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Journal of Drug Delivery and Therapeutics
Open Access to Pharmaceutical and Medical Research
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Open Access Full Text Article Review Article
Drug-Induced Nutrient Depletion in Palliative Care Patients: Clinical Implications and Management
Lahari Samudrala 1*, Y. Sneha 2*, Chitti Sathwika 2, Meghavath Tharun 2, Uma Maheshwararao 3
1 Assistant Professor, Department of Pharm D, CMR College of Pharmacy, Hyderabad, India
2 Student, Department of Pharm D, CMR College of Pharmacy, Hyderabad, India
3 Principal, M. Pharm, Ph. D, CMR College of Pharmacy, Hyderabad, India
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Article Info: _____________________________________________Article History: Received 10 May 2026 Reviewed 06 July 2026 Accepted 28 July 2026 Published 15 August 2026 _____________________________________________ Cite this article as: Samudrala L, Sneha Y, Sathwika C, Tharun M, Maheshwararao U, Drug-Induced Nutrient Depletion in Palliative Care Patients: Clinical Implications and Management, Journal of Drug Delivery and Therapeutics. 2026; 16(8):189-195 DOI: https://doi.org/10.22270/jddt.v16i8.7886 _____________________________________________ For Correspondence: Samudrala Lahari, Assistant Professor, Department of PharmD, CMR College of Pharmacy, Kandlakoya, Medchal, Hyderabad, India-501401. |
Abstract _______________________________________________________________________________________________________________ Drug-Induced Nutrient Deficiencies are an important but often underappreciated adverse effect of long-term pharmacotherapies. A wide variety of medications are known to affect the absorption, metabolism, distribution, or excretion of key vitamins and minerals, including proton pump inhibitors, metformin, diuretics, anticonvulsants, antibiotics, corticosteroids, and oral contraceptives. Disturbances in vitamin B12, folate, vitamin D, calcium, magnesium, potassium, and fat-soluble vitamins are among nutrients that commonly result in clinically significant deficiencies. Although these nutrient deficiencies often develop slowly, they have the potential to cause significant disease. Patients at highest risk include the elderly, individuals with chronic diseases, those receiving multiple medications, and patients on prolonged therapy with agents known to induce nutrient losses. It is important to ensure early identification by targeted screening, education of the patient, and routine monitoring to prevent complications. Nutrient assessment as part of therapeutic planning enables clinicians to predict the likelihood of deficiencies even before symptoms become evident. This review synthesizes current evidence of medications most commonly associated with nutrient depletion, outlines key mechanistic pathways, and discusses clinical implications related to patient care. It also underlines strategies for monitoring and managing nutrient deficiencies, putting particular emphasis on the healthcare professional's role, especially clinical pharmacists in optimizing therapy and avoiding adverse outcomes. Greater awareness regarding drug-induced nutrient deficiencies will lead to improved medication safety and management that is holistic in its approach to patients. Identifying at-risk individuals, instituting preventative measures, and incorporating nutritional considerations into pharmacotherapy may yield significant improvements in overall treatment outcomes. These deficiencies are particularly significant in palliative care settings, where polypharmacy and chronic illness increase vulnerability, making early recognition essential for improving quality of life. Keywords: Drug-Induced Nutrient Deficiencies, absorption, metabolism, distribution, vitamins and minerals |
The consumption of drugs has increased significantly worldwide, due to increases in chronic diseases, life expectancy, and access to medical care. Because most patients are treated for years and often with more than one type of medication, the potential for adverse effects of drug–nutrient interactions have become a significant yet often overlooked component of clinical practice. Although the therapeutic benefits of medications are widely recognized, there is little emphasis on their ability to disrupt the body's nutritional status.
Drug-Induced Nutrient Deficiencies arise when medications interfere with the absorption, metabolism, transport, storage, or excretion of important vitamins and minerals. , These interferences may occur gradually and remain clinically silent for a long time until there are significant physiological changes. The following medications have been consistently implicated in the depletion of important nutrients: proton pump inhibitors, metformin, diuretics, anticonvulsants, corticosteroids, and antibiotics. The critical nutrients so far implicated include vitamin B12, vitamin D, folate, calcium, magnesium, potassium, and the fat-soluble vitamins. When these deficiencies are not identified, they contribute to a wide variety of preventable complications that include anemia, neuropathy, bone demineralization, electrolyte disturbances, immune dysfunction, and metabolic disorders.
Although the clinical relevance is great, drug-induced nutrient deficiencies remain largely unidentified in the routine health care environment. The populations more vulnerable to this kind of deficiency include the elderly, chronically ill, those on restrictive diets, and those receiving polypharmacy; However, no standard practice of screening for nutrient depletions exists in either setting.
The purpose of this review is to provide an overview of medications commonly associated with nutrient deficiencies, explain the biological mechanisms of these interactions, outline clinical consequences, and provide evidence-based strategies for monitoring and prevention. By raising awareness of such interactions, healthcare professionals may better anticipate risk, individualize therapy, and enhance patient outcomes.
Drug-Induced Nutrient Deficiencies arise from numerous pharmacological and physiological processes. These different mechanisms may act alone or in concert, and the degree to which each plays a role often depends on drug dose, duration of therapy, and individual patient factors.
Broad-spectrum antibiotics significantly affect the intestinal flora that are responsible for synthesizing some vitamins.
Some drugs interfere with the proteins or cofactors required for nutrient transport or biological activation.
Overall, medications can disrupt nutritional status through multiple pathways, often gradually and without immediate symptoms.
Drug classes associated with Nutrient Deficiencies
A wide range of commonly prescribed medications have been linked to specific nutrient deficiencies through their effects on absorption, metabolism, excretion, or biological utilization.
|
Drug Class |
Drugs |
Nutrients affected |
Mechanism |
Clinical implications |
|
Proton pump inhibitors |
Omeprazole, Pantoprazole |
Vitamin B12, Magnesium, Calcium, Iron7, |
Reduces gastric acid, impairs absorption |
Anemia, fractures, hypomagnesemia |
|
Anti- convulsants |
Phenytoin, Carbamazepine, Phenobarbital, Valproate |
Vitamin D, Folate, Vitamin B6 , |
Hepatic enzyme induction, increases metabolism |
Osteoporosis, anemia, neuropathy |
|
Loop diuretics |
Furosemide |
Potassium, Magnesium, Calcium, Sodium, Thiamine |
Increased renal excretion |
Arrhythmia, weakness, electrolyte disturbances |
|
Thiazide diuretics |
Hydrochlorothiazide |
Magnesium, Potassium |
Renal electrolyte loss |
Fatigue, muscle cramps |
|
Broad- spectrum Antibiotics |
Cephalosporins, Fluoroquinolones |
Vitamin K, B-complex vitamins |
Destruction of gut microbiota |
Bleeding tendency, fatigue |
|
Oral contraceptives |
Combined OCPs |
Folate, B6, B12, Magnesium, Zinc |
Altered metabolism, hormone- mediated changes |
Increased homocysteine, mood changes |
|
Anti- TB drugs |
Isoniazid |
Vitamin B6 , |
Formation of inactive complexes |
Peripheral neuropathy |
|
Corticosteroids |
Prednisolone, Dexamethasone |
Calcium, Vitamin D, Potassium |
Reduced absorption, increased excretion |
Osteoporosis, muscle weakness |
|
Antacids |
Aluminum/ Magnesium antacids |
Iron, Phosphate, B vitamins , |
Reduced acidity and binding effects |
Anemia, fatigue |
|
Bile acid sequestrants |
Cholestyramine, Colestipol |
Vitamins A, D, E, K, Folate |
Binding of fat- soluble vitamins |
Coagulopathy, bone changes |
|
Chemotherapeutics |
Methotrexate, 5- fluorouracil |
Folate, Thiamine |
Inhibition of folate pathways |
Anemia, mucositis |
|
Metformin |
Metformin ER/IR |
Vitamin B12 |
Impaired calcium dependent ileal absorption |
Neuropathy, anemia |
Recognition of these relationships allows the clinician to predict deficiencies, appropriately screen patients, and intervene early to avoid unfavorable outcomes.
Physiological, metabolic, and pharmacological factors can make specific vulnerable populations more prone to drug-induced nutrient deficiencies.
In palliative care settings, patients are often elderly with multiple comorbidities and are exposed to prolonged polypharmacy. These factors significantly increase the risk of drug-induced nutrient deficiencies, which may further worsen fatigue, cognitive decline, and overall quality of life.
Older adults have reduced gastric acidity, lower dietary intake, polypharmacy, and age-related malabsorption-all of which contribute to increased risk of deficiency. Medications that are commonly used in this population, including PPIs, metformin, diuretics, and antiepileptics, further compromise nutrient status. Due to cognitive impairment and/or frailty, symptoms may be masked, with deficiencies underdiagnosed.
Such as diabetes, chronic kidney disease, inflammatory bowel disease, cardiovascular disease, and epilepsy, often require long-term drug therapy. Their underlying disease may already cause impairment to nutrient absorption, metabolism or excretion, making them highly susceptible to drug-nutrient interactions. ,
Pregnancy increases the need for micronutrients such as folate, iron, vitamin B12, and vitamin D. Some drugs including anticonvulsants, antiretrovirals, and certain antibiotics, increase the risk of deficiency with potential adverse maternal and fetal consequences.
Patients with diseases that impede nutrient absorption, such as celiac disease, bariatric surgery, short bowel syndrome, or chronic diarrhea, are at increased risk of deficiencies if they are exposed to drugs that further impair nutrient absorption. ,
Those on long-term therapies, for example, PPIs >2 years, metformin >5 years, corticosteroids, cholestyramine, and antiepileptics, risk cumulative nutrient depletion over time. ,
People with diets low in intrinsic B12, iron or fat-soluble vitamins will develop deficiencies more quickly when medications interfere with the absorption or metabolism of the few nutrients they get from their diet. ,
Chronic use of alcohol disrupts hepatic metabolism, decreases intake, and impairs vitamin absorption. The use of concurrent medications such as isoniazid, diuretics, or antiepileptics may exacerbate nutrient depletion.
Drug-induced nutrient deficiencies can cause various physiological, neurological, haematological, and metabolic complications. The severity depends on the specific nutrient affected, duration of medication use, underlying comorbidities, and patient age.51
Medications that interfere with the absorption or metabolism of vitamin B12 and folate may result in macrocytic anaemia, fatigue, pallor, glossitis, and decreased exercise tolerance. The drugs most frequently associated with deficiencies of these nutrients are methotrexate, antiepileptics, PPIs, and metformin. Iron deficiency caused by the administration of acid-suppressing therapy also leads to microcytic anaemia and a defective immune response. ,
Vitamin B12, B6, and folate deficiencies can present with peripheral neuropathy, paresthesia, cognitive decline, depression, irritability, and in more severe cases, subacute combined degeneration of the spinal cord. Contributory factors commonly include prolonged metformin, isoniazid, and oral contraceptives. ,
Drugs that interfere with the resorption of vitamin D, calcium, and magnesium may result in osteomalacia, muscle cramps, tetany, bone demineralization, and increased fracture risk. The most common cause of drug-induced osteoporosis is corticosteroid-induced calcium depletion.
Nutrient depletion including potassium, magnesium, or thiamine may precipitate arrhythmias, hypertension, heart failure exacerbation, or impaired myocardial contractility. Diuretic-induced electrolyte loss is particularly associated with dangerous ventricular arrhythmias.
Vitamin K deficiency caused by suppression of gut flora by antibiotics may present as prolonged bleeding, easy bruising, and elevated INR.24 Deficiencies of the fat-soluble vitamins due to bile acid sequestrants or lipase inhibitors may present with steatorrhea, night blindness, or wound healing impairment.
Zinc, vitamin A, and vitamin D deficiencies, caused by chronic drug intake, will precipitate impaired immune responses, enhanced risk to infection, and impaired glucose and lipid metabolism. This impact is increased in subjects with chronic diseases.
Folate and vitamin B6 depletion associated with antiepileptics or oral contraceptives elevate the risk of neural tube defects in pregnancy. Vitamin A and D deficiencies might further compromise fetal development and maternal skeletal health.
A structured approach to risk assessment, targeted laboratory evaluations, and individualized supplementation will go a long way toward improving patient outcomes.
Before the initiation of long-term therapies known to affect nutrient status, it is appropriate for clinicians to check baseline levels of important vitamins. Depending on the medication, baseline tests may involve vitamin B12, folate, vitamin D, calcium, magnesium, potassium, and iron studies.20
This targeted approach reduces unnecessary testing while ensuring early detection of emerging deficiencies.
Patients should receive guidance on nutrient-rich dietary patterns to counteract medication-induced losses. Examples include increasing leafy greens for folate, lean meats for B12, and dairy or fortified foods for calcium and vitamin D, while magnesium and potassium should be derived from whole foods.2
Supplementation in appropriate cases, when deficiencies are identified or anticipated, prevents clinical deterioration:
Regular medication reconciliation helps identify and reduce unnecessary polypharmacy.9 Deprescribing or switching to a lower-risk alternative, for instance, step-down therapy from PPIs where appropriate can substantially reduce the deficiency risk.
Patient education on early deficiency symptoms such as numbness, generalized fatigue, muscle cramps, or palpitations encourages better self-monitoring and promotes timely medical evaluation.
Integration of pharmacists, dietitians, and physicians enhances screening efficiency and ensures comprehensive care. Pharmacists can flag high-risk medications, while dietitians tailor nutrient intake plans, creating a coordinated prevention strategy.
Drug-Induced Nutrient Deficiencies are still an under-recognized but clinically significant consequence of long-term pharmacotherapy. If left unattended, such nutrient losses may manifest themselves in the form of anemia, neuropathy, bone demineralization, immune dysfunction, metabolic abnormalities, and other preventable complications.
These deficiencies, though common, often go unnoticed in routine clinical practice due to a lack of appropriate screening, especially in the more vulnerable groups of patients. Early identification through appropriate screening with targeted supplementation and ongoing monitoring can greatly reduce the risk of adverse outcomes. Clinical pharmacists, physicians, and nutrition specialists play a critical role in identifying at-risk patients and in integrating nutrient monitoring into therapeutic decision-making.
Ultimately, a better understanding of drug–nutrient interactions is required to ensure safe and optimized pharmacotherapy. The integration of nutrient assessment into routine care pathways, along with education for health professionals and the promotion of awareness for patients, can together serve to reduce the burden of drug-induced deficiencies. All these practices, when strengthened, will lead to improved health outcomes with fewer medication-related complications and offer more comprehensive patient care.
References