Stancioiu F, Mihai D, Papadakis GZ, Spandidos DA, Badiu C. Treatment for benign thyroid nodules with a combination of natural extracts. Mol Med Rep. 2019;20(3):2332-2338.
To determine whether a combination of spirulina, curcumin, and Boswellia reduces benign thyroid nodule size
Prospective, double-blind, placebo-controlled, cross-over clinical trial of 12 weeks duration
Placebo or a combination of spirulina (400 mg)/curcumin (50 mg)/Boswellia (50 mg) per capsule. No further information on extract form/strength is listed in the study. Dose was 2 capsules twice daily about 30 minutes before breakfast and lunch.
There were 34 participants; half (17) of the participants received active ingredients (AI), and half (17) received placebo (P).
Adult patients aged more than 18 years; euthyroid state (within normal limits: thyrotropin [TSH] and free thyroxine 4 [FT4]); no active dysfunctional thyroid disease; single benign thyroid nodule (between 2-5 cm) confirmed by fine-needle aspiration biopsy (FNAB); no previous thyroid surgery, thyroid ablation treatment, or substitution treatment with thyroid hormones; no steroid or beta-blocker treatment; presence of 1 or more thyroid nodules documented by ultrasound.
Age less than 18 years, diagnosis of suspicion of malignancy, Wilson’s disease, hypo/hyperthyroidism, contraception with an intrauterine device (IUD), acute infection, or known allergy to spirulina, curcumin, or Boswellia.
Study Parameters Assessed
The following parameters were assessed at 3 time points:
- Baseline (V1): Thyroid ultrasound (U/S) and TSH, FT4, and serum copper levels from blood draw.
- Week 6 (V2): 17 Patients previously on P received AI; 12 of the 17 patients previously on AI received P; and 5 randomly chosen AI patients stayed on AI. U/S and labs repeated.
- Week 12 (V3), which was the final visit with final U/S and blood draw: 17 patients had received P-AI, 12 patients had received AI-P, and 5 patients had received AI-AI. U/S and labs repeated.
Primary Outcome Measures
Primary Outcome: Change in size of the participant’s thyroid nodule, measuring both largest and smallest diameters at the same incident angle each time, and multiplying these to arrive at an estimation of area (Size=D x d).
Secondary outcome: Serum levels of TSH, FT4, and serum copper assessed to see whether any change occurred.
Primary outcome: Comparing the nodule area at each time point rendered an overall decrease; V1 was 4.38±3.14 cm2; V2 3.87±2.79 cm2; and V3 3.53±2.84 cm2 (P<0.04).
From the total of 34 subjects enrolled, 29 (85.29%) had a decrease in thyroid nodule size of 5% or more by end of study; 22 patients had decreases of 10% or more after 3 months. One patient had an insignificant decrease in nodule size, and 4 patients had increases in the size of their nodules.
In some scenarios, reducing benign thyroid nodules is important to avoid surgery, but there are several parameters that dictate this.
Statistical analysis showed that those on AI had a reduction of 0.611 cm2±0.933 (SD), but the authors list an N=39, though only 34 people finished the study. Placebo administration (n=29) had a mean decrease of 0.178 cm2±0.515 (SD). The reason for the 5 randomly chosen subjects not crossing over from AI to P was not explained and may have skewed the statistics and comparison between groups.
In some scenarios, reducing benign thyroid nodules is important to avoid surgery, but there are several parameters that dictate this. Most clinicians realize that until a nodule reaches certain criteria for surgery, they are generally monitored. The American Association of Clinical Endocrinology (AACE) guidelines1 for thyroid nodules divide them into 3 classes:
- Class 1—Low-risk thyroid lesion. Mostly cystic, isoechoic/spongiform nodules, regular halo.
- Class 2—Intermediate-risk thyroid lesion. Slightly hypoechoic nodules or isoechoic nodules with margins that are ovoid, round and smooth, or ill-defined; vascularization; rim calcifications; and hyperechoic spots.
- Class 3—High-risk thyroid lesions. Marked hypoechogenicity, microcalcifications, taller than wide, uneven margins, and evidence of extrathyroidal growth/adenopathy.
FNAB is recommended for high U/S–risk thyroid lesions >10 mm; intermediate US risk >20 mm; low US risk >20 mm and increasing in size.
This study suggests that using a spirulina/curcumin/Boswellia extract for 3 months may reduce the size of benign thyroid nodules. Unfortunately, the study was funded by a company that will be releasing this in a combination product in the future. Although apparently no researchers were associated with the company, the study was funded by said company; therefore, a certain bias may exist for positive results.
The precise formulation of the natural agents in the capsule was not clear in this study. Although spirulina is assumed to be a dried powder of the whole algae, there are many different types of curcumin and Boswellia extracts. The low dose used in this particular formula may be explained by the extraction process, the amount of active ingredients (eg, boswellic acids) or not. This study is difficult to repeat and validate without the specifics of the extractions used.
If reduction of thyroid nodules is a helpful, beneficial outcome, this study seems to indicate the study supplement was efficacious.