Sublingual L-GSH Supplementation in Male Subjects With Smoking Habit and/or Hypertension

Summary

Background. The antioxidant systems are the main endogenous defense against free radicals, and glutathione seems to play an important role in this mechanism. Reduced glutathione enters into the detoxification processes of endogenous products, such as hydro- and lipoperoxides and exogenous compounds such as pollutants, heavy metals and some drugs. Changes in GSH homeostasis have been implicated in the etiology and progression of several diseases. Supplementation of GSH may improve the endogenous antioxidant defense and may contribute to decrease of oxidants tissue damage a pathophysiologic mechanism of many acute and chronic diseases.

However, the efficacy of GSH treatment seems to be closely related to the degree of its absorption and to the increase of its concentrations in plasma and cells. Previous studies of oral GSH administration in healthy volunteers or in patients failed to find any effect in terms of oxidative stress reduction and/or disease improvement because the GSH is quickly catabolized by gastrointestinal tract. We have recently observed (preliminary data) that a new sublingual formulation of L-GSH (OXITION), produced by PH\&T S.r.l., is able to increase erythrocyte and plasma GSH levels in healthy volunteers bypassing gastrointestinal barrier.

Objectives. The primary study objective is to determine whether medium term (4 weeks) of sublingual L-GSH supplementation to a population with smoking habit and/or arterial hypertension may result in improved endothelial function as assessed by the flow mediated dilation (FMD) technique versus placebo. FMD is a surrogate end point validated in the literature as prognostic predictor for major cardiovascular events in patients with endothelial dysfunction. Secondary study objectives are to determine differences between the 2 treatment in terms of oxidative stress markers.

Methods. This is a phase 3, double-blind, randomized, placebo-controlled, cross-over study performed in only one centre. Sixteen male subjects, aged ≥ 40 and ≤ 60 years, with smoking habit and/or hypertension defined as arterial blood pressure ≥ 140 and/or 90 mmHg or in anti-hypertensive treatment, will be enrolled and randomized to receive sublingual L-GSH (100 mg twice a day) or placebo according to a double-blind cross-over design for 4 weeks with a 3-week wash-out period between the two treatments. Baseline and at the end of each treatment period, FMD assessment and blood samples collection for routine (creatinine, urea, AST, ALT GGT, total cholesterol, HDL, LDL, triglycerides, fasting glucose) and specific (aminothiols, nitrotyrosine, malondialdehyde, 8-hydroxy-deoxyguanine) biochemical determination will be performed.

Conditions

• Health Subjects With Cardiovascular Risk Factors

Interventions

DIETARY_SUPPLEMENT

L-GSH

Reduced glutathione is formed by cysteine, glycine and glutamate. It enters into the detoxification processes of endogenous products, such as peroxides which are the final pathway of many reactions caused by cardiovascular risk factors. It also acts on the exogenous compounds, such as pollutants, heavy metals and some drugs.

DIETARY_SUPPLEMENT

Placebo

Placebo will be prepared using the same excipients of the dietary supplement without active substance.

Sponsors & Collaborators

• Niguarda Hospital

  lead OTHER

Principal Investigators

• Jonica Campolo, MSc · Insitute of Clinical Physiology CNR

• Gianpalolo Micheloni, MD · Niguarda Ca' Granda Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

40 Years

Max Age

60 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2014-02-28

Primary Completion

2014-05-31

Completion

2014-05-31

Countries

• Italy

Study Locations