Table 1.

Clinical trials in humans using phytate.

Year of Publication and Authors	Type of Clinical Trial	Studied Population	Phytate Formulation and Dose Administrated	Duration of the Intervention	Route of Phytate Administration	Outcomes	References
Perelló et al., 2018	Double-blind, randomized, placebo-controlled Phase I study	Healthy and hemodialysis patients	In healthy volunteers the dose was 0.5 mg/kg and ascended to 12.5 mg/kg. In hemodialysis patients was 9 mg/kg	28 days	Parenteral	Safety and tolerability, and lack of significant dialysability of IV SNF472.	[27]
Raggi et al., 2020	Double-blind, placebo-controlled Phase 2b trial	Hemodialysis patients	Patients were randomized 1:1:1 to SNF472 300 mg (n = 92), SNF472 600 mg (n = 91), or placebo (n = 91) by infusion in the hemodialysis lines thrice weekly during hemodialysis sessions	52 weeks	Parenteral	SNF472 significantly reduced the progression of coronary artery calcium and aortic valve calcification in patients receiving hemodialysis	[29]
Sanchis et al., 2018	Single-center, randomized, crossover, open-label study.	Patients living with type 2 diabetes	Diet plan with InsP6 supplementation (1 capsule of 380 mg of calcium–magnesium InsP6 thrice daily) or the same diet plan without IP6 supplementation.	48 weeks	Oral	InsP6 supplements for 3 months significantly reduced levels of circulating AGEs and HbA1c	[31]
Estruch et al., 2018	Multicenter trial randomly assigned (in a 1:1:1 ratio)	High cardiovascular risk patients without cardiovascular disease	A Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat.	Median follow-up of 4.8 years	Oral	Mediterranean diet supplemented with nuts (high phytate content) reduces the incidence of major cardiovascular events was lower compared to a reduced-fat diet.	[33]
Conte et al., 1999	Single center randomized trial.	Active calcium oxalate stone-formers.	Potassium citrate, phytate-rich dietary complement or placebo.	15 days	Oral	Reduction in the lithogen urinary risk	[48]
Guimerà et al., 2022	Single center randomized trial.	Patients with hypercalciuria (> 250 mg/24 h) and osteopenia or osteoporosis in the femur and/or spine (determined by densitometry)	1 capsule of 380 mg of calcium–magnesium InsP6 versus placebo.	12 weeks.	Oral	Phytate group had significantly lower calciuria and ß-Crosslaps levels.	[49]
Grases et al., 2009	Randomized, double-blind, three-period crossover clinical	Healthy dental plaque-forming volunteers	Control period (no mouthwash treat- ment), a placebo period (mouthwash with 0.001% zinc) and a phytate-treatment period (mouthwash with 0.001% zinc and 0.1% phytate).	3 weeks each period for 9 weeks total.	Topical mouthwash	High efficacy exhibited by phytate in reducing dental calculus formation.	[50]
Ikenaga et al., 2019	Randomized, double-blind placebo-controlled crossover study.	Asymptomatic hyperuricemic subjects	Placebo or InsP6 drinks (600 mg twice daily).	2 weeks	Oral	Significantly reduced uric acid levels in comparation with placebo.	[100]
Estruch et al., 2006	Substudy of a multicenter, randomized, primary prevention trial of cardiovascular disease.	Asymptomatic at high cardiovascular risk.	A Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat.	3 months	Oral	Improved fasting blood glucose, reduced blood pressure and increased HDL/cholesterol ratios in the high phytate diet in comparison with a low-fat diet.	[110]
Toobert et al., 2003	Randomized clinical trial	Postmenopausal women living with type 2 diabetes	Mediterranean Lifestyle Program (Mediterranean low-saturated fat diet, stress management training, exercise, group support, and smoking cessation) versus with usual care.	6 months duration	Oral	Reduction in HbA1c by the high phytate diet.	[111]
Elhayany et al., 2010	Prospective randomized clinical trial	Patients living with overweight and type 2 diabetes	A low carbohydrate Mediterranean, a traditional Mediterranean and the 2003 American Diabetic Association diet were compared.	12-month period	Oral	Both high phytate diets showed better weight loss effects and better reduction in HbA1c compared to other diet	[112]
Mirmiran et al., 2019	Randomized crossover clinical trial	Patients living with type 2 diabetes	Compared a legume-free diet or a legume-based diet.	8 weeks	Oral	Legumes (which are high in phytate) increased serum adiponectin concentrations	[113]
Lam et al., 2006	A phase I, open-label, multiple dose, dose-escalation clinical study	Smokers	A dose escalation study ranging from 12 to 30 g/d of myo-inositol for a month	1 month	Oral	Myo-Inositol in a daily dose of 18 g for 3 months is safe and well tolerated.	[178]
Lam et al., 2016	A randomized, double blind, placebo-controlled phase IIb study	Smokers with ≥1 site of dysplasia identified by autofluorescence bronchoscopy-directed biopsy	Placebo or myo-inositol 9 g once a day for 2 weeks, and then twice a day.	6 months	Oral	Reduction in progressive disease rates and IL-6 levels.	[169]
Bacic et al., 2010	Prospective, randomized, pilot clinical study.	Patients with invasive ductal breast cancer who received polychemotherapy.	InsP6 + Inositol (6 g) in comparation with placebo (vitamin C)	6 months	Oral	Significantly improved patients quality of life and protected patients from the reduction in the number of leukocytes and platelets.	[170]
Proietti et al., 2017	Double-blind and randomized controlled trial	Patients with breast cancer 6 weeks after lumpectomy.	4% topical skin formulation of InsP6 once a day versus placebo (gel containing hyaluronic acid).	6 months	Topical skin	Topical InsP6 significantly improved quality of life and functional status reducing side effects compared to control group. Moreover, white blood cells and platelets count values where higher in the treated group.	[171]
Sanchis et al., 2022	Randomized and crossover trial	Patients living with T2DM	1 capsule of 380 mg of calcium–magnesium InsP6 thrice daily	12 weeks	Oral	Significant decrease serum levels of HbA1c and increase adiponectin levels.	[114]