Sodium Multivitamin Transporter and pharmaconutrition

Y Coleman,

May 1, 2023
Image of our PHarmacoNutrition icon to identify the editorial content category in our MedNut Mail

SMVT (Sodium Multivitamin Transporter) facilitates the uptake of biotin, pantothenic acid, lipoic acid, and iodine from the gut and across the Blood Brain Barrier. It is the only currently known intestinal biotin transporter.

SMVT is present in the small and large intestines, liver, kidney, heart, lungs, brain, cornea, retina, and placenta tissues.

Functions and roles

As a consequence of facilitating the uptake of its substrates ie biotin, pantothenate, lipoic acid, and iodide, SMVT is important in -

  • fatty acid metabolism, and cellular energy production and metabolism,
  • maintaining normal mucosal integrity,
  • being a prognostic marker for gastric cancer,
  • being a drug delivery transport system to increase the availability of prodrugs as conjugates of its biological substrates. For example, biotin-conjugates decrease access to the efflux membrane transporter MDR1 (P-gp).

SMVT deficiencies

SMVT deficiency can be due to -

  • Inherited metabolic disorder – is likely to manifest at a young aged, and typically encompasses feeding problems, failure to thrive, metabolic acidosis, and mild to severe neurological deficits; biotin and pantothenic acid supplementation may confer benefit in some of these disorders;
  • Polymorphisms – likely to manifest at a young aged, and is typically due to mutations in the SLC5A6 gene; biotin and pantothenic acid supplementation may confer benefit in these disorders;
  • Environmental – likely to manifest at any age and is dependent upon the environmental insult; biotin and pantothenic acid supplementation are likely to confer benefit in these disorders; identified causes include -
  • cytokine activation of the NF-kB pathway that typically results in decreased SMVT levels – colitis is an example,
  • chronic alcohol exposure that results in a significant inhibition in both carrier-mediated biotin uptake and SMVT expression,
  • prescribed medicines that inhibit SMVT function (for an unknown duration) and include cefmetazole, captopril, norfloxacin, aspirin, methotrexate, enoxacin, lomefloxacin, levofloxacin, 6-mercaptopurine, indomethacin, salicylic acid.
  • Signs and symptoms that are common to most of SMVT’s substrates include –

    Table identifying signs and symptoms of SMVT deficiency from the editorial component of our MedNut Mail article Sodium multivitamin transporter and pharmaconutrition

    Neonatal screening (aka heel prick test) records are maintained until the person is aged 18 or 21 years, as per State regulations, at which time the records are destroyed. The sample may be used for further testing at the request of the parent or guardian, to provide new medical information for the benefit of the family.

    Clinical Questions

    What actions will you initiate when you see someone whose prescribed medications include SMVT inhibitors, will you –

    • request clarification of biotin, pantothenic acid and iodine status?
    • trial an intervention program and monitor for benefit?
    • recommend nutrient interventions be administered at different times from the prescribed medicines?
    • document the expressed signs and symptoms that support your request, the intervention(s) trialled, and submit as a Case Study at relevant conferences?
    • if the person is young then recommend accessing the person’s neonatal screening and exclude inherited and/or polymorphism contribution?

    Conclusions

    SMVT downregulation and its consequences are not front of mind considerations when reviewing someone with a range of neurological, gastrointestinal and other signs and symptoms, and especially not in adults. Awareness of transporter downregulation is steadily increasing our skill base and consequently improving the outcomes in those in our care.

    Case study

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

    Summary data

    Medical History with Nutritional Aspect

    Image of diagnoses for Mr AGV from the case study in our MedNut Mail article Sodium multivitamin transporter and pharmaconutrition

    Biochemistry with Nutritional Aspect

    Image of blood test results for Mr AGV from the case study in our MedNut Mail article Sodium multivitamin transporter and pharmaconutrition

    Medications That May Adversely Affect Nutritional Status

    Image of prescribed medications for Mr AGV from the case study in our MedNut Mail article Sodium multivitamin transporter and pharmaconutrition

    Transporter-mediated interactions and nutrients

    Image of nutrient, medication, transporter matrix for Mr AGV from the case study in our MedNut Mail article Sodium multivitamin transporter and pharmaconutrition

    Biochemistry 

    Recent relevant biochemistry indicates -

       - low chol 2.5 - atorvastatin ceased 3 months ago;

       - low vit D - commenced vitamin D intervention 3 months ago. Advisable to check vitamin D levels and if still low then review current vitamin D management strategy.

    Glycaemia

    Currently prescribed 5 medications that alter glycaemia, being aspirin, Epilim, metoprolol, paracetamol, perindopril.

    Pharmaconutrition

    The side effects of Mr AGV's prescribed medicines include -

     - 6 medications that include nausea.

    - 5 medications that include anaemia, diarrhoea.

    - 4 medications that include vomiting.

    - 3 medications that include constipation, dry mouth, sweating.

    - 2 medications that include hyponatraemia, tremor, altered appetite.

    Vitamin C (960 mg/day) attenuates aspirin-induced gastric injury.

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

    Epilim decreases biotin and carnitine absorption, decreases availability of folic acid and vitamin D, and may decrease pantothenic acid availability.

    Regular monitoring sodium levels recommended whilst mirtazepine prescribed.

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

    Concurrent ingestion of paracetamol and iron resulted in increased rate of iron absorption and decreased extent of drug absorption; the authors advise drug and iron to be administered at different times from each other.

    Perindopril impairs zinc status.

    Prescribed 2 medications that negatively impact riboflavin status, being metropolol and perindopril. Riboflavin is the rate-limiter in one-carbon metabolism and therefore has an important role in metabolic pathways. Advisable to clarify riboflavin status however if direct testing is unavailable then check pyridoxine and/or niacin status as both these require adequate riboflavin status so they can be activated ie functional.

    Prescribed 2 medications that negatively impact zinc status, being sodium valproate and perindopril. Zinc is important in a range of body functions, including sense of taste, release of the hunger hormone Neuropeptide Y, hearing, bone development, protects thyroid function, protects the mitochondria from oxidative stress and glycation, and altered glomerular function, as well as modifying the inflammatory response pathway and activation of the polyol pathway (a part of intracellular signalling and metabolism). Advisable to monitor zinc status on a regular basis ie at least annually and if low then short term (90-120 days) intervention recommended.

    Bowel management 

       Regular aperient prescribed.

       Oral PRN aperient prescribed; administered 1 x Jun, 1 x Apr.

       Nurse Initiated anal intervention administered 1 x Apr.

    Staff comments

    Staff advise Mr AGV eats well.

    Observations

    Mr AGV is a slender, pale Turkish man who had just finished eating his midday meal when I went to speak to him - he had eaten everything.

    Mr AGV has remained weight stable for the last year.

    Pharmaconutrition assessment

    Staff expressed concern about the delayed wound-healing on Mr AGV’s (L) toe. Nutritional factors that contribute to wound healing include -

       - adequate vitamin D status - evidence indicates low vitamin D status is associated with delayed wound healing. Currently prescribed both a vitamin D intervention and a medicine that decreases vitamin D availability, being Epilim. Advisable to clarify current vitamin D status and if still very low then recommend reviewing current intervention with a view to increasing current dose.

       - adequate vitamin and mineral intake – current combination of prescribed medications negatively impact iron, zinc, sodium, vitamin C, B12, folic acid, thiamine, biotin, carnitine, and likely pantothenic acid therefore advisable to consider either monitoring all these nutrients on a regular basis (at least annually) or commence a prophylactic intervention that is administered at a different time from the other prescribed medications (some authors are now advocating this strategy as their preferred option).

    Falls

    Mr AGV’s diagnoses include falls. Nutritional factors that may be useful to consider in falls management include -

       - loss of weight – most of the prescribed medications include side effects that negatively impact food intake either directly or indirectly;

       - vitamin D – associated with muscle weakness and consequently falls. Currently prescribed Epilim therefore advisable to clarify vitamin D status;

       - B12 - is important in the righting reflex when a person stumbles. Prescribed Epilim therefore advisable to monitor status;

       - iron – currently prescribed aspirin therefore advisable to monitor status;

       - zinc – low levels can decrease food intake through altered sense of taste and poor appetite, and consequently reduced muscle mass. Currently prescribed Epilim and perindopril therefore advisable to monitor status;

    - low carnitine - carnitine is both absorbed and produced de novo, and is important in a range of muscle functions. Epilim decreases carnitine absorption and magnesium is important in de novo carnitine production. Advisable to clarify carnitine status.

    What else would you include?

    Please read this as it is important …

    The information in this article is provided to support Health Professionals. It is not an exhaustive protocol and Health Professionals are advised that adequate professional supervision is accessed to ensure that Duty of Care obligations with respect to safe administration of medicines is met for each consumer.

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