Pain & Circulatory Therapy

CLINICAL BENEFITS

• Safe, effective, non-invasive and user-friendly reimbursable treatment

• Minimal potential for side effects, easily avoided

• Extremely high patient compliance, outcome and satisfaction

• Substantial reduction in out-bound patient referrals

FDA CLINICAL INDICATIONS

• Temporary increase in local blood circulation

• Temporary relief of minor muscle and joint aches, pains and stiffness

• Relaxation of muscles

• Muscle spasms

• Minor pain and stiffness associated with arthritis

Large Nerve & Small Nerve Fibers

What is in NutriNerve®?

A proprietary formulation that supports the body against neuropathy*

NutriNerve® SoftGel (1)

Alpha Lipoic Acid 150 mg

Gamma-Linolenic Acid (GLA) * 130 mg

Vitamin B-1 (Benfotiamine) 75 mg

Vitamin C 85 mg

Vitamin B-12 (Methylcobolim) 1 mg

Vitamin D (Cholecalciferol) 500IU

*GLA is the active ingredient derived from Borage Oil

Prescription Information:

Take 4 capsules per day. Two (2) in the morning and two (2) in the evening, preferably with meals. Four to six months of uninterrupted use is necessary to see the full benefit.

Precautions:

Some patients may experience an upset stomach and diarrhea in doses that equal or exceed six (6) capsules in a 24-hour period. There are no known issues with renal insufficiency.

Statement of Use and Treatment Program:

The ingredients in NutriNerve® have been shown to improve neuropathy symptoms by improving underlying physiology*. This goes beyond simply relieving symptoms, such as pain. Please visit www.nutrinerve.com for more peer-reviewed references.

Medical Advisors:

Dr. Aaron Vinik, MD, PhD, FCP, MACP, FACE

Director of Research and the Neuroendocrine Unit, Eastern Virginia

Medical School, Norfolk, VA

Prof. Dr. Med. Dan Ziegler, MD, FRCP

German Diabetes Center, Heinrich Heine University

Düsseldorf, Germany

Ingredient Summary

Alpha Lipoic Acid (ALA) has been shown in placebo-controlled randomized studies to improve diabetic neuropathy symptoms. In the SYDNEY 2 trial, there was demonstrated to be a 52% decrease in Total Symptom Score (including stabbing pain, burning pain, paresthesia, and asleep numbness of the feet) after five weeks of 600 mg ALA.i ALA is also attributed with a 44% increase in vasodialation of the brachial artery.ii Gamma Linolenic Acid (GLA) has been shown to restore nerve conduction velocity in animals that have had a 25% decrease in nerve conduction velocity due to diabetes.iii

Benfotiamine (B-1) A statistically significant (p = 0.0287) improvement in the neuropathy score was observed in a group given benfotiamine.iv

Vitamin C is a powerful antioxidant and has been shown to improve endothelial function and nerve perfusion.v

Vitamin B-12 restores blood flow which produces myelin synthesis, a fatty substance that protects the nerve fibers.

Vitamin D specifically addresses the vitamin deficiency in type 1 and 2 diabetics. In an individual study has resulted in a very significant improvement in neuropathic symptoms.vi

2007 ADA Scientific Session – Oral Presentation

Effect of 4-Year Antioxidant Treatment with Alpha-Lipoic Acid in Diabetic

Polyneuropathy: The NATHAN 1 Trial

Results:

The aim of this study was to evaluate the efficacy and safety of [alpha]-lipoic acid over 4 years in diabetic patients with mild to moderate distal symmetric polyneuropathy (DSP). In this multicenter, randomized, double-masked, parallel-group clinical trial 460 diabetic patients with stage 1 or stage 2a DSP were randomly assigned to oral treatment with [alpha]-lipoic acid 600 mg qd (ALA; n=233) or placebo (n=227) for 4 years following a 6-week placebo run-in phase. Outcome measures included: Primary outcome measure was a composite score of including the Neuropathy Impairment (NIS) Score of the lower limbs and 7 nerve function tests (NIS[LL]+7 tests; a ). Secondary outcome measures included the Total Symptom Score (TSS); nerve symptom change), Neuropathy Symptoms and Change (NSC), NIS, NIS[LL], individual NIS components, motor and sensory nerve conduction attributes, and quantitative sensory testing (QST). Data analysis was based on the intention to treat. The demographic variables and the outcome measures at baseline were comparable between the groups as were the HbA1c levels during follow-up. The NIS[LL]+7 tests composite score improved after 4 years vs. baseline by 0.45 ± [plusmn]0.37 (mean±[plusmn]SEM) in the ALA group and worsened by 0.34 ± [plusmn]0.35 points in the placebo group (p=0.105). The NIS and NIS[LL] improved by 0.68 ± [plusmn]0.44 and 0.34 ± [plusmn]0.30 points on ALA and worsened by 0.61 ± [plusmn]0.46 and 0.43 ± [plusmn]0.31 points on placebo, respectively (p=0.028 and p=0.051). The NIS[LL] muscular weakness subscore improved by 0.21[[±]plusmn]0.11 on ALA and deteriorated by 0.17 ± [plusmn]0.15 on placebo (p=0.045). The NSC score for weakness severity improved by 0.05 ± [plusmn]0.03 points on ALA and worsened by 0.04 ± [plusmn]0.03 points on placebo (p=0.008). No significant differences between both groups after 4 years were noted for the nerve conduction parameters and QST. The rates of adverse events were comparable between the groups during the study. In conclusion, 4-year treatment with [alpha]-lipoic acid in mild to moderate DSP is well tolerated and improves some neuropathic deficits and symptoms, but not nerve conduction.

(Endnotes)

i Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the

SYDNEY 2 trial.Diabetes Care. 2006 Nov;29(11):2365-70

ii Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study. Circulation. 2005 Jan 25;111(3):343-8. Epub 2005 Jan 17.

iii Beneficial effects of gamma-linolenic acid supplementation on nerve conduction velocity, Na+, K+ ATPase activity, and membrane fatty acid composition in the sciatic nerve of diabetic rats.J Nutr Biochem. 1999 Jul;10(7):411-20.

iv Benfotiamine in the treatment of diabetic polyneuropathy--a three-week randomized, controlled pilot study (BEDIP study). Int J Clin Pharmacol Ther. 2005 Feb;43(2):71-7.

v Lipid independent effects of statins on endothelial function and bioavailability of nitric oxide in hypercholesterolemic patients Am Heart Journal 2005; 149, 471

vi Repletion of vitamin D resulted in the symptoms of severe and disabling diabetic neuropathy being improved by correction of the vitamin D deficiency in an individual patient. Case in Endocrinology 2012; 165056

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.