Interaction Between Levothyroxine and Probiotics in Hypothyroid Patients
Interaction Between Levothyroxine and Probiotics in Hypothyroid Patients
A prospective, randomized, single-blind, controlled, investigator-started clinical trial was
 carried out. Patients with primary hypothyroidism were randomly assigned to the study
 (VSL#3®+ LT4) and the control group (LT4). A two months treatment phase was followed by two
 months of follow-up. Clinical examination, blood tests for thyroid function and for
 peripheral tissue markers of thyroid hormones effect were performed monthly for 4 months. LT4
 dose adjustments were performed during the study when necessary.
Consecutive patients on LT4 replacement therapy attending the Endocrinology Unit of Modena
 (Italy) were screened. According to inclusion and exclusion criteria, eighty participants
 were enrolled and randomized in study or control group. The random allocation sequence was
 generated using 'Statistical Package for the Social Sciences' software for Macintosh (SPSS)
 considering a 1:1 ratio by the statistician of the Unit. Clinicians evaluating and enrolling
 patients were blinded to the randomization list. The study design provided a monthly visit
 for a 4 months overall time-frame. Patients assigned to the study group took the probiotic
 supplement VSL#3® for two months, followed by a two months period of follow-up. Study group
 patients were taught to assume the probiotic supplement at least two hours after LT4
 administration, to dissolve it in a cold beverage and to store it in a refrigerator (2°-8°C)
 in order to preserve bacteria load. The study design was single-blind since only the
 clinician was aware of the allocation. The VSL#3® administration was provided by nurses.
 Participants were invited to return all used and unused sachets to count the number of opened
 sachets per the number of treatment days.

 All patients underwent five visits (baseline, visit 1, 2, 3 and 4) in which anthropometrical
 evaluation (weight and height) and hormonal function assessment were performed. A blood
 sample was taken in the morning at each visit, on empty stomach and before LT4 ingestion. In
 occurrence of hormonal alteration, LT4 daily dose was adjusted according to clinical
 guidelines. At baseline, visit 2 and visit 4, patients underwent clinical examination with
 heart rate and blood pressure evaluation. During each visit, the following data were
 collected: probiotic assumption, sex, age, hypothyroidism aetiology, LT4 formulation dose and
 brand, body mass index (BMI), body surface area (BSA), systolic blood pressure, diastolic
 blood pressure, heart rate, TSH, fT4, fT3 and any possible LT4 posology adjustment. All the
 clinical data have been further databased.
Inclusion Criteria:

 -  primary hypothyroidism on LT4 replacement therapy

 -  TSH, fT3 and fT4 in the normal range

 -  stable LT4 dosage during the previous six months before enrolment

 -  Caucasian ethnicity

 Exclusion Criteria:

 -  total thyroidectomy for thyroid carcinoma

 -  high fiber diet

 -  intestinal malabsorption (e.g. bariatric surgery, inflammatory bowel diseases, coeliac
 disease)

 -  ongoing therapies interfering with LT4 absorption and/or metabolism (i.e.
 aluminium-containing antacids, sucralfate, proton pump inhibitors, calcium carbonate,
 raloxifene, bile acids sequestrants and ferrous sulfate)

 -  antibiotics treatment in the previous six months before enrolment