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The following study found that high levels of vitamin D resulted in low levels of medication.
The authors conclude that more medication is needed when vitamin D is high (such as during the summer)
The opposite conclusion can also be made: that less medication is needed during the summer, since vitamin D removes the excess anyway.
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Seasonal Changes in Vitamin D Levels May Affect Medication Absorption

By Sue Russell | Posted March 8 2012

Intriguing results from a Swedish study suggest that doctors may one day adjust the doses of drugs they prescribe to take into account sunlight, the time of year, and seasonal levels of vitamin D in the body.

In 2006, a Canadian study found that grapefruit, orange and apple juices can interfere with the body’s ability to absorb some medications, rendering them less effective. Now, a novel study conducted by scientists at Stockholm’s Karolinska Insitutet suggests that vitamin D levels in the body affect its sensitivity to drugs as well as its ability to break down those drugs and handle toxins.

Researchers at Karolinska have spent decades looking at variables in the effects of medicine, from how different drugs may react when given in combination to how changes in renal function may create a risk for drug toxicity. The idea for examining Karolinska’s existing database to look for season variations in drug absorption struck the study’s four researchers one day while they were discussing vitamin D over a cup of coffee, recalls Erik Eliasson, M.D., Ph.D., associate professor and clinical consultant in Karolinska’s Division of Clinical Pharmacology. “We realized that our clinical laboratory, where we determine the exposure levels to important pharmaceutical drugs—around 100 different drugs and in total around 60,000 patient analyses per year—would provide one of the few tools to actually study whether or not there are seasonal changes in drug exposure levels.”

The study, published in Drug Metabolism and Disposition, tapped into almost 70,000 analyses from patients taking immune system suppressant drugs like tacrolimus, sirolimus and cyclosporine after organ transplantation. All had been followed closely; their blood monitored regularly. The body forms vitamin D when it is exposed to sunlight and the team compared blood samples taken during two distinct periods – the late summer and winter months. “We used a 10 year period,” says Dr. Eliasson, “since we knew this should provide a statistical power to detect even small changes over seasons—i.e. to show this potentially new principle of environmental influence on human detoxification capacity.”

The highest levels of vitamin D due to sunlight exposure were found in the patients when the drug levels in their blood were the lowest. “If the breakdown capacity increases,” said researcher Jonatan Lindh, “then the higher doses of a drug are normally required in order to achieve the same effect.”

“Variability in drug exposure levels,” says Dr. Eliasson, “has already been associated with genetic differences between patients, what other drugs they use, how old they are, if they smoke, and if there are underlying diseases, including inflammation, that affect the process. We have no data yet to support that vitamin D affects drug absorption, rather than drug metabolism, but perhaps specific drug transporters are affected. We don’t know yet.”

A follow-up study is measuring vitamin D in every blood sample taken from a patient during a 12-month period to learn more about the relationship between vitamin D and drug levels. Researchers also will investigate how vitamin D treatment in osteoporosis, as well as in advanced kidney disease, affects how the liver metabolizes drugs.

“We think it adds important information for the understanding of inter-individual variability,” says Dr. Eliasson, “but perhaps it will be most important for patients with vitamin D deficiency, where treatment with vitamin D might affect the dosing of our drugs. We will just need to know more about this, and it is really only early days.”

The team’s research aims to learn more about the right way to individualize drug treatment in order to have more patients reach therapeutic effects and fewer who encounter side effects. Since levels of the transplant rejection drugs in the original study were already closely monitored, doctors compensated for changes in levels with dosage adjustments. So, says Dr. Eliasson, “Perhaps the findings will be more important for other drugs that are not monitored routinely.”

Drugs used by many patients over long periods of time that might warrant a closer look could include, says Dr. Eliasson, medications for high blood pressure or diabetes, antidepressants, antipsychotics and oral contraceptives: “But much work needs to be done in order to understand more about the overall importance.”

One day we may see physicians prescribing higher doses of drugs to compensate for the effect of higher vitamin D levels, but we’re not there yet. “It’s too early to suggest any doctor do that,” says Dr. Eliasson, “but if a patient or doctor notices that the effect of the drug has changed, it might be useful to analyze drug levels.”
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Seasonal Variation in Blood Drug Concentrations and a Potential Relationship to Vitamin D

Jonatan D. Lindh,
Marine L. Andersson,
Erik Eliasson erik.eliasson at ki.se and
Linda Björkhem-Bergman
Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska University Hospital Huddinge, Stockholm, Sweden

The most important enzyme in hepatic drug metabolism is cytochrome P450 3A4. Published in vitro data indicate that vitamin D may up-regulate the expression of the CYP3A4 gene. Individual vitamin D levels are highly dependent on sunlight exposure and show great seasonal variability in northern countries. The aim of the present study was to investigate whether plasma concentrations of CYP3A4 drug substrates exhibit seasonal changes compatible with a stimulatory effect of vitamin D on drug metabolism. Three immunosuppressants (tacrolimus, sirolimus, and cyclosporine) were analyzed, because these CYP3A4 drug substrates are subject to long-term use and repeated concentration determinations. In addition, mycophenolic acid was included in the analysis as a control drug independent of CYP3A4 metabolism. Concentration-to-dose ratios were extracted from the Karolinska Therapeutic Drug Monitoring database and compared between the 3-month periods of lowest and highest vitamin D levels. Sirolimus and tacrolimus levels showed seasonal variability that was highly consistent with changes in vitamin D; for example, significantly lower drug concentrations in July to September than in January to March. As expected, no significant difference was evident for mycophenolic acid, but this result was also the case with cyclosporine, possibly due to cross-reactivity of CYP3A4-mediated metabolites with the immunoassay used for quantification. In conclusion, there is cyclic variation in blood levels of important immunosuppressants throughout the year that correlates with UV light-dependent changes in vitamin D levels. Even though a causal relationship remains to be established, it is suggested that individual differences in vitamin D may contribute to variability in drug metabolism and disposition.
Footnotes

This work was supported by the Stockholm County Council; The Swedish Foundation for Clinical Pharmacology and Pharmacotherapy; the Karolinska Institutet; and the Swedish Research Council [Grant K2006-71X-04496-31-3].

Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.