Manuka honey's anti-metastatic impact on colon cancer stem-like cells: unveiling its effects on epithelial-mesenchymal transition, angiogenesis and telomere length.

Colorectal cancer often leads to metastasis, with cancer stem cells (CSCs) playing a pivotal role in this process. Two closely linked mechanisms, epithelial-mesenchymal transition and angiogenesis, contribute to metastasis and recent research has also highlighted the impact of telomere replication on this harmful tumor progression. Standard chemotherapy alone can inadvertently promote drug-resistant CSCs, posing a challenge. Combining chemotherapy with other compounds, including natural ones, shows promise in enhancing effectiveness while minimizing side effects. This study investigated the anti-metastatic potential of Manuka honey, both alone and in combination with 5-fluorouracil, using a 3D model of colonospheres enriched with CSC-like cells. In summary, it was observed that the treatment reduced migration ability by downregulating the transcription factors Slug, Snail, and Twist, which are key players in epithelial-mesenchymal transition. Additionally, Manuka honey downregulated pro-angiogenic factors and shortened CSC telomeres by downregulating c-Myc - demonstrating an effective anti-metastatic potential. This study suggests new research opportunities for studying the impact of natural compounds when combined with pharmaceuticals, with the potential to enhance effectiveness and reduce side effects.

In Vitro and In Vivo Insights into a Broccoli Byproduct as a Healthy Ingredient for the Management of Alzheimer's Disease and Aging through Redox Biology.

Broccoli has gained popularity as a highly consumed vegetable due to its nutritional and health properties. This study aimed to evaluate the composition profile and the antioxidant capacity of a hydrophilic extract derived from broccoli byproducts, as well as its influence on redox biology, Alzheimer's disease markers, and aging in the Caenorhabditis elegans model. The presence of glucosinolate was observed and antioxidant capacity was demonstrated both in vitro and in vivo. The in vitro acetylcholinesterase inhibitory capacity was quantified, and the treatment ameliorated the amyloid-ß- and tau-induced proteotoxicity in transgenic strains via SOD-3 and SKN-1, respectively, and HSP-16.2 for both parameters. Furthermore, a preliminary study on aging indicated that the extract effectively reduced reactive oxygen species levels in aged worms and extended their lifespan. Utilizing broccoli byproducts for nutraceutical or functional foods could manage vegetable processing waste, enhancing productivity and sustainability while providing significant health benefits.

Effect of olive leaf phytochemicals on the anti-acetylcholinesterase, anti-cyclooxygenase-2 and ferric reducing antioxidant capacity.

In this study, the phytochemical profile of fifty olive leaves (OL) extracts from Spain, Italy, Greece, Portugal, and Morocco was characterized and their anti-cholinergic, anti-inflammatory, and antioxidant activities were evaluated. Luteolin-7-O-glucoside, isoharmnentin, and apigenin were involved in the acetylcholinesterase (AChE) inhibitory activity, while oleuropein and hydroxytyrosol showed noteworthy potential. Secoiridoids contributed to the cyclooxygenase-2 inhibitory activity and antioxidant capacity. Compounds such as oleuropein, ligstroside and luteolin-7-O-glucoside, may exert an important role in the ferric reducing antioxidant capacity. It should be also highlighted the role of hydroxytyrosol, hydroxycoumarins, and verbascoside concerning the antioxidant activity. This research provides valuable insights and confirms that specific compounds within OL extracts contribute to distinct anti-cholinergic, anti-inflammatory, and anti-oxidative effects.

Valorization of Olea europaea and olive oil processing by-products/wastes.

Olive (Olea europaea) is a native species from the Mediterranean region and widely cultivated for its edible fruit, known as olives. Olives are a rich source of monounsaturated fatty acids, vitamin E, and polyphenols, and have been shown to have various health benefits. They are commonly used for cooking and are also employed in cosmetics and the pharmaceutical industry. The extract obtained from olive fruits and several subproducts of the olive industry has demonstrated several biological activities mainly associated with their antioxidant and inflammatory properties. Thus, olives, olive-derived products, and subproducts of the olive industry have gained popularity in recent years due to their potential health benefits and their use in traditional medicine. The present chapter summarizes the main applications of Olea europaea and olive oil processing by-products as therapeutic agents against cancer, cardiovascular diseases, and antimicrobial agents.

Exploring the Antioxidant, Neuroprotective, and Anti-Inflammatory Potential of Olive Leaf Extracts from Spain, Portugal, Greece, and Italy.

The leaves of the olive tree (Olea europaea L.) are one of the major solid wastes from the olive industry. Globally, the European Union is the largest producer of olive by-products, with Spain, Italy, Greece, and Portugal accounting for almost the entire production. Many questions remain to be solved concerning olive leaves (OL), including those related to possible differences in composition and/or biological activities depending on their geographical origin. In the present work, OL from Spain, Italy, Greece, and Portugal have been characterized according to their phytochemical profile, antioxidant capacity, neuroprotective activity, and anti-inflammatory effects. The Spanish and Italian OL samples presented the highest antioxidant and neuroprotective activities, while the Greek OL showed the lowest. These results were strongly associated with the content of oleoside methyl ester and p-hydroxybenzoic acid for the Spanish and Italian samples, respectively, whereas the content of decarboxymethyl elenolic acid dialdehyde form (hydrated) was negatively associated with the mentioned biological activities of the Greek samples. No country-related effect was observed in the anti-inflammatory activity of OL. Comprehensively, this work could provide a useful tool for manufacturers and R&D departments in making environmentally friendly decisions on how OL can be used to generate nutraceutical products based on the composition and origin of this by-product.

Dietary antioxidants and lifespan: Relevance of environmental conditions, diet, and genotype of experimental models.

The rise of life expectancy in current societies is not accompanied, to date, by a similar increase in healthspan, which represents a great socio-economic problem. It has been suggested that aging can be manipulated and then, the onset of all age-associated chronic disorders can be delayed because these pathologies share age as primary underlying risk factor. One of the most extended ideas is that aging is consequence of the accumulation of molecular damage. According to the oxidative damage theory, antioxidants should slow down aging, extending lifespan and healthspan. The present review analyzes studies evaluating the effect of dietary antioxidants on lifespan of different aging models and discusses the evidence on favor of their antioxidant activity as anti-aging mechanisms. Moreover, possible causes for differences between the reported results are evaluated.

Possible role of nutrition in the prevention of inflammatory bowel disease-related colorectal cancer: A focus on human studies.

Patients with inflammatory bowel disease (IBD) are at substantially high risk for colorectal cancer (CRC). IBD-associated CRC accounts for roughly 10% to 15% of the annual mortality in patients with IBD. IBD-related CRC also affects younger patients compared with sporadic CRC, with a 5-y survival rate of 50%. Regardless of medical therapies, the persistent inflammatory state characterizing IBD raises the risk for precancerous changes and CRC, with additional input from several elements, including genetic and environmental risk factors, IBD-associated comorbidities, intestinal barrier dysfunction, and gut microbiota modifications. It is well known that nutritional habits and dietary bioactive compounds can influence IBD-associated inflammation, microbiome abundance and composition, oxidative stress balance, and gut permeability. Additionally, in recent years, results from broad epidemiologic and experimental studies have associated certain foods or nutritional patterns with the risk for colorectal neoplasia. The present study aimed to review the possible role of nutrition in preventing IBD-related CRC, focusing specifically on human studies. It emerges that nutritional interventions based on healthy, nutrient-dense dietary patterns characterized by a high intake of fiber, vegetables, fruit, ω-3 polyunsaturated fatty acids, and a low amount of animal proteins, processed foods, and alcohol, combined with probiotic supplementation have the potential of reducing IBD-activity and preventing the risk of IBD-related CRC through different mechanisms, suggesting that targeted nutritional interventions may represent a novel promising approach for the prevention and management of IBD-associated CRC.

Molecular Mechanisms of the Protective Effects of Olive Leaf Polyphenols against Alzheimer's Disease.

Alzheimer's Disease (AD) is the cause of around 60-70% of global cases of dementia and approximately 50 million people have been reported to suffer this disease worldwide. The leaves of olive trees (Olea europaea) are the most abundant by-products of the olive grove industry. These by-products have been highlighted due to the wide variety of bioactive compounds such as oleuropein (OLE) and hydroxytyrosol (HT) with demonstrated medicinal properties to fight AD. In particular, the olive leaf (OL), OLE, and HT reduced not only amyloid-ß formation but also neurofibrillary tangles formation through amyloid protein precursor processing modulation. Although the isolated olive phytochemicals exerted lower cholinesterase inhibitory activity, OL demonstrated high inhibitory activity in the cholinergic tests evaluated. The mechanisms underlying these protective effects may be associated with decreased neuroinflammation and oxidative stress via NF-κB and Nrf2 modulation, respectively. Despite the limited research, evidence indicates that OL consumption promotes autophagy and restores loss of proteostasis, which was reflected in lower toxic protein aggregation in AD models. Therefore, olive phytochemicals may be a promising tool as an adjuvant in the treatment of AD.

In Vivo Anti-Alzheimer and Antioxidant Properties of Avocado (Persea americana Mill.) Honey from Southern Spain.

There is growing evidence that Alzheimer's disease (AD) can be prevented by reducing risk factors involved in its pathophysiology. Food-derived bioactive molecules can help in the prevention and reduction of the progression of AD. Honey, a good source of antioxidants and bioactive molecules, has been tied to many health benefits, including those from neurological origin. Monofloral avocado honey (AH) has recently been characterized but its biomedical properties are still unknown. The aim of this study is to further its characterization, focusing on the phenolic profile. Moreover, its antioxidant capacity was assayed both in vitro and in vivo. Finally, a deep analysis on the pathophysiological features of AD such as oxidative stress, amyloid-ß aggregation, and protein-tau-induced neurotoxicity were evaluated by using the experimental model C. elegans. AH exerted a high antioxidant capacity in vitro and in vivo. No toxicity was found in C. elegans at the dosages used. AH prevented ROS accumulation under AAPH-induced oxidative stress. Additionally, AH exerted a great anti-amyloidogenic capacity, which is relevant from the point of view of AD prevention. AH exacerbated the locomotive impairment in a C. elegans model of tauopathy, although the real contribution of AH remains unclear. The mechanisms under the observed effects might be attributed to an upregulation of daf-16 as well as to a strong ROS scavenging activity. These results increase the interest to study the biomedical applications of AH; however, more research is needed to deepen the mechanisms under the observed effects.

Bioactive Properties of Tagetes erecta Edible Flowers: Polyphenol and Antioxidant Characterization and Therapeutic Activity against Ovarian Tumoral Cells and Caenorhabditis elegans Tauopathy.

Tagetes erecta is an edible flower deeply rooted in traditional Mexican culture. It holds a central role in the most popular and iconic Mexican celebration, "the Day of the Dead". Furthermore, it is currently receiving interest as a potential therapeutic agent, motivated mainly by its polyphenol content. The present study aims to evaluate the biological activity of an extract synthesized from the petals of the edible flower T. erecta. This extract showed significant antioxidant scores measured by the most common in vitro methodologies (FRAP, ABTS, and DPPH), with values of 1475.3 µM trolox/g extr, 1950.3 µM trolox/g extr, and 977.7 µM trolox/g extr, respectively. In addition, up to 36 individual polyphenols were identified by chromatography. Regarding the biomedical aspects of the petal extract, it exhibited antitumoral activity against ovarian carcinoma cells evaluated by the MTS assay, revealing a lower value of IC50 compared to other flower extracts. For example, the extract from T. erecta reported an IC50 value half as low as an extract from Rosa × hybrida and six times lower than another extract from Tulbaghia violacea. This antitumoral effect of T. erecta arises from the induction of the apoptotic process; thus, incubating ovarian carcinoma cells with the petal extract increased the rate of apoptotic cells measured by flow cytometry. Moreover, the extract also demonstrated efficacy as a therapeutic agent against tauopathy, a feature of Alzheimer's disease (AD) in the Caenorhabditis elegans experimental model. Treating worms with the experimental extract prevented disfunction in several motility parameters such as wavelength and swimming speed. Furthermore, the T. erecta petal extract prevented the release of Reactive Oxygen Species (ROS), which are associated with the progression of AD. Thus, treatment with the extract resulted in an approximate 20% reduction in ROS production. These findings suggest that these petals could serve as a suitable source of polyphenols for biomedical applications.

Relation between Strawberry Fruit Redness and Bioactivity: Deciphering the Role of Anthocyanins as Health Promoting Compounds.

The red colour of most berries is often associated to fruit healthiness, since it has been linked to enrichment in anthocyanins (polyphenol with antioxidative properties). However, recent studies suggest that anthocyanins could not be the major contributors to bioactivity leading to uncertainty about their role as important molecules in the generation of health-promoting properties. To shed light on this issue, spectrophotometric and HPLC techniques were used for characterizing the content of phenolic compounds, including anthocyanins, in fruits of red (Fragaria x ananassa, cv. Fortuna) and white strawberry (Fragaria vesca spp. XXVIII) species (distinguishing receptacle from achene). In addition, the effect of these extracts on the reduction of intracellular ROS was tested, as well as on the activity of antioxidant enzymes and the quantification of cell oxidation markers. The results showed that white receptacle extracts (deprived of anthocyanins) were able to protect cells from oxidative damage to a greater extent than red fruits. This could be due per se to their high antioxidant capacity, greater than that shown in red fruits, or to the ability of antioxidants to modulate the activity of antioxidant enzymes, thus questioning the positive effect of anthocyanins on the wholesomeness of strawberry fruits. The results shed light on the relevance of anthocyanins in the prevention of health-associated oxidative damage.

Amyloid ß-but not Tau-induced neurotoxicity is suppressed by Manuka honey via HSP-16.2 and SKN-1/Nrf2 pathways in an in vivo model of Alzheimer's disease.

Alzheimer's is a chronic degenerative disease of the central nervous system considered the leading cause of dementia in the world. It is characterized by two etiopathological events related to oxidative stress: the aggregation of ß-amyloid peptide and the formation of neurofibrillary tangles of hyperphosphorylated Tau protein in the brain. The incidence of this disease increases with age and has been associated with inadequate lifestyles. Some natural compounds have been shown to improve the hallmarks of the disease. However, despite its potential, there is no scientific evidence about Manuka honey (MH) in this regard. In the present work we evaluated the effect of MH on the toxicity induced by Aß aggregation and Tau in a Caenorhabditis elegans model. Our results demonstrated that MH was able to improve indicators of oxidative stress and delayed Aß-induced paralysis in the AD model CL4176 through HSP-16.2 and SKN-1/NRF2 pathways. Nevertheless, its sugar content impaired the indicators of locomotion (an indicator of tau neurotoxicity) in both the transgenic strain BR5706 and in the wild-type N2 worms.

Molecular bases for the use of functional foods in the management of healthy aging: Berries, curcumin, virgin olive oil and honey; three realities and a promise.

As the number of older people has grown in recent decades, the search for new approaches to manage or delay aging is also growing. Among the modifiable factors, diet plays a crucial role in healthy aging and in the prevention of age-related diseases. Thus, the interest in the use of foods, which are rich in bioactive compounds such as functional foods with anti-aging effects is a growing market. This review summarizes the current knowledge about the molecular mechanisms of action of foods considered as functional foods in aging, namely berries, curcumin, and virgin olive oil. Moreover, honey is also analyzed as a food with well-known healthy benefits, but which has not been deeply evaluated from the point of view of aging. The effects of these foods on aging are analyzed from the point of view of molecular mechanisms including oxidative stress, mitochondrial dysfunction, inflammation, genomic stability, telomere attrition, cellular senescence, and deregulated nutrient-sensing. A comprehensive study of the scientific literature shows that the aforementioned foods have demonstrated positive effects on certain aspects of aging, which might justify their use as functional foods in elderly. However, more research is needed, especially in humans, designed to understand in depth the mechanisms of action through which they act.

Adherence to the Mediterranean-Style Eating Pattern and Macular Degeneration: A Systematic Review of Observational Studies.

Age-related macular degeneration (AMD) is a serious degenerative disease affecting the eyes, and is the main cause of severe vision loss among people >55 years of age in developed countries. Its onset and progression have been associated with several genetic and lifestyle factors, with diet appearing to play a pivotal role in the latter. In particular, dietary eating patterns rich in plant foods have been shown to lower the risk of developing the disease, and to decrease the odds of progressing to more advanced stages in individuals already burdened with early AMD. We systematically reviewed the literature to analyse the relationship between the adherence to a Mediterranean diet, a mainly plant-based dietary pattern, and the onset/progression of AMD. Eight human observational studies were analysed. Despite some differences, they consistently indicate that higher adherence to a Mediterranean eating pattern lowers the odds of developing AMD and decreases the risk of progression to more advanced stages of the disease, establishing the way for preventative measures emphasizing dietary patterns rich in plant-foods.

An Olive-Derived Extract 20% Rich in Hydroxytyrosol Prevents ß-Amyloid Aggregation and Oxidative Stress, Two Features of Alzheimer Disease, via SKN-1/NRF2 and HSP-16.2 in Caenorhabditis elegans.

Olive milling produces olive oil and different by-products, all of them very rich in different bioactive compounds like the phenolic alcohol hydroxytyrosol. The aim of the present study was to investigate the effects of an olive fruit extract 20% rich in hydroxytyrosol on the molecular mechanisms associated with Alzheimer disease features like Aß- and tau- induced toxicity, as well as on oxidative stress in Caenorhabditis elegans. Moreover, characterization of the extracts, regarding the profile and content of phenolics, as well as total antioxidant ability, was investigated. The study of lethality, growth, pharyngeal pumping, and longevity in vivo demonstrated the lack of toxicity of the extract. One hundred µg/mL of extract treatment revealed prevention of oxidative stress and a delay in Aß-induced paralysis related with a lower presence of Aß aggregates. Indeed, the extract showed the ability to avoid a certain degree of proteotoxicity associated with aggregation of the tau protein. According to RNAi tests, SKN-1/NRF2 transcription factor and the overexpression of HSP-16.2 were mechanistically associated in the observed effects.

An oleuropein rich-olive (Olea europaea L.) leaf extract reduces ß-amyloid and tau proteotoxicity through regulation of oxidative- and heat shock-stress responses in Caenorhabditis elegans.

Olive tree-derived products have been associated with numerous benefits for health. The aim of the present study was to characterize an olive leaf extract enriched in oleuropein (OLE) concerning phenolic content and profile as well as antioxidant capacity. Short-term and long-term toxicity, including oxidative stress, was in vivo evaluated in the experimental model Caenorhabditis elegans. Moreover, the potential therapeutic effect of the extract against Aß induced- and tau protein induced-toxicity was also evaluated in C. elegans. OLE treatment did not exert toxicity. On the contrary, the extract was able to ameliorate oxidative stress and proteotoxicity related to Aß and tau aggregation. The potential molecular mechanisms present behind the observed results explored by RNAi technology revealed that DAF-16/FOXO and SKN-1/NRF2, elements of the insulin insulin-like signalling pathway, as well as HSP-16.2 overexpression were involved.

The Effect of Dietary Polyphenols on Vascular Health and Hypertension: Current Evidence and Mechanisms of Action.

The aim of this review was to explore existing evidence from studies conducted on humans and summarize the mechanisms of action of dietary polyphenols on vascular health, blood pressure and hypertension. There is evidence that some polyphenol-rich foods, including berry fruits rich in anthocyanins, cocoa and green tea rich in flavan-3-ols, almonds and pistachios rich in hydroxycinnamic acids, and soy products rich in isoflavones, are able to improve blood pressure levels. A variety of mechanisms can elucidate the observed effects. Some limitations of the evidence, including variability of polyphenol content in plant-derived foods and human absorption, difficulty disentangling the effects of polyphenols from other dietary compounds, and discrepancy of doses between animal and human studies should be taken into account. While no single food counteracts hypertension, adopting a plant-based dietary pattern including a variety of polyphenol-rich foods is an advisable practice to improve blood pressure.

Effect of Brazil Nuts on Selenium Status, Blood Lipids, and Biomarkers of Oxidative Stress and Inflammation: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Tree nuts, including Brazil nuts, have been hypothesized to impact cardiovascular health through the modulation of oxidative stress and inflammation. Nonetheless, a quantitative analysis of these effects has not been performed. Therefore, the aim of this study was to systematically revise and quantify the effect of Brazil nut intervention on selenium status, blood lipids, and biomarkers of oxidative stress and inflammation using a meta-analytical approach. To meet the goals of this study, a systematic search of PubMed, EMBASE, and Web of Science databases of published randomised clinical trials reporting on dietary interventions with Brazil nuts and their effects on selenium status, blood lipids, and markers of oxidative stress and inflammation was performed. Eight articles were included for systematic review and meta-analysis. Based on the conducted analysis, a significant positive effect of Brazil nuts on selenium blood concentration (SMD = 6.93, 95% CI: 3.99; 9.87) was found. Additionally, a positive effect of Brazil nut intervention on glutathione peroxidase activity (SMD = 0.53, 95% CI: 0.07; 0.99) was observed. However, no significant results were found when considering blood lipid levels, including results for total cholesterol (SMD = -0.22, 95% CI: -0.57; 0.14), HDL cholesterol (SMD = -0.04, 95% CI: -0.28; 0.19) and LDL cholesterol (SMD = -0.15; 95% CI: -0.43; 0.13). In conclusion, the findings from this study suggest that Brazil nut consumption improves selenium status and exerts antioxidant effects, which could be considered a potential pathway for the prevention of metabolic disorders related to altered blood lipid profiles. However, further studies are needed to elucidate the effect of Brazil nuts toward blood lipid profile, also preferably controlling for other biomarkers.

Changes in the Lifestyle of the Spanish University Population during Confinement for COVID-19.

The aim of this study was to evaluate the influence of the lockdown due to the COVID-19 pandemic, on eating and physical activity behavior, in a university population. A healthy diet such as the Mediterranean Diet (MD) pattern, rich in fruit and vegetables, can prevent degenerative diseases such as obesity, diabetes, cardiovascular diseases, etc. We conducted a cross-sectional study and data were collected by an anonymous online questionnaire. Participants completed a survey consisting of 3 sections: sociodemographic data; dietary behavior and physical activity; the Mediterranean Diet questionnaire (MEDAS-14) and the Emotional Eater Questionnaire (EEQ). A total of 168 participants completed the questionnaire: 66.7% were women, 79.2% were from Spain, 76.8% were students, 76.2% lived in their family home and 66.1% were of normal weight. During lockdown our population shopped for groceries 1 time or less per week (76.8%); maintained the same consumption of fruits (45.2%), vegetables (50.6%), dairy products (61.9%), pulses (64.9%), fish/seafood (57.7%), white meat (77.4%), red and processed meat (71.4%), pastries and snacks (48.2%), rice/pasta/potatoes (70.2%) and nuts (62.5%), spirits (98.8%) and sugary drinks (91.7%). Cooking time increased (73.2%) and the consumption decreased of low alcohol drinks (60.1%), spirits (75%) and sugary drinks (57.1%), and physical activity also diminished (49.4%). University Employees (UE) gained more weight (1.01 ± 0.02) than students (0.99 ± 0.03) (p < 0.05) during the confinement period. A total of 79.8% of the participants obtained a Medium/High Adherence to the MD during lockdown. Emotional and very emotional eaters were higher in the female group (p < 0.01). In the event of further confinement, strategies should be implemented to promote a balanced and healthy diet together with the practice of physical activity, taking special care of the female and UE groups.

Alcohol Consumption, Bone Mineral Density, and Risk of Osteoporotic Fractures: A Dose-Response Meta-Analysis.

Excess alcohol consumption is known to be detrimental to human health. However, the role of light-to-moderate alcohol intake is under investigation for potential certain health benefits-mostly related to the cardiovascular system. Nevertheless, there is no univocal agreement on this matter, and research is still ongoing to clarify whether there might be other potential outcomes affected by alcohol intake. In this regard, there is evidence that excess alcohol intake may negatively influence the risk of osteoporotic fractures. However, there is no comprehensive evidence of literature assessing the role of alcohol consumption in bone mineral density (BMD) and the risk of osteoporotic fractures. Thus, the aim of this study was to quantitatively assess the dose-response relationship between alcohol intake and BMD and risk of osteoporotic fractures. The Embase and MEDLINE electronic databases were searched from their inception to December 2021 for articles providing a quantifiable measurement of alcohol consumption for at least three categories and (1) a measurement of BMD (and dispersion as continuous variables) in some area of the body or (2) risk of osteoporotic fracture provided as relative risk (RR) or hazard ratio (HR), with a 95% confidence interval (CI) as the measure of the association of each category with alcohol intake. A total of 11 studies including 46,916 individuals with BMD assessment and 8 studies including 240,871 individuals with risk of fracture analysis were included. Compared to non-drinkers, consumption of up to two standard drinks of alcohol per day was correlated with higher lumbar and femur neck BMD values, while up to one standard drink of alcohol was correlated with higher hip BMD compared to no alcohol consumption. Higher risk of hip fractures was found starting from three standard drinks of alcohol per day (RR = 1.33, 95% CI: 1.04; 1.69 for three alcoholic drinks/d, and RR = 1.59, 95% CI: 1.23; 2.05 for four alcoholic drinks/d) compared to no alcohol consumption, with no evidence of heterogeneity. Concerning the risk of any osteoporotic fractures, the risk steadily increased with higher intake of alcohol, although never reaching statistical significance. In conclusion, there is consistent evidence that increased alcohol consumption is associated with higher risk of osteoporotic hip fracture; however, the role of alcohol at lower doses is uncertain, as BMD was even higher in light drinkers compared to abstainers.