Benzodiazepines, such as Valium, reduce both anxiety and Vitamin D getting to cells

The effect of 7 genes, such as CYP3A4, are not seen by standard vitamin D tests
Associations between Benzodiazepines and Vitamin D
Main Uses of Benzodiazepines
- Additional Notes
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The effect of 7 genes, such as CYP3A4, are not seen by standard vitamin D tests

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Associations between Benzodiazepines and Vitamin D

The relationship between benzodiazepines and vitamin D is complex and multifaceted, involving several distinct mechanisms that affect both calcium homeostasis and vitamin D metabolism.

Nutrient Depletion Effects

Benzodiazepines can cause several nutrient deficiencies that indirectly affect vitamin D function. Specifically, benzodiazepines decrease calcium absorption and increase the metabolism of vitamin D 1. This occurs because anxiety medications (benzodiazepines) decrease calcium absorption by increasing vitamin D metabolism 2. Additionally, using benzodiazepines like Xanax (alprazolam) comes with increased risk of depleting the body of important nutrients such as calcium, vitamin D, melatonin and B vitamins 3.
The mechanism involves Xanax increasing the body's metabolism of vitamin D, a key vitamin needed for proper calcium absorption 3. This increased metabolism means the body breaks down vitamin D more rapidly, potentially leading to functional deficiency even when vitamin D intake appears adequate.

Clinical Evidence from Research Studies

Multiple cross-sectional studies have investigated the relationship between benzodiazepines and vitamin D levels. In a study of Dutch geriatric outpatients, the absence of a significant association with benzodiazepines was also reported in two other cross-sectional studies involving 737 and 589 participants 4. However, in a second cohort of the first study, a significant inverse association was observed in 1,301 participants 4.
A comprehensive literature review noted that whereas a lack of a significant effect of benzodiazepines on vitamin D status has been reported in three cross-sectional studies 5, the evidence remains mixed. One study specifically noted that in the study, there were no associations between baseline and longitudinal measurements of serum vitamin D levels and frequency of benzodiazepines consumption 6.

Calcium Channel Interactions

Benzodiazepines have complex interactions with calcium channels, which may affect vitamin D's role in calcium homeostasis. Research shows that benzodiazepines (BZs) have been shown to modulate voltage-sensitive Ca2+ channels in a number of neuronal and nonneuronal cell types 7. Studies demonstrate that calcium may enhance the anxiolytic activity of diazepam 8, suggesting an interplay between benzodiazepines and calcium metabolism.
In experimental settings, chronic benzodiazepine administration potentiates high voltage-activated calcium currents in hippocampal CA1 neurons 9, indicating that long-term benzodiazepine use may alter calcium channel function in ways that could affect vitamin D-dependent calcium metabolism.

Patients become sensitive to Vit. D supplements

Clinical observations from benzodiazepine patient communities reveal concerning patterns. Vitamin D deficiencies and supplement intolerance are both frequently reported in benzodiazepine patient support groups 10. This suggests that individuals taking benzodiazepines, particularly those experiencing tolerance or withdrawal, may have heightened sensitivity to vitamin D supplementation or difficulty maintaining adequate vitamin D levels.

Lack of Direct Drug Interactions

Despite these metabolic effects, formal drug interaction databases consistently report no interactions were found between various benzodiazepines and vitamin D3 11 12 13 14 15 16. This absence of documented direct interactions in clinical databases indicates that the relationships observed are likely subtle metabolic effects rather than acute pharmacological interactions.

Benzodiazepines activate the CYP3A4 Enzyme System, which deactivates Vitamin D (not measured by standard blood test)

Both benzodiazepines and vitamin D are metabolized through the CYP3A4 enzyme system, though vitamin D does not affect the hepatic drug metabolism of CYP3A4 dependent substrates 17. While CYP3A4 plays a crucial role in vitamin D catabolism because of a much greater level of basal and induced enzyme expression in liver and intestine 18, the interaction appears to be primarily one-directional, with benzodiazepines potentially affecting vitamin D metabolism rather than vitamin D affecting benzodiazepine metabolism.

Clinical Implications

Healthcare providers should be aware of these potential associations, particularly in elderly patients on long-term benzodiazepine therapy who may be at higher risk for vitamin D deficiency. The evidence suggests that providers of health care ought to be alert to the potential of vitamin D depletions induced by medications, especially in elderly people exposed to multiple-drug therapy 5.
Regular monitoring of vitamin D status in patients on chronic benzodiazepine therapy may be warranted, especially given that 24% of females aged 11–18, males aged 19–64, and females aged 65 years and over have a year-round concentration below 25 nmol/L plasma 25(OH)D 5 in the general population, suggesting baseline deficiency rates are already high.
While the direct interactions between benzodiazepines and vitamin D appear to be limited, the indirect effects through altered metabolism and calcium homeostasis represent clinically relevant associations that warrant attention in patient care.
References

Benzodiazepines are a class of medications primarily used to depress the central nervous system, producing calming effects that are helpful in several medical situations.
They are typically prescribed for short-term use due to their risk of dependence and withdrawal.

Main Uses of Benzodiazepines

Anxiety Disorders: Used to relieve symptoms of anxiety and panic disorders, especially when rapid symptom control is needed 1 2 3 4 5.
Insomnia: Prescribed for short-term treatment of sleep disorders by helping people fall asleep or stay asleep 1 2 4 5.
Seizure Disorders: Employed to control or abort seizures and as part of ongoing management of epilepsy 1 6 3 4 5.
Muscle Relaxation: Useful for relieving acute muscle spasms and spasticity due to neurological conditions 6 3 4.
Alcohol Withdrawal: Assist in managing symptoms and preventing complications during alcohol detoxification 2 3 4 5.
Preoperative Sedation: Used to induce relaxation, sedation, or amnesia before surgeries and some medical or dental procedures 1 4 5.
Management of agitation, catatonia, and other acute psychiatric symptoms:
Sometimes used for severe agitation, catatonia, or agitation due to other illnesses 3 5.

Additional Notes

Benzodiazepines may also be used off-label for conditions such as bipolar disorder (for acute mania or agitation), tics, and some rare neurological syndromes 7. They are available only by prescription and should generally be used at the lowest effective dose for the shortest duration possible due to risks of addiction, dependency, tolerance, and withdrawal symptoms 1 2 3 4 5.
Common brand names include Xanax (alprazolam), Valium (diazepam), Ativan (lorazepam), and Klonopin (clonazepam) 4 5.
References