Vitamin B1 (Thiamine)
Nutrient Name: Vitamin B1, thiamine.
Synonyms: Thiamin, thiamine.
Related Substances: Aneurine hydrochloride, thiamine hydrochloride, thiaminium chloride hydrochloride; benfotiamine; tetrahydrofurfuryl disulfide (TTFD).
| Drug/Class Interaction Type | Mechanism and Significance | Management | Antacids
| Antacids interfere with the absorption of thiamine and other nutrients. | Separate intake of thiamine sources and antacids by at least 2 hours. | Antibiotics
| Repeated or protracted administration of broad-spectrum antibiotics can destroy beneficial intestinal flora and disrupt healthy gut ecology, including production of B vitamins. Mechanism is widely recognized, but clinical significance and long-term implications are just beginning to be acknowledged and understood. | Administration of diverse probiotic is judicious after significant antibiotic therapy. Multivitamin supplementation may be indicated if deficient. | Fluorouracil (5-FU)
Antimetabolite chemotherapeutic agents
 /   /
| Fluorouracil interferes with conversion of thiamine to thiamine pyrophosphate as a means of inhibiting DNA and RNA synthesis and tumor cell proliferation. Mechanism and probability of this interaction are axiomatic, and its clinical significance is fundamental to use as chemotherapeutic strategy. | Thiamine restriction and depletion essential, but intermittent dietary enhancement or supplementation may be appropriate. Supervision and monitoring critical. | Furosemide
Loop diuretics
/  /
| Furosemide and other loop diuretics can increase urinary thiamine excretion and induce thiamine depletion, which can contribute to cardiac insufficiency and aggravate congestive heart failure. With mechanism and prevalence of this adverse effect reaching consensus, so has appreciation of its profound clinical significance and long-term implications. Changes in medical practice are emerging. | Coadminister with diuresis longer than 1 month. Monitor for deficiency symptoms. | Nortriptyline
Tricyclic antidepressants (TCAs)
/
| Response improved with coadministration of antidepressants, including nortriptyline and TCAs, and B vitamins, particularly thiamine. Mechanism undetermined: prevention of nutrient depletion or promotion of active synergistic effect, or both. Evidence preliminary but with strong positive trend. Clinical significance and individual patient factors still undefined. | B-complex coadministration judicious and considered safe, especially with probable deficiency. | Oral contraceptives (OCs)
/
| Variable decreases in levels of thiamine and other nutrients associated with OC use. Clinical significance controversial; evidence mixed. | B-complex coadministration judicious and considered safe, especially with probable deficiency. | Phenytoin
Anticonvulsant medications
/
| Phenytoin interferes with thiamine function, particularly in brain, CNS, and CSF. Antiepileptic drugs may deplete thiamine (and folate), and supplementation may enhance therapeutic effect. | Coadminister with anticonvulsant therapy longer than 1 month. Monitor for deficiency symptoms. | Scopolamine
/
| Scopolamine may interfere with CNS functions of thiamine, particularly involving acetylcholine. Preliminary evidence of reduced adverse effects with thiamine coadministration. Clinical significance probable. | Coadminister; may require high doses under supervision. | Stavudine
Reverse-transcriptase inhibitor (nucleoside) antiretroviral agents
/
| Thiamine used to counter severe lactic acidosis associated with stavudine, alone or with HAART protocols, particularly in patients with genetic susceptibility or preexisting vitamin deficiency. Evidence from anecdotal reports, but pattern consistent. | Preventive B-complex coadministration prudent. Intravenous thiamine administration indicated in critical cases. Close supervision, monitoring. | Tetracycline
Tetracycline antibiotics
| Thiamine and other B-complex vitamins may interfere with tetracycline pharmacokinetics. Concomitant intake may significantly impair bioavailability. Evidence minimal but not controversial. | Avoid thiamine and B vitamins. If necessary, separate intake by 4 hours. | CNS , Central nervous system; CSF , cerebrospinal fluid; HAART , highly active antiretroviral therapy. |
Chemistry and Forms
In 1926, thiamine was the first B vitamin isolated, as a crystalline, water-soluble, yellowish white powder with a salty, slightly nutty taste. By 1936 it had been synthesized and its chemical structure determined. This substance is heat and oxygen stable in its dry form, heat and alkali reactive in solution, and stabilized by acid.
Physiology and Function
Thiamine uptake by active transport is highest in the jejunum and ileum, with both passive diffusion and active, carrier-mediated transport. Throughout the small intestine, and generally by cells in various organs, absorption is mediated by a saturable, high-affinity transport system, and once absorbed, thiamine is primarily transported in the serum bound to albumin. In humans, thiamine can be synthesized in the large intestine as thiamine pyrophosphate (TPP). Too large a molecule to be absorbed across the intestinal mucosa, TPP requires the use of an enzyme to cleave the smaller thiamine molecule out of the compound. Skeletal muscle, heart, liver, kidneys, and the brain are sites of particularly high concentrations, although only small amounts of thiamine (30-70 mg) are typically stored in the body.
Thiamine is required for all tissues as a coenzyme in the metabolism of carbohydrates and branched-chain amino acids, particularly in the tricarboxylic acid (TCA) cycle and pentose phosphate shunt. Thiamine needs to be phosphorylated to become metabolically active, and thiamine diphosphate is its active form. Thiamine diphosphate is a cofactor for several important enzymes involved in the biosynthesis of neurotransmitters and various cell constituents, for the production of reducing equivalents used in oxidative stress responses, and for the biosyntheses of pentoses (e.g., ribose, deoxyribose) used as nucleic acid precursors. When it combines with two molecules of phosphoric acid, thiamine will form TPP. Functioning as a co-carboxylase, TPP is required for the oxidative decarboxylation of pyruvate to form active acetate and acetyl coenzyme A. It is also required for the oxidative decarboxylation of other alpha keto acids such as α-ketoglutaric acid and the 2-keto-carboxylates derived from the amino acids methionine, threonine, leucine, isoleucine, and valine. TPP is also involved as a coenzyme for the transketolase reaction, which functions for the pentose monophosphate shunt pathway. With a specific role in neurophysiology separate from its coenzyme function, TPP works at the nerve cell membrane to allow displacement so that sodium ions can freely cross the membrane. Although thiamine is needed for the metabolism of carbohydrates, fat, and protein, it is especially central to carbohydrate metabolism in the brain. In addition to providing TPP, thiamine becomes part of thiamine triphosphate, which appears to have an important function in brain cell viability. Thiamine is also required in acetylcholine and fatty acid synthesis.
Research is ongoing into the genetic and biochemical factors contributing to interindividual differences in susceptibility to development of disorders related to thiamine deficiency, as well as the differential vulnerabilities of various tissues and cell types.
Known or Potential Therapeutic Uses
Thiamine deficiency manifests primarily as disorders of the nervous, cardiovascular, muscular, and gastrointestinal systems. Deficiency symptoms include: fatigue, weight loss, depression, irritability, memory loss, mental confusion, heart palpitations, tachycardia, anorexia, indigestion, edema, neuritis, neuropathies, paresthesia, hyporeflexia (especially of legs), defective muscular coordination, muscular weakness, and sore muscles (especially calves).
Historical/Ethnomedicine Precedent
Beriberi, the classic thiamine deficiency disease.
Possible Uses
Alcoholism, Alzheimer's disease, anxiety, atherosclerosis, canker sores, chronic dieting, congestive heart failure (CHF), Crohn's disease, depression, diabetes mellitus, dysmenorrhea, fibromyalgia, glaucoma, hepatitis, human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS) support, insomnia, Kearns-Sayre syndrome, Leigh's disease, minor injuries, mosquito repellant, multiple sclerosis, neuropathy (especially benfotiamine), roundworms, sciatica, sensory neuropathy (diabetic), trigeminal neuralgia, Wernicke-Korsakoff syndrome; diets consisting primarily of highly processed, refined foods; treatment of thiamine deficiency–related disorders, including cardiovascular (wet) beriberi, nervous (dry) beriberi, Wernicke's encephalopathy syndrome, and peripheral neuritis associated with pellagra (vitamin B3deficiency); alcoholic patients with altered sensorium; various genetic metabolic disorders, such as thiamine-responsive megaloblastic anemia.
Dietary Sources
Pork, liver, chicken, fish, beef, wheat germ, dried yeast, cereal products, lentils, potatoes, brewer's yeast, rice polishings, most whole-grain cereals (especially wheat, oats, and rice), all seeds and nuts, beans (especially soybeans), milk and milk products, vegetables such as beets, green leafy vegetables.
Most plant and animal foods contain some thiamine, but the richest dietary sources are brewer's yeast and organ meats.
Thiamine deficiency is one of the most common nutritional deficiency patterns in modernized societies. Almost half the U.S. population consumes less than half the recommended daily allowance (RDA) of thiamine, according to the U.S. Department of Agriculture. Although whole grains may be rich in thiamine, processing of grains significantly reduces their thiamine content. Likewise, because thiamine is water soluble and heat sensitive, cooking largely results in the loss or destruction of this vitamin, especially when chlorinated water is used.
Clinical signs of thiamine deficiency primarily involve the nervous, cardiovascular, muscular, and gastrointestinal systems. Adults have the following symptoms:
- Mental confusion, anorexia, muscle weakness, calf muscle tenderness, ataxia, indigestion, constipation, tachycardia with palpitations.
- Wet beriberi: edema starting in the feet and progressing upward into the legs, trunk, and face, eventually resulting in death from cardiac enlargement and CHF.
- Dry beriberi: worsened polyneuritis in early stages (particularly peripheral neuritis), difficulty walking, and muscle wasting, especially atrophy of the legs.
The distinction between wet (cardiovascular) and dry (neuritic) manifestations of beriberi usually relates to the duration and severity of the deficiency, the degree of physical exertion, and the caloric intake. The wet or edematous condition results from severe physical exertion and high carbohydrate intake. The dry or polyneuritic form stems from relative inactivity with caloric restrictions during the chronic deficiency.
Wernicke-Korsakoff syndrome is the classical manifestation of central nervous system (CNS) deficiency of thiamine caused by alcoholism. Patients present with impaired memory and cognitive function, irritability, and nystagmus caused by weakness in the sixth cranial nerve; coma is a common end state. Vitamin B1is necessary for the metabolism of alcohol, but alcohol interferes with its absorption, making malnourished alcoholics often severely thiamine deficient. Alcoholics given intravenous (IV) glucose without thiamine are at high risk of developing Wernicke-Korsakoff syndrome and sustain permanent neurological damage, because the glucose, which also requires thiamine for its metabolism, rapidly depletes remaining tissue levels of brain thiamine. For this reason, an IV “cocktail” of glucose, thiamine, and a narcotic antagonist is typically administered in emergency rooms to unconscious patients who present with unconsciousness of unknown etiology.
Infant symptoms appear suddenly and severely, involving cardiac failure and cyanosis.
The etiology of thiamine deficiency can be traced to an exclusive diet of milled, nonenriched rice or wheat, raw fish consumption (microbial thiaminases), large amounts of tea, alcoholism (impaired absorption and storage, poor nutrition, increased thiamine utilization), use of loop diuretics, and several inborn errors of metabolism.
Special Populations
Individuals with alcoholism, anorexia, CHF, Crohn's disease, folate deficiency, malabsorption syndrome, and multiple sclerosis are at increased risk of developing thiamine deficiency, as are those undergoing long-term diuretic therapy, hemodialysis, or peritoneal dialysis.
Alcoholic individuals frequently develop a deficiency of thiamine because the vitamin is a necessary cofactor in the metabolism of alcohol. Because many alcoholics tend to eat less and drink more, and usually their alcohol-based drinks are low in thiamine, they frequently develop a thiamine deficiency. In hospitals it is routine for alcoholics to receive intramuscular (IM) injections of thiamine on admission.
Elderly persons demonstrate a general decline in thiamine levels that is apparently related more to age than to coexisting illness or health status. This increased susceptibility enhances the risk for adverse effects of drug-induced depletion, especially in regard to cardiovascular health and cognitive stability.
Nutrient Preparations Available
Thiamine, water soluble. Thiamine hydrochloride is generally considered the preferred supplemental form of thiamine. Thiamine mononitrate is also available. Thiamine supplementation is usually provided in vitamin B–complex formulations, in most multivitamin preparations, and in vitamin-enriched foods, such as breakfast cereals.
Benfotiamine is a lipid-soluble form of thiamine developed and patented in Japan, now widely used in neuropathy therapies.
Dosage Forms Available
Capsule, liquid, tablet, effervescent tablet; liposomal spray. Parenteral form may be administered by IM or slow IV injection.
Source Materials for Nutrient Preparations
Synthesized.
Dosage Range
The RDA for thiamine varies slightly with gender and life stage.
- Men (>19 years): 1.2 mg/day
- Women (>19 years): 1.1 mg/day
- Pregnancy and breastfeeding (any age): 1.4 mg/day
Adults
- Supplemental/Maintenance: Dependent on dietary intake, usually 1 to 2 mg/day. A paper on the “ideal” daily thiamine intake reported that the healthiest people consumed more than 9 mg/day.
- Pharmacological/Therapeutic: 1.5 to 200 mg/day. In research studies, therapeutic dosage for most conditions ranges from 10 to 100 mg/day, in divided doses. In clinical practice, 200 to 600 mg/day may be given, and some clinicians have used oral dosages as high as 8 g/day, in divided doses, for a variety of metabolic disorders.
- Thiamine deficiency (beriberi): 5 to 30 mg per dose, intramuscularly (IM) or intravenously (IV), three times daily (if critically ill); then orally 5 to 30 mg/day in single or divided doses, three times daily for 1 month.
- Wernicke's encephalopathy: 100 mg IV initially, then 50 to 100 mg/day IM or IV until consuming a consistently balanced and nutritious diet.
- Toxic: There is no defined upper limit (UL) for thiamine because of its relative safety.
Pediatric (<18 years)
Supplemental/Maintenance:
- Infants: 0.3 to 0.5 mg/day
- Children: 0.5 to 1 mg/day
Pharmacologic/Therapeutic, for thiamine deficiency (beriberi): 10 to 25 mg per dose, IM or IV, daily (if critically ill), or 10 to 50 mg per dose orally every day for 2 weeks, then 5 to 10 mg per dose orally daily for 1 month.
- Toxic: No toxic intake level known to date.
Overview
Thiamine is generally considered virtually nontoxic, even in very high doses orally. Being water soluble, thiamine excretion is rapid; the vitamin is not stored in the body, and accumulation to toxic levels is highly improbable using oral intake. No adverse effects associated with thiamine intake from food sources or nutritional supplements have been reported. Rare occurrences of adverse effects of thiamine have been documented, although they appear to be largely associated with allergic reactions to thiamine injections.
Nutrient Adverse Effects
General Adverse Effects
Adverse effects are theoretically possible but rare with oral supplemental thiamine intake. Oral doses greater than 200 mg have been reported to cause drowsiness in some individuals. In a study of 989 patients, 100 mg/day IV thiamine hydrochloride resulted in a burning effect at the injection site in 11 subjects and pruritus in one.
Large doses of vitamin B1over an extended period may cause imbalance among various B vitamins.
Administration of IV or IM thiamine warrants caution because anaphylactic or allergic reaction infrequently occurs. Allergic reactions to thiamine injections are rare (<1%) but can be severe and include cardiovascular collapse and death, angioedema, paresthesia, warmth, and rash.
Adverse Effects Among Specific Populations
High oral intakes might have some unknown potential for adverse reactions in select, metabolically compromised populations because of pharmacogenomic susceptibility, but such data are only recently under consideration.
Pregnancy and Nursing
A review of the medical literature reveals no substantial reports of adverse effects related to fetal development during pregnancy or to breast-fed infants.
Infants and Children
A review of the medical literature reveals no substantial reports of adverse effects specifically related to the use of thiamine in infants and children.
Contraindications
No contraindications are known to date, except hypersensitivity to thiamine or to any component of any compound formulation. Some clinicians and researchers are proposing that cancer patients undergoing chemotherapy may benefit from restricted thiamine intake during treatment.
Precautions and Warnings
Use with caution with parenteral administration, especially with IV administration.
Laboratory Values
Whole-blood thiamine: Level less than 70 nmol/L indicates deficiency.
Erythrocyte transketolase (EKTA): Low activity of EKTA (<5 U/mmol hemoglobin) indicates deficiency, as does increase in EKTA (>16 U/mmol) after stimulation by the addition of TPP.
Therapeutic reference range: 1.6-4.0 mg/dL.
Strategic Considerations
Thiamine plays a critical role in a range of metabolic processes, especially the Krebs cycle and adenosine triphosphate (ATP) synthesis. Vitamin B1depletion by diet, lifestyle, or medications increases several risk factors, especially for the cardiovascular and nervous systems. Although thiamine is central to metabolic vitality and cardiovascular health, the use of loop diuretics increases the risk of clinically significant thiamine depletion. However, adverse effects caused by drug depletion can be safely and effectively treated with thiamine supplementation, while further supporting healthy cardiac function. Thiamine intake during chemotherapy is challenging, and personalized integrative care may clarify paradoxical data. In other, simpler situations, the potential for adverse effects from unintentional depletion of thiamine by pharmacological agents can be corrected through supplementation at typical therapeutic levels.
Aluminum carbonate gel (Basajel), aluminum hydroxide (Alternagel, Amphojel); combination drugs: aluminum hydroxide, magnesium carbonate, alginic acid, and sodium bicarbonate (Gaviscon Extra Strength Tablets, Gaviscon Regular Strength Liquid, Gaviscon Extra Strength Liquid); aluminum hydroxide and magnesium hydroxide (Advanced Formula Di-Gel Tablets, co-magaldrox, Di-Gel, Gelusil, Maalox, Maalox Plus, Mylanta, Wingel); aluminum hydroxide, magnesium trisilicate, alginic acid, and sodium bicarbonate (Alenic Alka, Gaviscon Regular Strength Tablets); calcium carbonate (Titralac, Tums), magnesium hydroxide (Phillips’ Milk of Magnesia MOM); combination drugs: magnesium hydroxide and calcium carbonate (Calcium Rich Rolaids); magnesium hydroxide, aluminum hydroxide, calcium carbonate, and simethicone (Tempo Tablets); magnesium trisilicate and aluminum hydroxide (Adcomag trisil, Foamicon); magnesium trisilicate, alginic acid, and sodium bicarbonate (Alenic Alka, Gaviscon Regular Strength Tablets); combination drug: sodium bicarbonate, aspirin, and citric acid (Alka-Seltzer). | | Drug-Induced Nutrient Depletion, Supplementation Therapeutic, Not Requiring Professional Management |
Probability:
3. PossibleEvidence Base:
PreliminaryEffect and Mechanism of Action
Antacids interfere with the absorption of many nutrients, including thiamine. Thiamine is alkali reactive in solution and stabilized by acid. Thiamine absorption in the human small intestinal brush-border membrane vesicle is pH dependent. In particular, aluminum-based antacids may lower thiamine absorption.
Report
Majoor and de Vries described a patient who developed cardiac beriberi with polyneuritis after chronic use of large amounts of magnesium trisilicate.
Nutritional Therapeutics, Clinical Concerns, and Adaptations
The adverse effect on absorption of thiamine can be reduced by separating antacid use by at least 2 hours from intake of thiamine supplements or foods relied on as primary thiamine dietary sources.
- Aminoglycoside antibiotics:Amikacin (Amikin), gentamicin (G-mycin, Garamycin, Jenamicin), kanamycin (Kantrex), neomycin (Mycifradin, Myciguent, Neo-Fradin, NeoTab, Nivemycin), netilmicin (Netromycin), paromomycin (monomycin; Humatin), streptomycin, tobramycin (AKTob, Nebcin, TOBI, TOBI Solution, TobraDex, Tobrex).
- Beta-lactam antibiotics:Methicillin (Staphcillin); aztreonam (Azactam injection); carbapenem antibiotics: meropenem (Merrem I.V.); combination drug: imipenem and cilastatin (Primaxin I.M., Primaxin I.V.); penicillin antibiotics: amoxicillin (Amoxicot, Amoxil, Moxilin, Trimox, Wymox); combination drug: amoxicillin and clavulanic acid (Augmentin, Augmentin XR, Clavulin); ampicillin (Amficot, Omnipen, Principen, Totacillin); combination drug: ampicillin and sulbactam (Unisyn); bacampicillin (Spectrobid), carbenicillin (Geocillin), cloxacillin (Cloxapen), dicloxacillin (Dynapen, Dycill), mezlocillin (Mezlin), nafcillin (Unipen), oxacillin (Bactocill), penicillin G (Bicillin C-R, Bicillin L-A, Pfizerpen, Truxcillin), penicillin V (Beepen-VK, Betapen-VK, Ledercillin VK, Pen-Vee K, Robicillin VK, Suspen, Truxcillin VK, V-Cillin K, Veetids), piperacillin (Pipracil); combination drug: piperacillin and tazobactam (Zosyn); ticarcillin (Ticar); combination drug: ticarcillin and clavulanate (Timentin).
- Cephalosporin antibiotics:Cefaclor (Ceclor), cefadroxil (Duricef), cefamandole (Mandol), cefazolin (Ancef, Kefzol), cefdinir (Omnicef), cefepime (Maxipime), cefixime (Suprax), cefoperazone (Cefobid), cefotaxime (Claforan), cefotetan (Cefotan), cefoxitin (Mefoxin), cefpodoxime (Vantin), cefprozil (Cefzil), ceftazidime (Ceptaz, Fortaz, Tazicef, Tazidime), ceftibuten (Cedax), ceftizoxime (Cefizox), ceftriaxone (Rocephin), cefuroxime (Ceftin, Kefurox, Zinacef), cephalexin (Keflex, Keftab), cephapirin (Cefadyl), cephradine (Anspor, Velocef), imipenem combination drug: imipenem and cilastatin (Primaxin I.M., Primaxin I.V.); loracarbef (Lorabid), meropenem (Merrem I.V.).
- Fluoroquinolone (4-Quinolone) antibiotics:Cinoxacin (Cinobac, Pulvules), ciprofloxacin (Ciloxan, Cipro), enoxacin (Penetrex), gatifloxacin (Tequin), levofloxacin (Levaquin), lomefloxacin (Maxaquin), moxifloxacin (Avelox), nalidixic acid (Neggram), norfloxacin (Noroxin), ofloxacin (Floxin, Ocuflox), sparfloxacin (Zagam), trovafloxacin (alatrofloxacin; Trovan).
- Macrolide antibiotics:Azithromycin (Zithromax), clarithromycin (Biaxin), dirithromycin (Dynabac), erythromycin oral (EES, EryPed, Ery-Tab, PCE Dispertab, Pediazole), troleandomycin (Tao).
- Sulfonamide antibiotics:Sodium sulfacetamide (AK-Sulf, Bleph-10, Sodium Sulamyd), sulfamethoxazole (Gantanol), sulfanilamide (AVC), sulfasalazine (salazosulfapyridine, salicylazosulfapyridine, suphasalazine; Apo-Sulfasalazine, Azulfidine, Azulfidine EN-Tabs, PMS-Sulfasalazine, Salazopyrin, Salazopyrin EN-Tabs, SAS), sulfisoxazole (Gantrisin); combination drug: sulfamethoxazole and trimethoprim (cotrimoxazole, co-trimoxazole, SXT, TMP-SMX, TMP-sulfa; Bactrim, Bactrim DS, Cotrim, Septra, Septra DS, Sulfatrim, Uroplus); triple sulfa (Sultrin Triple Sulfa).
- Chemotherapy, cytotoxic antibiotics:Bleomycin (Blenoxane), dactinomycin (Actinomycin D, Cosmegen, Cosmegen Lyovac), mitomycin (Mutamycin), plicamycin (Mithracin).
- Miscellaneous antibiotics:Bacitracin (Caci-IM), chloramphenicol (Chloromycetin), chlorhexidine (Peridex), colistimethate (Coly-Mycin M), dapsone (DDS, diaminodiphenylsulphone; Aczone Gel, Avlosulfon), furazolidone (Furoxone), lincomycin (Lincocin), linezolid (Zyvox), nitrofurantoin (Macrobid, Macrodantin), oral clindamycin (Cleocin), trimethoprim (Proloprim, Trimpex), vancomycin (Vancocin).
See also Tetracycline later. | | Drug-Induced Nutrient Depletion, Supplementation Therapeutic, Not Requiring Professional Management |
Probability:
3. PossibleEvidence Base:
PreliminaryEffect and Mechanism of Action
The B vitamins, including thiamine, are produced in appreciable amounts by probiotic microorganisms as part of their synergistic role within the healthy intestinal microecology.
Research
Repeated or chronic use of antimicrobial agents can deplete or functionally eliminate these beneficial flora and contribute to depleted status of thiamine and other important nutrients.
Nutritional Therapeutics, Clinical Concerns, and Adaptations
The severity of disruption to the intestinal microecology will vary depending on many factors, including an individual's diet, medical history, health status, and co-morbid conditions. Potential adverse effects of antibiotics on thiamine status can be safely and effectively prevented or reversed through supplementation with thiamine and related nutrients at standard supplemental levels, along with replenishment of flora through consumption of high doses of vigorous and variegated probiotic microorganisms. Duration of such restorative nutritional therapy depends on the individual's health status as well as the dosage, duration, and type of antibiotic medications(s) being administered. Individuals not undergoing diuretic therapy, suffering from alcoholism, or characterized by other high-risk factors will generally not require, although they may benefit from, increased thiamine supplementation during or after a single course of antibiotics; a short course of probiotic therapy is still recommended as supportive in such circumstances.
- Evidence: Fluorouracil (5-FU; Adrucil, Efudex, Efudix, Fluoroplex).
- Extrapolated, based on similar properties: Agalsidase beta (Fabrazyme), capecitabine (Xeloda), cladribine (Leustatin), cytarabine (ara-C; Cytosar-U, DepoCyt, Tarabine PFS), floxuridine (FUDR), fludarabine (Fludara), gemcitabine (Gemzar), lometrexol (T64), mercaptopurine (6-mercaptopurine, 6-MP, NSC 755; Purinethol), methotrexate (Folex, Maxtrex, Rheumatrex), pentostatin (Nipent), pemetrexed (Alimta), raltitrexed (ZD-1694; Tomudex), thioguanine (6-thioguanine, 6-TG, 2-amino-6-mercaptopurine; Lanvis, Tabloid), ZD9331.
| | Drug-Induced Effect on Nutrient Function, Supplementation Contraindicated, Professional Management Appropriate | | Bimodal or Variable Interaction, with Professional Management | | Drug-Induced Adverse Effect on Nutrient Function, Coadministration Therapeutic, with Professional Management |
Probability:
3. ProbableEvidence Base:
EmergingEffect and Mechanism of Action
Fluorouracil is an antimetabolite of the pyrimidine analog type. In the form of its active metabolite, 5-FU inhibits the conversion of thiamine to TPP and inhibits DNA and RNA synthesis. The cofactor of transketolase, TPP promotes nucleic acid ribose synthesis and tumor cell proliferation through the nonoxidative transketolase (TK) pathway.
Research
The research on the role of thiamine during chemotherapy is complex and seemingly contradictory, but an emerging consensus may clarify clinical options for integrative therapies within a strategic framework. Thiamine deficiency frequently occurs in patients with advanced cancer, particularly within the context of drug-induced nutrient depletion, and therefore thiamine supplementation has often been used for nutritional support. In vitro research and clinical observations suggest that fluoropyrimidines may increase cellular thiamine metabolism and depletion. This has raised concern of possible thiamine deficiency and indicated a potential beneficial role for increased dietary intake and supplementation of thiamine. Lactic acidosis caused by thiamine deficiency is known to complicate chemotherapy and radiotherapy of malignant tumors. However, clinical and experimental data demonstrate both increased thiamine utilization by tumor cells and thiamine's interference with certain types of anti-neoplastic chemotherapy. In particular, metabolic control analyses predict that, by supporting a high rate of nucleic acid ribose synthesis, thiamine and other stimulators of transketolase enzyme synthesis contribute to tumor cell survival, chemotherapy resistance, and cancer cell proliferation. Both human and animal studies support these hypotheses.
Nutritional Therapeutics, Clinical Concerns, and Adaptations
Scientific research and clinical experience suggest that no static and generic protocol is possible for thiamine support or restriction in patients undergoing antineoplastic chemotherapy, especially involving 5-FU. Integrating the findings of the research literature into a clinical context requires an individualized and evolving approach to the therapeutic process, tactical emphases, and the patient's general health status. Ultimately, it is critical to determine whether the benefits of thiamine administration outweigh the risks of tumor proliferation and how such determination may shift through the course of treatment. Some researchers and clinicians have also suggested administration of transketolase inhibitors as a complementary tactic in treating some oncology patients. Thus, the evidence supports a flexible strategy involving phased restriction of thiamine intake during chemotherapy, followed by compensatory dietary enhancement and/or thiamine supplementation as a reasonable conservative approach, with the particulars of such implementation ultimately dependent on the prior history, emerging needs, and evolving response of the individual patient.
Intercurrent thiamine supplementation may be clinically appropriate for some patients at critical stages in their therapeutic regimen if thiamine depletion presents an overriding concern for patient survival and well-being. Implementation of such an approach to integrative personalized care requires active collaboration by health care professionals trained and experienced in both conventional pharmacology and nutritional therapeutics. When tumor-bearing patients receive thiamine-containing supplements, it would seem prudent to use RDA levels of thiamine (1-2 mg/day) and avoid higher doses (10-100 or more mg/day) of thiamine, unless the patient has cardiac, neurological, or musculoskeletal symptoms consistent with severe thiamine deficiency and promptly ameliorated by a therapeutic trial of higher-dose thiamine administration. Once corrected, a return to RDA-level supplementation and encouraging dietary intake of thiamine-rich foods, such as brewer's/nutritional yeast, would seem appropriate in view of the data on thiamine's potential to enhance tumor growth. In patients with recurrent or metastatic malignant disease, even with no evidence of tumor on scans and physical examination after treatment, micrometastatic disease is probable, and in the absence of a life-threatening deficiency syndrome, it would seem prudent to avoid high levels of thiamine administration (as well as niacin/niacinamide, shown to support growth of new blood vessels—angiogenesis—on which tumor growth and metastasis depend).
- Evidence: Furosemide (Lasix).
- Extrapolated, based on similar properties: Bumetanide (Bumex), ethacrynic acid (Edecrin), torsemide (Demadex).
| | Drug-Induced Nutrient Depletion, Supplementation Therapeutic, Not Requiring Professional Management | | Prevention or Reduction of Drug Adverse Effect | | Adverse Drug Effect on Nutritional Therapeutics, Strategic Concern |
Probability:
1. CertainEvidence Base:
ConsensusEffect and Mechanism of Action
Several studies have suggested that loop diuretics, especially furosemide (Lasix), can cause thiamine depletion due to increased urinary excretion, contributing to cardiac insufficiency in patients with CHF. Further research has indicated that the compromised thiamine status of individuals with CHF may be caused by altered metabolism, rather than simple deficiency, of thiamine. In a study of the diuretic effects of single IV doses of furosemide on six healthy volunteers, Rieck et al. observed a doubling of thiamine excretion rate, along with the expected increased urine volume and sodium excretion. Another study examined cardiac function and status of select nutrients in 30 patients with idiopathic dilated cardiomyopathy using diuretics, compared with a similar number of healthy control individuals. Measuring the activity of erythrocytic transketolase and the effect of TPP, da Cunha et al. determined the presence of thiamine deficiency in 33% of the patients with heart disease (vs. 10% of controls).
Even though all loop diuretics work by inhibiting sodium and chloride reabsorption in the thick ascending limb of Henle's loop, no conclusive research on the effects of other loop diuretics on thiamine has been published. However, CHF is characteristic of wet beriberi, caused by thiamine deficiency. Patients receiving furosemide are likely to have compromised kidney function, decreased metabolic function associated with aging, malnourishment, alcoholism and other lifestyle factors, and other variables aggravating thiamine depletion, deficiency, and dysregulation.
Research
As noted earlier, numerous studies have determined that thiamine depletion is a common phenomenon among patients undergoing loop diuretic therapy. For example, an investigation of 38 sequential patients in a cardiology clinic assessed thiamine status by in vitro erythrocyte transketolase activity assay and dietary intake of thiamine. Thiamine deficiency was found in 21% of the patients and evidence of risk for dietary thiamine inadequacy in 25%.
A small pilot study in 1991 examined the effects of long-term furosemide therapy (80-240 mg for 3-14 months) in hospitalized patients with CHF to determine the occurrence of clinically significant thiamine deficiency caused by urinary loss. Elevated levels of thiamine pyrophosphate effect (TPPE), indicating thiamine deficiency, were found in 21 of 23 furosemide-treated patients and in 2 of 16 age-matched controls. Biochemical evidence of thiamine deficiency tended to be more common among patients with poor left ventricular ejection fractions (LVEF). A 7-day course of IV thiamine, 100 mg twice daily, lowered TPPE levels to normal in six of the subjects, indicating normal thiamine utilization capacity, and improved LVEF in four of five patients, as demonstrated by echocardiography. These preliminary findings suggest that long-term furosemide therapy may be associated with clinically significant thiamine deficiency, presumed to result from urinary loss, and contribute to impaired cardiac performance in patients with CHF. Further, this apparent drug-induced depletion pattern responded to appropriate thiamine administration within an inpatient setting.
In 1995 the same research team conducted a double-blind, placebo-controlled trial in which they initially randomized 30 subjects to 1 week of either IV thiamine (200 mg/day) or placebo within inpatient care. In the second phase, all individuals were discharged and given oral thiamine (200 mg/day) for 6 weeks. After the initial IV thiamine, thiamine status normalized, and LVEF increased significantly in those who received IV thiamine, in contrast to no measurable response in thiamine status among those given IV placebo. After the 7-week intervention, the 27 remaining subjects showed 22% improvement in LVEF. The researchers concluded that cardiac function in CHF patients may be exacerbated by thiamine depletion attributable to long-term furosemide therapy; thiamine supplementation or systematic dietary enhancement may avert or correct this adverse effect and its probable sequelae in patients with moderate to severe CHF.
Although there is consensus on an association between loop diuretic therapy and compromised thiamine status, conclusive evidence is lacking to confirm a consistent causal relationship. Using high-pressure liquid chromatography (HPLC) to assess blood thiamine and thiamine ester concentrations in erythrocytes of 41 elderly patients with CHF treated with furosemide (and a control group), a Swedish team found reduced thiamine diphosphate (TPP), the storage form of thiamine, but not thiamine phosphate (TP). The researchers concluded that the observed change in CHF patients taking furosemide was most likely not an expression of a thiamine deficiency, but rather of altered thiamine metabolism not yet explained.
Zenuk et al. investigated the thiamine status of 32 patients with CHF who received either 40 to 80 mg or 80 mg or more of furosemide daily. Using erythrocyte transketolase enzyme activity and the degree of TPPE, these researchers found that 96% (24 of 25) of those receiving the higher diuretic dose demonstrated biochemical evidence of severe thiamine deficiency, as did 57% (4 of 7) of patients taking 40 mg furosemide daily. No other clinical variables showed a significant association with thiamine status.
Thus, collectively, the body of evidence suggests that thiamine deficiency occurs in a substantial proportion of CHF patients being treated with furosemide.
Nutritional Therapeutics, Clinical Concerns, and Adaptations
Long-term diuretic administration remains a central pharmacological therapy of heart insufficiency and hypertension in conventional practice. However, loop diuretics can aggravate the high-risk status inherent to many conditions for which these medications are prescribed, especially among hospitalized or chronic care elderly patients. Thiamine supplements should be considered in patients undergoing sustained diuresis, particularly when dietary deficiency may be present. Investigating the risk posed by diuretic use for subclinical thiamine deficiency in elderly patients, Swiss researchers suggested that low-dose thiamine supplementation may help prevent the development of subclinical wet beriberi in such patients. Pending conclusive evidence to the contrary, patients taking furosemide, and possibly other loop diuretics, would most likely benefit from thiamine support of 100 mg per day, orally.
- Evidence: Nortriptyline (Aventyl, Pamelor).
- Extrapolated, based on similar properties: Amitriptyline (Elavil); combination drug: amitriptyline and perphenazine (Triavil, Etrafon, Triptazine); amoxapine (Asendin), clomipramine (Anafranil), desipramine (Norpramin, Pertofrane), doxepin (Adapin, Sinequan), imipramine (Janimine, Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), trimipramine (Surmontil).
| | Drug-Induced Nutrient Depletion, Supplementation Therapeutic, Not Requiring Professional Management | | Beneficial or Supportive Interaction, Not Requiring Professional Management |
Probability:
3. PossibleEvidence Base:
PreliminaryEffect and Mechanism of Action
The mechanism of action involved in the proposed interactions between nortriptyline and thiamine, or more exactly B-vitamin complex, is uncertain at this time, and various explanations are available. Interference with nutrient metabolism of other drug-induced depletion effects may be corrected by supplementation. A synergistic interaction between the antidepressant and the nutrient(s) may also be contributing to improved outcome measures. Further research to determine the mechanism(s) of action could clarify the physiological processes and help refine integrative therapies to enhance clinical outcomes.
Research
A 1992 study involving 14 institutionalized geriatric patients with impaired cognitive function undergoing treatment for depression is the primary evidence for augmentation of nortriptyline therapy using supplemental B-vitamin complex. In this 4-week, randomized, placebo-controlled, double-blind trial, the elderly inpatients were administered open tricyclic antidepressant (TCA) treatment (nortriptyline titrated to doses yielding blood levels of 50-150 ng/mL) along with vitamins B 1 , B 2 , and B 6 (each 10 mg/day). The researchers reported that “the active vitamin group demonstrated significantly better B 2 and B 6 status on enzyme activity coefficients and trends toward greater improvement in scores on ratings of depression and cognitive function, as well as in serum nortriptyline levels compared with placebo-treated subjects.”
Nutritional Therapeutics, Clinical Concerns, and Adaptations
The coadministration of thiamine, as part of a B-vitamin complex formula at customary dosage levels, offers reasonable potential for enhancing treatment of depression (especially with cognitive dysfunction) with nortriptyline, or other TCAs, particularly in elderly of other patients who have restricted mobility or who are living in institutionalized care settings, at increased risk of inadequate and inconsistent nutrient intake.
Ethinyl estradiol and desogestrel (Desogen, Ortho-TriCyclen). Ethinyl estradiol and ethynodiol (Demulen 1/35, Demulen 1/50, Nelulen 1/25, Nelulen 1/50, Zovia). Ethinyl estradiol and levonorgestrel (Alesse, Levlen, Levlite, Levora 0.15/30, Nordette, Tri-Levlen, Triphasil, Trivora). Ethinyl estradiol and norethindrone/norethisterone (Brevicon, Estrostep, Genora 1/35, GenCep. 1/35, Jenest-28, Loestrin 1.5/30, Loestrin1/20, Modicon, Necon 1/25, Necon 10/11, Necon 0.5/30, Necon 1/50, Nelova 1/35, Nelova 10/11, Norinyl 1/35, Norlestin 1/50, Ortho Novum 1/35, Ortho Novum 10/11, Ortho Novum 7/7/7, Ovcon-35, Ovcon-50, Tri-Norinyl, Trinovum). Ethinyl estradiol and norgestrel (Lo/Ovral, Ovral). Mestranol and norethindrone (Genora 1/50, Nelova 1/50, Norethin 1/50, Ortho-Novum 1/50). Related, internal application: Etonogestrel/ethinyl estradiol vaginal ring (Nuvaring). | | Drug-Induced Nutrient Depletion, Supplementation Therapeutic, Not Requiring Professional Management | | Prevention or Reduction of Drug Adverse Effect |
Probability:
2. ProbableEvidence Base:
EmergingEffect and Mechanism of Action
The use of oral contraceptives (OCs) may be associated with altered metabolism of many nutrients and increased susceptibility to depletion in some women, particularly vitamins B 1 , B 2 , B 3 , B 6 , B 12 , and C, as well as folic acid, manganese, magnesium, and zinc.
Research
Researchers have observed slight to moderate decreases in thiamine levels in some women taking OCs. Evidence is still insufficient to confirm consistent patterns of nutritional deficiencies resulting from OC. Although thiamine levels have not been consistently lower in women taking OCs compared with controls, urinary thiamine levels are higher in women using OCs who also take supplemental thiamine.
Nutritional Therapeutics, Clinical Concerns, and Adaptations
The clinical implications of this probable interaction are uncertain at this time. Further research focusing on variable susceptibility to thiamine depletion, particularly such factors as pharmacogenomic variables, dietary intake, age, and concomitant medications and health conditions, could further define conditions of increased risk and elucidate approaches for optimal correction with nutritional therapies. Pending such evidence, coadministration with customary supplemental daily doses of thiamine, particularly in a B-complex formulation to address parallel depletion effects, would safely and effectively reduce risks of adverse effects.
- Evidence: Phenytoin (diphenylhydantoin; Dilantin, Phenytek).
- Extrapolated, based on similar properties: Carbamazepine (Carbatrol, Tegretol), clonazepam (Klonopin), clorazepate (Tranxene), divalproex semisodium, divalproex sodium (Depakote), ethosuximide (Zarontin), ethotoin (Peganone), felbamate (Felbatol), fosphenytoin (Cerebyx, Mesantoin), levetiracetam (Keppra), mephenytoin, mephobarbital (Mebaral), methsuximide (Celontin), oxcarbazepine (GP 47680, oxycarbamazepine; Trileptal), phenobarbital (phenobarbitone; Luminal, Solfoton), piracetam (Nootropyl), primidone (Mysoline), sodium valproate (Depacon), topiramate (Topamax), trimethadione (Tridione), valproate semisodium, valproic acid (Depakene, Depakene Syrup), vigabatrin (Sabril), zonisamide (Zonegran).
| | Drug-Induced Nutrient Depletion, Supplementation Therapeutic, Not Requiring Professional Management | | Prevention or Reduction of Drug Adverse Effect |
Probability:
1. CertainEvidence Base:
AMPERSANDthinsp; AMPERSANDthinsp; ConsensusEffect and Mechanism of Action
In their study of phenytoin's effects on the in vivo kinetics of thiamine in rat nervous tissues, Patrini et al. reported that phenytoin appeared to interfere mainly with thiamine and thiamine monophosphate (TMP) uptake, thiamine pyrophosphate (TPP) dephosphorylation to TMP, and TPP turnover times, and that these effects were particularly prominent in the cerebellum and brainstem of chronically treated animals.
Research
The research team led by M.I. Botez in Montreal has contributed significantly to our understanding of the effects of phenytoin on thiamine in humans. In a 1982 study, Botez et al. determined by microbiological assay a statistically significant difference between whole-blood thiamine and cerebrospinal fluid (CSF) thiamine levels in comparing samples from 23 control subjects and 11 phenytoin-treated epileptic patients. Similar studies of 157 epileptic patients observed low levels of folate and thiamine in the blood and CSF, associated with phenytoin therapy. In a subsequent clinical trial this research team conducted a clinical trial investigating the effects of thiamine and folate on verbal and nonverbal intelligence quotient (IQ) testing in 72 epileptic patients receiving phenytoin alone or in combination with phenobarbital for more than 4 years. They noted that 31% had subnormal blood thiamine levels and 30% had low folate at baseline assessment, and that such vitamin deficiencies were independent phenomena. After a 6-month, randomized, double blind trial, they found that thiamine (50 mg/day) improved neuropsychological functions in both verbal and nonverbal IQ testing. In particular, higher scores were recorded on the block design, digit symbol, similarities, and digit span subtests. The researchers concluded that, in epileptic patients chronically treated with phenytoin, thiamine supplementation improves neuropsychological functions, such as visuospatial analysis, visuomotor speed, and verbal abstracting ability.
Nutritional Therapeutics, Clinical Concerns, and Adaptations
Individuals undergoing anticonvulsant therapy, particularly using phenytoin, will most likely benefit from coadministration of 50 to 100 mg of oral thiamine daily. Such corrective nutrient therapy seems prudent, especially given that vitamin B 1 has no known toxicity. All currently available evidence indicates that such coadministration is safe and can be undertaken without close supervision or specific monitoring. Nevertheless, individuals using any anticonvulsant medication should consult with their prescribing physician and a health care professional experienced in nutritional therapeutics before introducing any significant levels of supplementation into their therapeutic regimen.
| | Beneficial or Supportive Interaction, with Professional Management | | Prevention or Reduction of Drug Adverse Effect |
Probability:
2. ProbableEvidence Base:
PreliminaryEffect and Mechanism of Action
Thiamine is involved in the presynaptic release of acetylcholine and exerts a cholinomimetic effect in the central nervous system. Thiamine binds to nicotinic receptors and may exhibit anticholinesterase activity. Scopolamine exerts an anticholinergic effect.
Research
A small human study investigated the effects of pharmacological doses of thiamine on the cognitive deficits typically associated with scopolamine therapy. In this randomized, double-blind, placebo-controlled, double-crossover clinical trial with 13 healthy subjects, the group receiving 5 g thiamine orally (with scopolamine, 0.007 mg/kg IM) demonstrated significantly reduced adverse effects of scopolamine compared with the placebo group. Improvements were measured in P3 latency, spectral components of electroencephalography, and memory recall.
Nutritional Therapeutics, Clinical Concerns, and Adaptations
Patients undergoing scopolamine therapy will most likely benefit from oral thiamine coadministration, generally 2 to 4 g/day. Such supportive nutrient therapy probably will have significant clinical benefit and generally is considered to present negligible risk. The available research has been conducted with higher doses and close supervision (in a research setting with healthy patients). Pending further research into specific doses and response patterns with patient populations prescribed scopolamine for typical medical conditions, close supervision and regular monitoring are advisable, preferably within an integrative care setting providing for collaboration between the prescribing physician and a health care professional experienced in nutritional therapeutics.
- Evidence: Stavudine (d4T, Zerit).
- Extrapolated, based on similar properties: Abacavir (Ziagen), didanosine (ddI, dideoxyinosine; Videx); dideoxycytidine (ddC, zalcitabine; Hivid), lamivudine (3TC, Epivir), stavudine (D4T; Zerit), tenofovir (Viread), zidovudine (azidothymidine, AZT, ZDV, zidothymidine; Retrovir); combination drugs: zidovudine and lamivudine (Combivir); abacavir, lamivudine, and zidovudine (Trizivir).
| | Drug-Induced Nutrient Depletion, Supplementation Therapeutic, Not Requiring Professional Management | | Prevention or Reduction of Drug Adverse Effect |
Probability:
3. PossibleEvidence Base:
PreliminaryEffect and Mechanism of Action
With expanded use of stavudine and similar medications, often with highly active antiretroviral therapy (HAART) protocols, severe lactic acidosis has been increasingly reported as a severe and potentially fatal complication of HIV treatment. Defects in the gene on the X chromosome encoding the E1 peptide of the E1 subunit (pyruvate decarboxylase), which binds TPP, can contribute to increased susceptibility to lethal lactic acidosis.
Reports
Two case reports provide the evidence supporting thiamine therapy to reduce risk of or respond to adverse effects of stavudine. Schramm et al. reported the case of a 30-year-old woman with AIDS and nucleoside analog–induced lactic acidosis that exacerbated shortly after introducing total parenteral nutrition and reversed within hours after treatment with IV thiamine. A 2001 paper described an asymptomatic HIV-infected woman treated with HAART (stavudine, lamivudine, and indinavir) for 1 year who demonstrated an “impressively rapid response (within a few hours)” to 100 mg IV thiamine.
Preexisting vitamin deficiency appears to be an important cofactor in the susceptibility to this unpredictable adverse reaction to therapy in patients with HIV infection.
Nutritional Therapeutics, Clinical Concerns, and Adaptations
Lactic acidosis induced by stavudine or similar nucleoside analog medications for HIV infection is a serious and often life-threatening condition, and such patients are usually already hospitalized or under close supervision by their prescribing physician. The available reports involved critical care and physician administration of high-dose thiamine to address both the lactic acidosis and the patient's presumed background vitamin deficiency status. The clinicians submitting these reports recommended that physicians prescribing stavudine therapy take note of the rapid response to thiamine administration, suggest that high-dose B vitamins should be given to any patient presenting with lactic acidosis under nucleoside analog treatment, and advise thiamine infusion for critical care of this potentially life-threatening complication of HIV therapy.
Supplementation with customary oral doses of a B-vitamin complex may be self-administered as a prophylactic measure by patients undergoing stavudine or other antiretroviral therapy, particularly when nutrient intake has been compromised by an inadequate or imbalanced diet. Pending further research into preventive and reactive doses of thiamine with respective modes of administration, for coadministration with stavudine or similar nucleoside analog medications, close supervision and regular monitoring are advisable when lactic acidosis is present or threatening, preferably within an integrative care setting providing for collaboration between the prescribing physician and a health care professional experienced in nutritional therapeutics.
- Evidence: Tetracycline (Achromycin, Actisite, Apo-Tetra, Economycin, Novo-Tetra, Nu-Tetra, Sumycin, Tetrachel, Tetracyn).
- Extrapolated, based on similar properties: Demeclocycline (Declomycin), doxycycline (Atridox, Doryx, Doxy, Monodox, Periostat, Vibramycin, Vibra-Tabs), minocycline (Dynacin, Minocin, Vectrin), oxytetracycline (Terramycin), tetracycline combination drugs: chlortetracycline, demeclocycline, and tetracycline (Deteclo); bismuth, metronidazole, and tetracycline (Helidac).
| | Impaired Drug Absorption and Bioavailability, Precautions Appropriate |
Probability:
3. PossibleEvidence Base:
PreliminaryEffect and Mechanism of Action
Nutrient formulations containing B vitamins, including thiamine (B 1 ), may interfere with tetracycline pharmacokinetics.
Research
In an investigation of the effects of various nutrients on the pharmacokinetics of tetracycline hydrochloride in healthy subjects, researchers observed a significant impairment of drug bioavailability associated with concomitant oral administration of a B-complex vitamin formulation.
Clinical Implications and Adaptations
Physicians prescribing tetracycline or related antibiotic medications should advise patients regularly supplementing with thiamine, alone or within a B-complex vitamin formulation, to take the nutrient(s) and the medication at least 4 hours apart from each other.
Thiaminasesare thiamine antagonists found in a few plants and some raw seafood. When these enzymes are ingested, in coffee, black tea, certain vegetables, and the raw flesh and viscera of certain fish and shellfish, especially carp, they can destroy dietary or supplemental thiamine. Such type I thiaminases render thiamine biologically inactive by displacing its pyrimidine methylene group with a nitrogenous base or SH-compound to eliminate the thiazole ring. Once the thiamine molecule is cleaved by a thiaminase, the body is incapable of restoring it. Thus, the ingestion of significant amounts of thiaminases can induce thiamine deficiency, even when dietary intake of thiamine may be otherwise adequate. The level of raw fish consumption by humans is rarely sufficient, even among frequent sushi eaters, to constitute a significant probability of clinically significant thiamine depletion. Thiaminases are denatured by heat, so cooking or other forms of heat treatment will render them inactive.
Chlorinated water tends to destroy thiamine, especially when heated in the cooking of grains. Chlorogenic acid, found both in decaffeinated and caffeinated coffee, also destroys thiamine.
Thiamine works synergistically with vitamin B 2 and vitamin B 3 .
Ames et al. suggest that combination therapy with thiamine, alpha lipoic acid, riboflavin, nicotinamide, and adequate potassium may be optimal for the initial treatment of patients with maple syrup urine disease, a rare, autosomal recessive disorder of branched-chain amino acid metabolism.
Horsetail
(Equisetum arvense)Equisetum arvense(horsetail) may impair thiamine absorption. This particular form of thiaminase poisoning occurs most often among farm animals where hay has been contaminated by horsetail. No cases have been reported of humans consuming Equisetummedicinally and experiencing clinically significant thiamine depletion or deficiency.
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