Aspirin-vitamin C interactions

The aspirin-vitamin C interaction was discovered in the early 1970’s. The evidence is predominantly based on short term, high-dose interventions and there is minimal evidence of low-dose, long term interventions. Currently there are no commonly prescribed clinical interventions for this interaction.

Vitamin C transporters include -

• SVCT1 (Sodium Vitamin C Transporter 1) – primarily involved in maintaining the body’s vitamin C status; interaction with aspirin seems unlikely;
• SVCT2 –primarily involved in cellular uptake of ascorbic acid; no interaction with aspirin;
• SVCT3 – function unknown therefore likely interaction with aspirin unknown;
• GLUT1 (Glucose Transporter 1) – transports ascorbic acid into the mitochondria to confer protection from oxidative damage. GLUT1 transports dehydoascorbic acid (DHA) into cells where it is reduced to ascorbic acid; aspirin inhibits and/or regulates GLUT1;
• GLUT2/3/4/8 – can transport DHA; likelihood of interaction with aspirin unknown.

As DHA and glucose have similar three-dimensional structures glucose concentration in plasma also affects DHA transport.

Speculatively, aspirin negatively impacts vitamin C status by increasing cellular antioxidant capacity due to aspirin-induced mucosal damage.

However, utilization of the technological combination of voltammetry, infrared, three-dimensional fluorescence and circular dichroism in 2020 (https://doi.org/10.1016/j.saa.2020.118356), has ascertained that aspirin influences the binding process of Vitamin C to albumin. Further, the authors conclude timing of vitamin C administration in relation to aspirin administration is important. Vitamin C does not alter aspirin absorption, therefore advisable to administer vitamin C prior to administering aspirin. However, if aspirin is administered first then there is a consequent reduction in vitamin C absorption.

The recommendation during long term aspirin therapy is for the ascorbic acid dose to be increased to 100 – 200 mg.

Aspirin apparently inhibits vitamin C absorption by 2 mechanisms –

   1. inhibition of GLUT1 cellular uptake of DHA;

   2. inhibition of vitamin C binding to albumin.

Being a drug-protein interaction, this aspirin-vitamin c interaction is indicative of a new mechanism of action in drug-nutrition interactions.

Clinical Considerations

When would be the best time to administer a vitamin C intervention when aspirin is prescribed? Since the recommended timing for aspirin administration is with food, then vitamin C administration options are either one hour prior to the same meal, or administered at another defined time.

Clinical Questions

What actions will you initiate as you a review a person whose prescribed medications include aspirin, will you –

• clarify duration of prescription and consider recommending a vitamin C intervention, and at what dose?
• recommend an administration time of the vitamin C intervention?
• recommend the Medications Advisory Committee develop guidelines for administration of vitamin C when aspirin is prescribed?

Conclusions

Case study

The comments refer to the drug-nutrient, drug-food, and PharmacoNutrition effects only.

Data summary

Medical History with Nutritional Aspect

Biochemistry with Nutritional Aspect

Medications That May Adversely Affect Nutritional Status

Transporter-mediated interactions and nutrients

Biochemistry 

Recent relevant available biochemistry indicates –

   - marginal Hb + elevated MCV – currently prescribed paracetamol therefore advisable to monitor status and ensure marginal status is resolving;

   - elevated normal TSH - evidence indicates increased risk of altered thyroid function in the elderly once TSH > 2.5;

   - high-normal B12 status – and currently prescribed a B12 intervention. Advisable to review either the necessity for its continued administration or to reduce the frequency of the intervention;

   - elevated TSH – which is diagnostic for altered thyroid function. As metoprolol which masks altered thyroid function currently prescribed advisable to clarify current status of thyroid function;

   - elevated CRP+ESR - inflammatory response markers that are associated with increased resting metabolic rate and consequent increase in energy (food) requirements. Vitamin D status influences inflammatory response markers, and prescribed a vitamin D intervention therefore advisable to clarify vitamin D status;

   - marginal vit D - currently prescribed an intervention. Advisable to check vitamin D levels and if still low then review current vitamin D management strategy.

Glycaemia 

Currently prescribed 3 medications that include hyperglycaemia and/or hypoglycaemia as side effects.

Pharmaconutrition

Currently prescribed-

 - 6 medications that include nausea aside effect;

 - 5 medications that include diarrhoea a side effect;

 - 4 medications that include hypokalaemia, vomiting and constipation as side effects;

 - 3 medications that include altered taste, dry mouth and sweating as side effects.

Coffee inhibits vitamin D uptake by inhibiting the osteoblasts (bone builders) vitamin D receptors, consequently decreasing calcium and zinc absorption.

Chronic use of coloxyl + senna may promote excessive loss of water and electrolytes, especially potassium, and their regular monitoring recommended.

Dietary levels of caffeine intake in conjunction with paracetamol inhibit antinocieception.

Concurrent ingestion of paracetamol component and iron resulted in increased rate of iron absorption and decreased extent of drug absorption. Consequently, the authors advise different administration times from each other for the drug and iron.

The identified membrane transporters inhibit the absorption and/or organ and cellular uptake of thiamine, choline, carnitine, pyridoxine and NMN (B3). Consequently, blood test results are likely to indicate normal or elevated status because nutrients are prevented from entering relevant cells. Advisable for blood tests to be conducted several hours after administration of relevant prescribed medicines.

Bowel management

   Regular aperient prescribed.

   Oral PRN aperient prescribed; administered 1 x this month.

   No Nurse Initiated interventions administered.

Staff comments

Staff advise Mrs ACP is recovering from a recent significant infection. Further, staff commented that during the duration of the infection Mrs ACP ate sparingly, and now her appetite is improving.

Observations

Mrs ACP is a small, pale, frail lady who was sitting up in bed when I saw her. Mrs ACP answered all my questions appropriately and briefly - she seems to be quite a character.

Weight remained stable about 50 kg from admission until 6 months ago then started to go down. Staff attribute Mrs ACP’s weight loss to her recent unwellness.

Pharmaconutrition comments

Although Mrs ACP is pale, the latest SIS results indicate her IDA is resolving.

Mrs ACP’s diagnoses include B12, zinc and iron deficiencies however an intervention has been initiated for B12 deficiency only. If iron and zinc interventions are initiated then administer at different times from each other as they share the same absorption mechanism.

Wound healing

Mrs ACP’s diagnoses include a pressure area - nutritional interventions that support to wound healing include -

   - ensure adequate status of B12, zinc and iron. Currently commenced a B12 intervention, micardis impairs zinc availability and paracetamol masks iron status;

   - adequate vitamin D status. Evidence indicates low vitamin D status is associated with delayed wound healing albeit currently prescribed a vitamin D intervention.

Chronic pain

Mrs ACP’s diagnoses include chronic pain - nutritional factors that may be useful to consider in pain management include -

   - vitamin D - current intervention may not be adequate to attain adequate range. Evidence indicates increasingly brittle pain control with decreasing vitamin D levels;

   - evidence indicates neuropathic pain relief of by thiamine, pyridoxine and cobalamin separately, synergistic benefit in combination;

   - low B12 exacerbates elevated TNF- α which is an inflammatory response marker and its elevation can include a pain response. Currently prescribed a B12 intervention therefore advisable to clarify B12 status.

What else would you include?

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