Benoit Follin-Arbelet, Bjørn Moum. Fluoride: A Risk Factor for Inflammatory Bowel Disease? Scand J Gastroenterol, 51 (9), 1019-24, Sep 2016
Although the association between inflammatory bowel disease (IBD) and oral hygiene has been noticed before, there has been little research on prolonged fluoride exposure as a possible risk factor. In the presented cases, exposure to fluoride seems indirectly associated with higher incidence of IBD. Fluoride toxicology and epidemiology documents frequent unspecific chronic gastrointestinal symptoms and intestinal inflammation. Efflux genes that confer resistance to environmental fluoride may select for IBD associated gut microbiota and therefore be involved in the pathogenesis. Together these multidisciplinary results argue for further investigation on the hypothesis of fluoride as a risk factor for IBD.
Tetsuo Nakamoto, H Ralph Rawls. Fluoride Exposure in Early Life as the Possible Root Cause of Disease In Later Life, The Journal of clinical pediatric dentistry. 42 (5), 325-330, 2018 doi: 10.17796/1053-4625-42.5.1
Fluoride, one of the most celebrated ingredients for the prevention of dental caries in the 20th century, has also been controversial for its use in dentifrices and other applications. In the current review, we have concentrated primarily on early-life exposure to fluoride and how it may affect the various organs. The most recent controversial aspects of fluoride are related to toxicity of the developing brain and how it may possibly result in the decrease of intelligence quotient (IQ), autism, and calcification of the pineal gland. In addition, it has been reported to have possible effects on bone and thyroid glands. If nutritional stress is applied during a critical period of growth and development, the organ(s) and/or body will never recover once they pass through the critical period. For example, if animals are force-fed during experiments, they will simply get fat but never reach the normal size. Although early-life fluoride exposure causing fluorosis is well reported in the literature, the dental profession considers it primarily as an esthetic rather than a serious systemic problem. In the current review, we wanted to raise the possibility of future disease as a result of early-life exposure to fluoride. It is not currently known how fluoride will become a cause of future disease. Studies of other nutritional factors have shown that the effects of early nutritional stress are a cause of disease in later life.
Goschorska M, Baranowska-Bosiacka I, Gutowska I, Metryka E, Skórka-Majewicz M, Chlubek D. Potential Role of Fluoride in the Etiopathogenesis of Alzheimer’s Disease. Int J Mol Sci. 2018 Dec 9;19(12). pii: E3965. doi: 10.3390/ijms19123965.
The etiopathogenesis of Alzheimer’s disease has not been fully explained. Now, the disease is widely attributed both to genetic and environmental factors. It is believed that only a small percentage of new AD cases result solely from genetic mutations, with most cases attributed to environmental factors or to the interaction of environmental factors with preexistent genetic determinants. Fluoride is widespread in the environment and it easily crosses the blood⁻brain barrier. In the brain fluoride affects cellular energy metabolism, synthesis of inflammatory factors, neurotransmitter metabolism, microglial activation, and the expression of proteins involved in neuronal maturation. Finally, and of specific importance to its role in Alzheimer’s disease, studies report fluoride-induced apoptosis and inflammation within the central nervous system. This review attempts to elucidate the potential relationship between the effects of fluoride exposure and the pathogenesis of Alzheimer’s disease. We describe the impact of fluoride-induced oxidative stress and inflammation in the pathogenesis of AD and demonstrate a role for apoptosis in disease progression, as well as a mechanism for its initiation by fluoride. The influence of fluoride on processes of AD initiation and progression is complex and warrants further investigation, especially considering growing environmental fluoride pollution.
Sharma D, Singh A, Verma K, Paliwal S, Sharma S, Dwivedi J. Fluoride: A review of pre-clinical and clinical studies. Environmental toxicology and pharmacology. 2017 Dec;56:297-313. doi: 10.1016/j.etap.2017.10.008.
Fluoride is ubiquitous in environment and profound in bones, teeth and calcified tissues of human body. Fluoride has been the topic of regular discussion and investigations. Besides its toxicity, fluoride has also been examined for its beneficial effects like prevention and treatment of tooth decay, microbial infection, inflammation, cancer, occurrence of renal stone and many more. Since last many decades, several efforts have been made at pre-clinical and clinical level to understand role of fluoride in biological system. The present review gives a brief account of prevalence, sources of fluoride toxicity and pre-clinical and clinical studies carried out on effects of fluoride in last six decades.
Shenoy PS, Sen U, Kapoor S, Ranade AV, Chowdhury CR, Bose B. Sodium fluoride induced skeletal muscle changes: Degradation of proteins and signaling mechanism. Environmental Pollution 2019 Jan;244:534-548. doi: 10.1016/j.envpol.2018.10.034. Epub 2018 Oct 10.
Fluoride is a well-known compound for its usefulness in healing dental caries. Similarly, fluoride is also known for its toxicity to various tissues in animals and humans. It causes skeletal fluorosis leading to osteoporosis of the bones. We hypothesized that when bones are affected by fluoride, the skeletal muscles are also likely to be affected by underlying molecular events involving myogenic differentiation. Murine myoblasts C2C12 were cultured in differentiation media with or without NaF (1 ppm-5 ppm) for four days. The effects of NaF on myoblasts and myotubes when exposed to low (1.5 ppm) and high concentration (5 ppm) were assessed based on the proliferation, alteration in gene expression, ROS production, and production of inflammatory cytokines. Changes based on morphology, multinucleated myotube formation, expression of MyHC1 and signaling pathways were also investigated. Concentrations of NaF tested had no effects on cell viability. NaF at low concentration (1.5 ppm) caused myoblast proliferation and when subjected to myogenic differentiation it induced hypertrophy of the myotubes by activating the IGF-1/AKT pathway. NaF at higher concentration (5 ppm), significantly inhibited myotube formation, increased skeletal muscle catabolism, generated reactive oxygen species (ROS) and inflammatory cytokines (TNF-α and IL-6) in C2C12 cells. NaF also enhanced the production of muscle atrophy-related genes, myostatin, and atrogin-1. The data suggest that NaF at low concentration can be used as muscle enhancing factor (hypertrophy), and at higher concentration, it accelerates skeletal muscle atrophy by activating the ubiquitin-proteosome pathway.
Dharmaratne RW. Exploring the role of excess fluoride in chronic kidney disease: A review. Hum Exp Toxicol. 2018 Nov 25:960327118814161. doi: 10.1177/0960327118814161.
This review covers nearly 100 years of studies on the toxicity of fluoride on human and animal kidneys. These studies reveal that there are direct adverse effects on the kidneys by excess fluoride, leading to kidney damage and dysfunction. With the exception of the pineal gland, the kidney is exposed to higher concentrations of fluoride than all other soft tissues. Therefore, exposure to higher concentrations of fluoride could contribute to kidney damage, ultimately leading to chronic kidney disease (CKD). Among major adverse effects on the kidneys from excessive consumption of fluoride are immediate effects on the tubular area of the kidneys, inhibiting the tubular reabsorption; changes in urinary ion excretion by the kidneys disruption of collagen biosynthesis in the body, causing damages to the kidneys and other organs; and inhibition of kidney enzymes, affecting the functioning of enzyme pathways. This review proposes that there is a direct correlation between CKD and the consumption of excess amounts of fluoride. Studies particularly show immediate adverse effects on the tubular area of human and animal kidneys leading to CKD due to the consumption of excess fluoride. Therefore, it is very important to conduct more investigations on toxicity studies of excess fluoride on the human kidney, including experiments using human kidney enzymes, to study more in depth the impact of excess fluoride on the human kidney. Further, the interference of excess fluoride on collagen synthesis in human body and its effect on human kidney should also be further investigated.
Huan Zuo, Liang Chen, Ming Kong, Lipeng Qiu, Peng Lü, Peng Wu, Yanhua Yang, Keping Chen. Toxic effects of fluoride on organisms. Life Sciences
Volume 198, 1 April 2018, Pages 18-24
Accumulation of excess fluoride in the environment poses serious health risks to plants, animals, and humans. This endangers human health, affects organism growth and development, and negatively impacts the food chain, thereby affecting ecological balance. In recent years, numerous studies focused on the molecular mechanisms associated with fluoride toxicity. These studies have demonstrated that fluoride can induce oxidative stress, regulate intracellular redox homeostasis, and lead to mitochondrial damage, endoplasmic reticulum stress and alter gene expression. This paper reviews the present research on the potential adverse effects of overdose fluoride on various organisms and aims to improve our understanding of fluoride toxicity.