- The Association Between Glycine and Vitamin D: A Comprehensive Analysis – Perplexity AI April 2025
- Glycine's Effect on Vitamin D Status
- Vitamin D's Effect on Glycine Metabolism
- Molecular Mechanisms Connecting Glycine and Vitamin D
- Clinical Implications
- Conclusion
- Review of Glycine health problems and supplements at ConsumerLab - April 2025 (free access for 1 week)
- Glycine is essential for the synthesis of glutathione, the master anti-oxidant
Health Problems Associated with Low Glycine
Summary
| Health Problem | Association with Low Glycine |
| Obesity, T2DM, NAFLD | Strongly associated, may worsen risk |
| Depression, Anxiety, Sleep Disorders | Linked to neurotransmitter imbalance |
| Cognitive Impairment, Neurodegeneration | Possible contribution |
| Muscle Weakness, Fatigue | Impaired creatine synthesis |
| Inflammation | Associated with low-grade inflammation |
| Hypothyroidism | Often observed in low glycine states |
| Gastrointestinal Disorders | Reduced protection against ulcers |
| Vascular Disease | Increased cardiovascular risk |
| Poor Recovery After Stroke | Loss of neuroprotection |
Low glycine levels have been linked to a range of health problems affecting metabolic, neurological, muscular, and psychological health. Here’s a summary of the main issues associated with glycine deficiency:
Metabolic Disorders
- Low plasma glycine is consistently associated with obesity, type 2 diabetes (T2DM), and non-alcoholic fatty liver disease (NAFLD) 1 3 6 8. Glycine plays a crucial role in regulating glucose metabolism and insulin sensitivity, so deficiency may contribute to the development or progression of these metabolic conditions 1 3 6.
Mood and Cognitive Disorders
- Glycine acts as an inhibitory neurotransmitter in the central nervous system. Deficiency has been linked to mood disorders, such as depression and anxiety, as well as cognitive impairments and sleep disturbances 1 8. There is also evidence suggesting that low glycine may contribute to the development of neurodegenerative diseases like Alzheimer's and Parkinson's by disrupting neurotransmitter balance and increasing oxidative stress in the brain 1.
Muscle and Energy Issues
- Glycine is essential for creatine synthesis, which is vital for energy production in muscle cells. Low glycine can impair creatine synthesis, leading to reduced energy availability, increased fatigue, muscle wasting, impaired recovery after exercise, and stunted growth in children and adolescents 1 7.
Impaired Antioxidant Defense
- Glycine is a precursor for glutathione, a key antioxidant. Deficiency can reduce glutathione production, making cells more susceptible to oxidative stress and contributing to feelings of weakness and exhaustion 1.
Inflammation
- Low glycine plasma levels are associated with low-grade inflammation. Glycine has anti-inflammatory and neuroprotective effects, and its deficiency can exacerbate inflammatory processes, particularly in metabolic and vascular diseases 6.
Gastrointestinal and Vascular Health
- Glycine plays a protective role in the gastrointestinal tract, helping to prevent gastric ulcers and inflammation. Deficiency may increase susceptibility to these issues 1. Glycine also supports vascular health, and lower levels are linked to higher cardiovascular risk 1 4.
Other Associations
- Hypothyroidism: Low glycine levels are often seen in hypothyroidism, indicating a possible link between glycine and thyroid function 1 8.
- Stroke: Some studies suggest that low glycine may be associated with worse outcomes after ischemic stroke, due to its neuroprotective properties 6.
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Maintaining adequate glycine levels is important for metabolic, neurological, muscular, and psychological health. Glycine deficiency can be addressed through dietary sources, supplements, or collagen-rich foods, but it is essential to consult a healthcare professional for proper assessment and management 1 7 8.
Citations:
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The Association Between Glycine and Vitamin D: A Comprehensive Analysis – Perplexity AI April 2025
Glycine, the simplest amino acid in human physiology, and vitamin D, a crucial fat-soluble vitamin, both play fundamental roles in human metabolism. Recent research has uncovered several interesting associations between these two important biological compounds. This report examines the evidence for biochemical, metabolic, and clinical relationships between glycine and vitamin D.
Glycine's Effect on Vitamin D Status
Protective Effects in Liver Disease
Research has demonstrated a potentially protective relationship between glycine and vitamin D status, particularly in conditions affecting liver function. In a study examining bile duct ligation (BDL)-induced liver injury, glycine treatment showed remarkable effects on vitamin D levels. Animals with BDL typically experienced a significant decrease in serum 25-hydroxyvitamin D (25OHD) concentrations, approximately 50% lower than control groups 1. However, administration of glycine (but not other amino acids like alanine, serine, or tyrosine) effectively blunted this reduction in vitamin D levels 1.
The protective mechanism appears to work through multiple pathways. Glycine treatment ameliorated liver damage as indicated by improved serum AST and ALT levels, reduced hepatic caspase 3 activities (a marker of apoptosis), and decreased oxidative stress markers 1. The concentrations of 25OHD were found to be negatively associated with ischemia-modified albumin and caspase 3, suggesting that glycine's protective effect on vitamin D status may be linked to its ability to reduce oxidative stress and apoptosis 1.
Metabolic Interrelationships
Studies examining amino acid metabolism disorders in neonates have revealed significant correlations between glycine and vitamin D levels. Research has found that children with amino acid metabolism disorders typically have lower plasma glycine and vitamin D3 levels compared to healthy controls [https://archivespsy.com/menu-script/index.php/ACF/article/download/1211/1691|10]. More importantly, statistical analysis has demonstrated a notable positive correlation between plasma vitamin D levels and glycine levels in these patients 8 10.
Vitamin D's Effect on Glycine Metabolism
Alterations in Cellular Glycine Concentrations
While glycine can affect vitamin D status, the relationship appears bidirectional. Metabolomic analyses have revealed that vitamin D treatment can influence glycine metabolism in various cellular models. In HEK293T cells, vitamin D administration induced significant metabolic alterations, including a marked decrease in intracellular glycine concentration 15 16.
These vitamin D-induced reductions in glycine appear to be part of a broader metabolic reprogramming effect, which also impacts other amino acids and metabolites including sorbitol, glutamate, and guanine 16. Researchers propose this metabolic reprogramming may protect cells from oxidative stress and help maintain a highly proliferative phenotype 16.
Historical research has also noted that vitamin D3 can significantly decrease the levels of glycine in certain experimental models 9. This aligns with more recent metabolomic studies suggesting vitamin D may regulate amino acid metabolism including glycine.
Molecular Mechanisms Connecting Glycine and Vitamin D
Vitamin D Receptor (VDR) Signaling
The vitamin D receptor (VDR) is a nuclear receptor that mediates most biological actions of vitamin D. When activated by the biologically active form of vitamin D (1,25-dihydroxyvitamin D), VDR forms a heterodimer with the retinoid-X receptor and regulates gene expression 2 11. Some laboratory studies investigating VDR signaling use glycine for technical procedures during cell fixation 6, though this represents a laboratory application rather than a physiological relationship.
Enzymatic Relationships in Vitamin D Metabolism
The metabolism of vitamin D requires several enzymatic steps. The primary activation pathway involves 25-hydroxylation (primarily by CYP2R1) followed by 1α-hydroxylation (by CYP27B1) to form the active 1,25-dihydroxyvitamin D 12 13. Mutations in these enzymes can lead to disorders such as vitamin D-dependent rickets 4 5.
While glycine itself is not directly involved in these enzymatic reactions, research has identified interesting connections. For example, a study found that a single A326G mutation (substituting alanine with glycine at position 326) in the CYP24A1 enzyme dramatically changes its regioselectivity from a 24-hydroxylase to a 23-hydroxylase, altering vitamin D metabolism 15. This demonstrates how even small amino acid changes involving glycine can significantly impact vitamin D metabolic pathways.
Clinical Implications
Considerations for Supplementation
The interconnection between glycine and vitamin D may have practical implications for supplementation strategies. Studies examining magnesium glycinate (a form of magnesium bound to glycine) and vitamin D3 supplementation suggest they can be safely and beneficially taken together 3. Magnesium is essential for vitamin D activation, as "all of the enzymes that metabolize vitamin D seem to require magnesium" 3. Taking them together may be more effective at correcting vitamin D levels than taking vitamin D alone 3.
Potential Applications in Metabolic Disorders
Understanding the relationship between glycine and vitamin D may be particularly relevant for treating metabolic disorders. In neonates with amino acid metabolism disorders, studies have shown that both glycine and vitamin D levels are significantly lower than in healthy controls 8 10. The positive correlation between vitamin D and glycine levels suggests potential therapeutic approaches targeting both compounds simultaneously 10.
Conclusion
The evidence indicates several meaningful associations between glycine and vitamin D across multiple biological contexts. Glycine appears to help maintain vitamin D status in certain liver conditions, while vitamin D can influence glycine metabolism as part of broader metabolic regulation. The positive correlation observed between glycine and vitamin D levels in metabolic disorders points to a physiologically significant relationship.
These findings suggest potential clinical applications, particularly in treating conditions characterized by disturbances in both vitamin D status and amino acid metabolism. Future research should further explore the molecular mechanisms underlying these associations and their therapeutic implications.
The bidirectional relationship between glycine and vitamin D represents an intriguing area of nutritional biochemistry that merits continued investigation, especially as both compounds play crucial roles in human health and disease prevention.
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Review of Glycine health problems and supplements at ConsumerLab - April 2025 (free access for 1 week)
Glycine is essential for the synthesis of glutathione, the master anti-oxidant
VitaminDWiki - Glutathione and Vitamin D synergism - many studies