changes in gut microbiota function At baseline and at month 6 Changes in gut microbiota function (quantification of short-, medium- and long-chain fatty acids)assessed with gas chromatography-mass spectrometry
Ophthalmological examination At baseline and at month 6 Ophthalmological examination with best correct visual acuity (BCVA), biomicroscopy and swept optical coherence tomography (OCT)
- Secondary Outcome Measures
Name Time Method Evaluation of Interleukin-6 At baseline and at month 6 Triglycerides At baseline and at month 6 Quantification with standard laboratory procedures
White blood cells At baseline and at month 6 Quantification with standard laboratory procedures
Platelets At baseline and at month 6 Quantification with standard laboratory procedures
Glucose At baseline and at month 6 Quantification with standard laboratory procedures
HDL-cholesterol At baseline and at month 6 Quantification with standard laboratory procedures
LDL-cholesterol At baseline and at month 6 Quantification with standard laboratory procedures
Red blood cells At baseline and at month 6 Quantification with standard laboratory procedures
Hemoglobin At baseline and at month 6 Quantification with standard laboratory procedures
Evaluation of tumor necrosis factor-α (TNF-α) At baseline and at month 6 Evaluation of Interleukin-10 At baseline and at month 6
Trial Locations
- Locations (1)
Unit of Clinical Nutrition, University Hospital of Careggi
🇮🇹Florence, Italy