The association of sodium bicarbonate (NaHCO3) or NaHCO3-containing nanomaterials with tumor pH and immune response in cancer therapeutics

Advances in Cancer Biology - Metastasis · 2026-05-14

Tumor acidosis is a defining feature of solid tumors and contributes to invasion, metastasis, immune dysfunction, and resistance to chemotherapy and immunotherapy. This review examined whether sodium bicarbonate (NaHCO 3 ), a chemical compound that modifies extracellular pH is associated with tumor behavior and treatment outcomes. We reviewed preclinical and early clinical studies evaluating NaHCO 3 - and NaHCO 3 -containing nanomaterial-based approaches to tumor pH modulation. Studies were included if they reported primary experimental data assessing the effects of NaHCO 3 on tumor pH, tumor behavior, immune function, or therapeutic response. Studies were categorized based on mode of NaHCO 3 delivery. Fourteen studies met inclusion criteria. In eight studies using tumor-bearing mouse models, NaHCO 3 delivered through drinking water consistently elevated extracellular tumor pH without inducing systemic alkalosis. Furthermore, it reduced spontaneous metastases, improved survival, suppression of acid-activated enzymes involved in tissue breakdown, and enhanced anti-tumor immune activity, including improved T-cell function and cytokine production. Four studies using vitro systems or metastatic mouse models with selective localized delivery of NaHCO 3 -incorporating nanoparticles also achieved improved therapeutic outcomes compared with systemic delivery alone. Early clinical data and phase 0 studies of oral NaHCO 3 among humans indicate that long-term administration is feasible but limited by gastrointestinal tolerability. Tumor alkalinization may be a potential add-on to chemotherapy, targeted therapy, and immunotherapy. Localized approaches appear to offer potential advantages in efficiency and tolerability. However, further studies are needed to define optimal dosing strategies, delivery platforms, potential risks, and patient populations most likely to benefit from tumor pH-modulating therapies.

Higher fat-soluble vitamin and phosphorus intake are associated with less dental caries among children and adolescents in the United States, NHANES 2011–2018

Frontiers in Oral Health · 2025-07-09

Introduction Historic research shows that a diet rich in calcium, phosphorus, fat-soluble vitamins, and vitamin C, and low in phytates may help to prevent and arrest dental caries; however, current research on this topic is scarce. We examined associations of dietary intake of these nutrients with dental caries prevalence in the United States among youth 1–19 years old. Methods The study included 2,676 young children (1–5 years), 3,214 older children (6–11 years) and 3,701 adolescents (12–19 years) from the National Health and Nutrition Examination Survey (NHANES 2011–2018). Daily nutrient intake was ascertained via two 24 h recalls. We assessed the number and presence (yes/no) of decayed and/or filled teeth (DFT) among young children and decayed, missing and/or filled teeth (DMFT) among older children and adolescents. Covariate-adjusted survey-weighted negative binomial regression was used to examine associations of nutrient quartiles with DFT or DMFT scores. We examined joint associations of nutrients with the probability of caries using the probit extension of Bayesian Kernel Machine Regression. Results Mean (SD) DFT or DMFT scores were 0.82 (2.23) for young children, 2.08 (2.81) for older children and 2.51 (3.35) for adolescents. Higher phosphorus and vitamin A intake was associated with fewer DFT among young children [incident rate ratio (IRR) = 0.52, 95% CI: 0.29–0.94, p = 0.03, and IRR = 0.60, 95% CI: 0.37–0.95, p = 0.03, respectively]. Unexpectedly, higher intake of phytates was also associated with lower DFT scores among young children (IRR = 0.37, 95% CI: 0.21–0.65, p = 0.001). Higher phosphorus and vitamin E intake was associated with fewer DMFT among older children (IRR = 0.58, 95% CI: 0.40–0.84, p = 0.003 and IRR = 0.73, 95% CI: 0.54–0.97, p = 0.03, respectively). For adolescents, higher phosphorus and vitamin K intake was associated with fewer DMFT (IRR = 0.72, 95% CI: 0.53–0.99, p < 0.05; IRR = 0.82, 95% CI: 0.68–0.97, p = 0.02, respectively). The joint effect of nutrients was also associated with lower odds of DMFT. Setting all nutrients at their 75th relative to 50th percentiles was associated with 0.87 [95% credible interval (CrI): 0.81, 0.94] and 0.92 (95% CrI: 0.85, 0.99) lower odds of DMFT in older children and adolescents, respectively. Phosphorus and vitamin K contributed most to these associations. Conclusion Fat-soluble vitamins and phosphorus may have systemic dental benefits that warrant further investigation.

International fluoride symposium: effects of fluoride on human health and its mechanisms of action – a meeting report

BMC Proceedings · 2025-09-28 · 1 citations

Fluoride prevents dental caries in a dose-response manner, leading some countries to adjust fluoride levels in water or table salt, as well as to promote the widespread use of topical fluoride. Recent studies have found associations between prenatal fluoride exposure levels of < 1.5 mg/L in water and urine and adverse neurodevelopmental outcomes. Although high fluoride levels have been recognized as neurotoxic in the past, a large body of contemporary evidence derived from retrospective analyses of birth cohort studies suggests fluoride may be neurotoxic to children at lower levels, highlighting the need for further, prospective research and multidisciplinary collaborations. The International Fluoride Symposium, held from April 29 to 30, 2024, brought together 20 researchers from the United States, Canada, Mexico, and Spain to discuss the impacts of fluoride on human health and its mechanisms of action. The primary goals of the symposium were to address challenges related to assessing fluoride exposure, share findings from cohort studies, develop a comprehensive research agenda, and foster international research partnerships. Key discussions included the dental caries preventive and toxic effects of fluoride, sources of fluoride exposure, biomarkers, dietary intake assessment methods, and analytical challenges. Presentation of results from cohort studies highlighted research on prenatal fluoride exposure and its association with neurodevelopmental outcomes and presented perspectives for future analyses. The symposium emphasized the need for customized dietary fluoride intake assessment tools, the development of high-throughput analytical methods for fluoride analysis, and research on the combined effects of fluoride with other chemical elements commonly found in the environment and the human diet. Additionally, there was a call for the harmonization of cohort data from diverse populations to address urgent questions about the impact of fluoride on human neurodevelopment and other health outcomes beyond oral health. It was agreed that prospective longitudinal cohort studies intentionally designed to assess fluoride exposure and neurodevelopment are essential, as none of the existing birth cohorts were designed to specifically study fluoride exposure (e.g., selection of biomarkers, collection intervals, diet exposure assessment). Furthermore, broader environmental health cohort studies that incorporate high-quality biomonitoring of waterborne neurotoxicants (such as fluoride, arsenic, lead, mercury), repeated measures of exposure, and inclusion of key covariates (e.g., socio-economic status, diet, iodine) are encouraged. Finally, developing effective communication strategies among scientists and the public was considered crucial for advancing fluoride research and mitigating potential health risks.

Urinary fluoride and dental fluorosis in relation to kidney and liver function in adolescents and young adults in the United States

Environmental Health · 2025-10-31 · 1 citations

Higher fluoride in plasma has been associated with lower eGFR among adolescents in the National Health and Nutrition Examination Survey (NHANES); however, whether fluoride exposure may contribute to decreased kidney function or fluoride may accumulate in plasma from lower kidney filtration could not be parsed. We examined the presence of dental fluorosis (DF; reflecting chronic fluoride exposure during tooth development) among adolescents and young adults and urinary fluoride (UF) levels among adolescents in relation to kidney and liver parameters in the United States (US). Participants were 1,031 adolescents (aged 12–19 years) and 734 young adults (aged 20–29 years) from NHANES 2015–2016. DF was derived from Dean’s Fluorosis Index (DFI), and defined as any DFI score indicating very mild, mild, moderate, or severe fluorosis, while scores of normal and questionable were categorized as no fluorosis. Kidney or liver function parameters included estimated glomerular filtration rate (eGFR), serum uric acid, the urinary albumin to creatinine ratio, blood urea nitrogen (BUN), gamma glutamate transferase, aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase, and albumin. We conducted survey-weighted linear regression adjusted for covariates to examine associations between fluoride exposure and kidney or liver function. Adolescent participants were 15 years old and adults were 24 years old on average. The median (IQR) UF concentration among adolescents was 0.48 (0.48) mg/L. Approximately 74% of adolescents and 70% of adults had DF with varying degrees of severity (ranging from very mild to severe). Each 1 mg/L increase in UF was associated with an approximately 5 mL/min/1.73 m² lower eGFR among adolescents (B = -4.73, 95% CI: -8.35, -1.12, p = 0.010). Higher UF was also associated with higher serum uric acid (mg/dl) (B = 0.17, 95% CI: 0.01, 0.33, p = 0.040) among adolescents. DF was associated with lower eGFR among adolescents (B = -3.72, 95% CI: -7.10, -0.33, p = 0.031) and adults (B = -3.90, 95% CI: -6.49, -1.31, p = 0.003). In addition, having DF was negatively associated with BUN among adolescents (B = -0.83, 95% CI: -1.44, -0.22, p = 0.007). No other significant associations were observed for liver markers. Chronic fluoride exposure during tooth development and recent fluoride exposure in adolescence are cross-sectionally associated with a lower rate of kidney filtration among adolescents and young adults in the US. Prospective US-based studies are needed to determine whether these associations are causal.

Early life fluoride exposure and sleep in children

Annals of Epidemiology · 2025-09-01

Urinary Fluoride Levels Among Youth in the National Health and Nutrition Examination Survey (NHANES) 2015–2016: Potential Differences According to Race

Nutrients · 2025-01-16 · 6 citations

Background/Objectives: Urinary fluoride (UF) is the most well-established biomarker for fluoride exposure, and understanding its distribution can inform risk assessment for potential adverse systemic health effects. To our knowledge, this study is the first to report distributions of UF among youth according to sociodemographic factors in a nationally representative United States (US) sample. Methods: The study included 1191 children aged 6-11 years and 1217 adolescents aged 12-19 years from the National Health and Nutrition Examination Survey (NHANES) 2015–2016. We examined UF according to sociodemographic variables as well as Spearman correlations between UF and plasma fluoride. Survey-weighted quantile regression examined associations between tap water fluoride and UF levels adjusted for covariates. Results: The average age of participants was 12.5 years. The median (IQR) UF and water fluoride concentrations were 0.52 (0.50) mg/L and 0.39 (0.54) mg/L, respectively. Children had higher UF levels than adolescents and males had higher UF levels than females. UF differed according to race/ethnicity among both children and adolescents. Specifically, non-Hispanic Black youth tended to have higher UF levels than all participants except for those classified as other race/multiracial. UF and plasma fluoride were moderately correlated for children and adolescents. Higher water fluoride levels were associated with higher UF levels, and the magnitudes of association were larger at higher quantiles of UF (β = 0.14, p &lt; 0.001; β = 0.20, p&lt; 0.001 at the 25th and 50th quantiles, respectively). The magnitude of association between water fluoride and UF was the largest for non-Hispanic Black participants (predictive margin = 0.3, p &lt; 0.001). Conclusions: Non-Hispanic Black youth in the US may have greater fluoride exposure and receive more of their fluoride intake from tap water than youth of other races/ethnicities. Factors contributing to potential racial/ethnic disparities in fluoride exposure within the US warrant further investigation so that they can be mitigated to reduce the potential for harm.

Platelet parameters in preeclampsia: comparing rotational thromboelastometry and platelet aggregometry with standard laboratory tests

International Journal of Obstetric Anesthesia · 2025-12-06

Urinary Fluoride Levels Among Youth in NHANES 2015-2016: Potential Differences According to Race

2024-10-07

Urinary fluoride (UF) is the most well-established biomarker for fluoride exposure, and understanding its distribution can inform risk assessment for potential adverse systemic health effects. To our knowledge, this study is the first to report distributions of UF in a nationally representative United States (US) sample. The study included 1,191 children and 1,217 adolescents from NHANES 2015-2016. We examined UF according to sociodemographic variables and observed Spearman correlations between UF and plasma fluoride. Survey-weighted quantile regression examined associations between tap water fluoride and UF levels adjusted for covariates. The average age of participants was 12.5 years. The median (IQR) UF and water fluoride concentrations were 0.52 (0.50) mg/L and 0.39 (0.54) mg/L, respectively. Children had higher UF levels than adolescents and males had higher UF levels than females. UF differed according to race/ethnicity among both children and adolescents. Specifically, non-Hispanic Black youth tended to have higher UF levels than all participants except for those classified as other race/multiracial. UF and plasma fluoride were moderately correlated for children and adolescents. Higher water fluoride levels were associated with higher UF levels and the magnitudes of association were larger at higher quantiles of UF (β=0.14, p &lt;0.00; β=0.20, p&lt; 0.001 at the 25th and 50th quantiles respectively). The magnitude of association between water fluoride and UF was the largest for non-Hispanic Black participants (predictive margin=0.3, p &lt;0.001). Non-Hispanic Black youth in the US may have greater fluoride exposure and receive more of their fluoride intake from tap water than youth of other races/ethnicities.

Maternal Urinary Fluoride and Child Neurobehavior at Age 36 Months

JAMA Network Open · 2024-05-20 · 23 citations

Importance: Recent studies in Canadian and Mexican populations suggest an association of higher prenatal fluoride exposure with poorer neurobehavioral development, but whether this association holds for US-based populations is unknown. Objective: To examine associations of third trimester maternal urinary fluoride (MUF) with child neurobehavior at age 3 years in the US. Design, Setting, and Participants: This prospective cohort study utilized urine samples archived from 2017 to 2020 and neurobehavioral data assessed from 2020 to 2023 from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, which consisted of predominately Hispanic women residing in Los Angeles, California. Cohort eligibility criteria at recruitment included being 18 years of age or older, less than 30 weeks' gestation, and a fluent English or Spanish speaker. Exclusion criteria included having a disability preventing participation or provision of informed consent, being HIV positive or incarcerated, and having a multiple gestation pregnancy. There were 263 mother-child pairs who completed the 3-year study visit. In this analysis, women who reported prenatal smoking were excluded. Data analysis was conducted from October 2022 to March 2024. Exposure: Specific gravity-adjusted MUF (MUFSG), a biomarker of prenatal fluoride exposure. Main Outcomes and Measures: Neurobehavior was quantified using the Preschool Child Behavior Checklist (CBCL), which included composite scores for Total Problems, Internalizing Problems, and Externalizing Problems. CBCL composite T scores range from 28 to 100. T scores from 60 to 63 are in the borderline clinical range, whereas scores above 63 are in the clinical range. Linear and logistic regression models adjusted for covariates were conducted. Results: A total of 229 mother-child pairs (mean [SD] maternal age, 29.45 [5.67] years; 116 female children [50.7%] and 113 male children [49.3%]) who had MUFSG measured were included in the study. Median (IQR) MUFSG was 0.76 (0.51-1.19) mg/L, and 32 participants (14.0%) had a Total Problems T score in the borderline clinical or clinical range. A 1-IQR (0.68 mg/L) increase in MUFSG was associated with nearly double the odds of the Total Problems T score being in the borderline clinical or clinical range (odds ratio, 1.83; 95% CI, 1.17-2.86; P = .008), as well as with a 2.29-point increase in T score for the Internalizing Problems composite (B = 2.29; 95% CI, 0.47-4.11; P = .01) and a 2.14-point increase in T score for the Total Problems composite (B = 2.14; 95% CI, 0.29-3.98; P = .02). Conclusions and Relevance: In this prospective cohort study of mother-child pairs in Los Angeles, California, prenatal fluoride exposure was associated with increased neurobehavioral problems. These findings suggest that there may be a need to establish recommendations for limiting fluoride exposure during the prenatal period.

The Potential Systemic Role of Diet in Dental Caries Development and Arrest: A Narrative Review

Nutrients · 2024-05-13 · 19 citations

Current conceptualizations of dental caries etiology center primarily on the local role of sugar, starch, or other fermentable carbohydrates on tooth enamel demineralization-a well-established and empirically supported mechanism. However, in addition to this mechanism, studies dating back to the early 1900s point to an important systemic role of diet and nutrition, particularly from pasture-raised animal-source foods (ASF), in dental caries etiology and arrest. Findings from animal and human studies suggest that adherence to a diet high in calcium, phosphorus, fat-soluble vitamins A and D, and antioxidant vitamin C, as well as low in phytates, may contribute to arrest and reversal of dental caries, particularly among children. Furthermore, findings from observational and experimental studies of humans across the life-course suggest that fat-soluble vitamins A, D, and K2 may interact to protect against dental caries progression, even within a diet that regularly contains sugar. While these historic studies have not been revisited in decades, we emphasize the need for them to be reinvestigated and contextualized in the 21st century. Specifically, methodologically rigorous studies are needed to reinvestigate whether historical knowledge of systemic impacts of nutrition on dental health can help to inform current conceptualizations of dental caries etiology, prevention, and arrest.