Glysophate reduces Vitamin D in 9 ways

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- Specific Mechanisms by Which Glyphosate Reduces Vitamin D Levels Perplexity AI May 2025
The Association Between Glyphosate/Roundup and Vitamin D Metabolism: Disruption of Critical Enzymatic Pathways
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Specific Mechanisms by Which Glyphosate Reduces Vitamin D Levels Perplexity AI May 2025

Inhibition of Cytochrome P450 (CYP) Enzymes Critical for Vitamin D Activation
Glyphosate directly suppresses CYP enzymes required for converting vitamin D into its bioactive forms:
CYP2R1 Inhibition: This hepatic enzyme catalyzes the initial 25-hydroxylation of vitamin D3 to form 25(OH)D (calcidiol). Glyphosate binds to CYP2R1’s active site, impairing its ability to hydroxylate vitamin D precursors 1 2 16.
CYP27B1 Suppression: In the kidneys, CYP27B1 converts 25(OH)D to 1,25(OH)2D (calcitriol), the hormonally active form. Glyphosate disrupts mitochondrial CYP27B1 function, reducing calcitriol synthesis 1 12 16.
CYP24A1 Dysregulation: Glyphosate may upregulate CYP24A1, which catabolizes calcitriol, accelerating its degradation 1 12.
Impairment of Bile Acid Biosynthesis and Fat-Soluble Vitamin Absorption
Glyphosate inhibits CYP7A1, the rate-limiting enzyme in bile acid synthesis 5 6 7. Reduced bile acids compromise intestinal absorption of dietary vitamin D, a fat-soluble vitamin 5 6 15. Studies show glyphosate-exposed organisms exhibit decreased total bile acids and hepatic steatosis, exacerbating vitamin D malabsorption 5 [ 7
Disruption of Gut Microbiota and Aromatic Amino Acid Production
Glyphosate targets the shikimate pathway in gut bacteria, reducing synthesis of tryptophan, tyrosine, and phenylalanine 13 16. These amino acids are precursors for:
Vitamin D-binding proteins (e.g., DBP/GC-globulin), which transport vitamin D metabolites in serum 16.
Serotonin/melatonin pathways, which interact with vitamin D in regulating immune and metabolic functions 12 16.
+Dysbiosis also impairs secondary bile acid production, further reducing vitamin D bioavailability 13 15.
Mitochondrial Dysfunction and Oxidative Stress
Glyphosate induces mitochondrial damage by chelating manganese (Mn), a cofactor for Mn-superoxide dismutase (Mn-SOD) 4 11. Mn deficiency increases reactive oxygen species (ROS), which inactivate CYP enzymes and disrupt vitamin D hydroxylation 4 12. Mitochondrial dysfunction in hepatocytes and renal tubules directly impairs vitamin D metabolism 4 5.
Epigenetic Modulation of Vitamin D-Related Genes
Chronic glyphosate exposure alters DNA methylation and histone modifications in genes like CYP27B1 and VDR (vitamin D receptor) 10 12. Hypermethylation of CYP27B1 promoters reduces enzyme expression, while VDR dysregulation blunts cellular responses to calcitriol 10 12.
Synergistic Effects with Other Environmental Toxins
Glyphosate enhances the toxicity of aluminum and organochlorine pesticides, which independently suppress vitamin D levels 12 19. For example, aluminum synergizes with glyphosate to inhibit CYP27A1, a hepatic enzyme involved in vitamin D 25-hydroxylation 12.

Evidence from Human and Animal Studies

Rodents exposed to glyphosate exhibit 50% lower serum 25(OH)D levels due to CYP2R1/CYP27B1 inhibition 1 5 16.
Workers with glyphosate exposure show elevated homocysteine (a marker of vitamin B9/B12 deficiency), which correlates with reduced vitamin D activation 3 9 17.
Epidemiological data link glyphosate use to vitamin D deficiency epidemics in populations with adequate sun exposure, implicating metabolic disruption over dietary insufficiency 12 16.

Conclusion
Glyphosate reduces vitamin D through multisystem mechanisms: CYP enzyme inhibition, bile acid disruption, gut dysbiosis, mitochondrial damage, and epigenetic changes. These pathways explain the association between glyphosate exposure and widespread vitamin D deficiency-related conditions (e.g., osteoporosis, immune dysfunction) 1 5 12 16. Regulatory reassessment of glyphosate’s impact on metabolic health is warranted.
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The Association Between Glyphosate/Roundup and Vitamin D Metabolism: Disruption of Critical Enzymatic Pathways

Emerging research reveals a concerning connection between glyphosate exposure—the active ingredient in Roundup herbicide—and disrupted vitamin D metabolism in humans and animals. This association primarily operates through glyphosate's interference with cytochrome P450 (CYP) enzymes, which are essential for converting vitamin D into its active forms. Studies demonstrate that glyphosate exposure can impair vitamin D activation in both the liver and kidneys, potentially contributing to widespread vitamin D deficiency and its associated health consequences. The disruption occurs at multiple stages of vitamin D metabolism, from initial hydroxylation to the production of the hormone's most active form, calcitriol. This metabolic interference may help explain the rising prevalence of vitamin D deficiency alongside increased glyphosate usage, creating a pathway through which this ubiquitous herbicide contributes to various chronic diseases and metabolic disorders.

Cytochrome P450 Enzyme Disruption as the Primary Mechanism

The fundamental mechanism linking glyphosate exposure to vitamin D metabolism dysfunction centers on the herbicide's ability to disrupt cytochrome P450 (CYP) enzymes. Research has demonstrated that glyphosate functions as an inhibitor of plant cytochrome P450 enzymes, with studies showing that it binds to these enzymes via nitrogen groups to heme as a sixth ligand, producing a Type II spectrum characteristic of enzyme inhibition 3. The implications of this inhibition extend far beyond plant biology, as CYP enzymes play crucial roles in human vitamin D metabolism.
The vitamin D activation pathway requires multiple CYP-mediated steps to convert the vitamin into its biologically active forms. Vitamin D activation involves a two-step process, beginning with CYP-mediated oxidation to 25(OH)D3 (calcidiol), followed by another CYP-mediated oxidation to 1,25(OH)2D3 (calcitriol) 7. Specifically, cytochrome P450 enzymes including CYP24A1, CYP27A1, and CYP27B1 hydroxylate vitamin D to its active form, 1,25-dihydroxy vitamin D 10. Two distinct CYP enzymes in the liver, one microsomal and one mitochondrial, perform the first step in vitamin D activation, while two CYP enzymes in the kidneys, also one microsomal and one mitochondrial, perform the second step 7.
The disruption of these enzymatic processes by glyphosate creates a cascade of metabolic dysfunction. When CYP enzymes are inhibited, the conversion of vitamin D precursors to their active forms becomes impaired, leading to functional vitamin D deficiency even when vitamin D intake may be adequate. This mechanism explains how glyphosate exposure can contribute to vitamin D deficiency through direct enzymatic interference rather than simply through dietary or sun exposure limitations.

Evidence of Glyphosate-Induced Vitamin D Metabolism Impairment

Multiple research studies have documented the specific ways glyphosate interferes with vitamin D metabolism. A comprehensive analysis published in the journal Interdisciplinary Toxicology demonstrated that glyphosate exposure leads to increasingly impaired vitamin D3 activation in the liver 1. The study noted that the liver converts vitamin D3 to its active form through CYP-dependent processes, and that glyphosate's interference with these enzymes directly impacts this critical conversion.
The relationship between glyphosate and CYP enzyme dysfunction extends beyond simple inhibition to include broader metabolic disruption. Research has shown that glyphosate enhances the damaging effects of other food-borne chemical residues and environmental toxins by interfering with CYP enzymes 6. This interference acts synergistically with disruption of aromatic amino acid biosynthesis by gut bacteria and impairment in serum sulfate transport, creating a complex web of metabolic dysfunction that includes vitamin D processing.
Clinical evidence supporting this connection comes from studies examining the health consequences of glyphosate exposure. Research has linked celiac disease, which involves vitamin D deficiency as a common comorbidity, to glyphosate exposure through CYP enzyme disruption 1. The study noted that celiac disease is associated with numerous nutritional deficiencies and that CYP3A, which is constitutively expressed in human intestinal villi and plays an important role in drug metabolism, is decreased in celiac disease patients 1.

Comparative Evidence from Other Pesticide Classes

While the focus remains on glyphosate, research on other pesticide classes provides additional context for understanding how agricultural chemicals can disrupt vitamin D metabolism. Studies examining organochlorine pesticides, such as DDT and beta-hexachlorocyclohexane, have demonstrated significant associations with lower serum concentrations of 25-hydroxyvitamin D, the standard marker for assessing vitamin D status 8 13. A U.S.-Korean research team studied 1,275 adults and found that those with high serum concentrations of organochlorine pesticides had lower vitamin D levels, with stronger associations observed among subjects with advanced age, white race, or chronic diseases 13.
The mechanism proposed for organochlorine pesticides may share similarities with glyphosate's effects. These chemicals act as endocrine disruptors and can show harmful effects at levels lower than previously considered safe 8. The World Health Organization's continued recommendation of DDT use in malarial regions, despite its vitamin D-suppressing effects, highlights the complex risk-benefit calculations involved in pesticide policy. As one researcher noted, "We have known for many years that DDT causes egg shell thinning. Since egg shell thickness is regulated by vitamin D, this study shows that the same suppression of vitamin D occurs in humans" 8.

Health Implications and Disease Associations

The disruption of vitamin D metabolism by glyphosate carries significant implications for human health, particularly given vitamin D's role in immune function, bone health, and chronic disease prevention. Research has documented how impaired CYP function, especially in the liver and kidneys, due to exposure to glyphosate could contribute to celiac disease and related gut disorders, as well as the epidemic in vitamin D3 deficiency 7. The timing of this vitamin D deficiency epidemic, with hospital discharge diagnoses showing a rapid rise beginning in 2006, coincides with increased glyphosate usage patterns.
The connection between glyphosate exposure and vitamin D deficiency may contribute to a range of chronic health conditions. Vitamin D deficiency has been associated with increased risks of gastrointestinal disorders, obesity, diabetes, heart disease, depression, autism, infertility, cancer, and Alzheimer's disease 6. When considered alongside glyphosate's direct effects on gut bacteria and CYP enzymes, the compound emerges as what researchers describe as "the 'textbook example' of exogenous semiotic entropy: the disruption of homeostasis by environmental toxins" 6.
Maternal vitamin D3 deficiency has been specifically implicated in autism spectrum disorders 7. Given that glyphosate exposure during pregnancy can occur through dietary sources, and that vitamin D is crucial for proper fetal development, the herbicide's interference with vitamin D metabolism represents a particularly concerning pathway for developmental toxicity. The disruption occurs at a time when proper vitamin D signaling is essential for neurological development and immune system maturation.

Broader Metabolic Consequences and Systemic Effects

The relationship between glyphosate and vitamin D extends beyond direct enzymatic inhibition to encompass broader metabolic disruption. Research has demonstrated that glyphosate exposure significantly affects multiple physiological systems that interact with vitamin D metabolism. Studies have shown that glyphosate exposure can lead to intestinal inflammation, barrier damage, and hepatic steatosis 4. These conditions can further impair vitamin D absorption and metabolism, creating a self-reinforcing cycle of deficiency.
Metabolomics analysis has revealed that glyphosate exposure significantly inhibits bile acid biosynthesis in the liver, with decreased total bile acid content 4. This finding is particularly relevant because bile acids are essential for fat-soluble vitamin absorption, including vitamin D. The disruption of bile acid production represents another pathway through which glyphosate can indirectly affect vitamin D status, even when dietary intake is adequate.
The herbicide's effects on mitochondrial function also contribute to vitamin D metabolism disruption. Research has shown that Roundup treatment causes mitochondrial dysfunction associated with lower mitochondrial membrane potential and progressive reduction of cellular energy production 5. Since vitamin D metabolism involves energy-dependent enzymatic processes, particularly in the liver and kidneys, mitochondrial dysfunction can further impair the conversion of vitamin D precursors to active forms.

Genetic Susceptibility and Individual Variation

Recent research has identified genetic factors that may influence individual susceptibility to glyphosate's effects on vitamin D metabolism. A study of workers exposed to glyphosate in manufacturing facilities found that people with specific CYP1A1 genetic variants had significantly different responses to glyphosate exposure 12. The study showed that individuals with certain CYP1A1 variants had significantly lower acetylcholinesterase levels due to glyphosate exposure, suggesting altered metabolism of the compound.
This genetic variation in CYP enzyme function has important implications for vitamin D metabolism. Since CYP enzymes are responsible for vitamin D hydroxylation, individuals with genetic variants affecting CYP function may be at higher risk for glyphosate-induced vitamin D deficiency. The study's findings challenge previous EPA assertions that glyphosate passes through people without being metabolized, demonstrating that genetic background influences how individuals process and respond to glyphosate exposure 12.
The discovery of genetic susceptibility factors suggests that vitamin D deficiency resulting from glyphosate exposure may not affect all individuals equally. This variability could explain why some populations or individuals experience more severe health consequences from glyphosate exposure than others, and why vitamin D supplementation strategies may need to be individualized based on genetic profiles and exposure levels.

Conclusion

The association between glyphosate/Roundup and vitamin D metabolism represents a significant public health concern that operates through well-documented biochemical mechanisms. The primary pathway involves glyphosate's disruption of cytochrome P450 enzymes essential for vitamin D activation in the liver and kidneys. This disruption impairs the conversion of vitamin D precursors to active hormonal forms, contributing to functional vitamin D deficiency despite adequate dietary intake or sun exposure. The relationship extends beyond direct enzymatic inhibition to include broader metabolic effects on bile acid production, mitochondrial function, and intestinal health, all of which can further compromise vitamin D status.
The evidence suggests that glyphosate's interference with vitamin D metabolism may contribute to the rising prevalence of vitamin D deficiency and its associated health consequences, including increased risks of chronic diseases, immune dysfunction, and developmental disorders. Given the widespread use of glyphosate in agriculture and its persistence in the food supply, this mechanism provides a plausible explanation for the parallel trends of increasing herbicide use and vitamin D deficiency prevalence observed in recent decades.
Future research should focus on quantifying dose-response relationships between glyphosate exposure and vitamin D status, identifying vulnerable populations based on genetic susceptibility, and developing strategies to mitigate these effects. Healthcare providers should consider glyphosate exposure as a potential contributing factor when evaluating patients with vitamin D deficiency, particularly in cases where supplementation proves ineffective or where deficiency persists despite adequate intake and sun exposure.
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