Multi-nutrient approach to nitric oxide production more efficient
than L-arginine alone
Sofi T, Juliano J, Ricciardi M
Introduction
This clinical study explores the notion that the failure of nutrient studies does not lie in the nutrient or nutrients themselves but in their lack of an efficacious delivery system. Just as free radicals require antioxidants to prevent oxidative stress, antioxidants require free radicals, in the form of nitric oxide, to ensure nutrient delivery. In natural foods they are always in close molecular association, so why not in scientifically inspired formulations?
Neurotransmitter based translational medicine adds “right delivery” to orthomolecular medicine, as conceived by Linus Pauling. Without right delivery, we have neither nutrient delivery nor therapeutic effect. Harnessing the body’s own intricate nutrient delivery network far exceeds anything we could manufacture.
Nitric Oxide (NO), synthesized from L-arginine by NO synthase, has numerous positive physiological actions in the cardiovascular, immune, and peripheral/central nervous systems. NO regulated circulation is the body’s premiere homeostatic nutrient delivery system, and is considered therapeutically significant when produced for 30 minutes or more. Prior to this study, no approach has produced more than 15 minutes of endogenous NO, challenging scientists to break this “15 minute threshold”. Prior to this study, a “bulldozer” approach (high doses of L-arginine) was used, risking oxidative stress, particularly among diabetic populations.
In this study, various nutrient delivery systems were tested until a therapeutic effect (30 minutes plus) was achieved using less than 1 gram of L-arginine per dose.
Materials and Methods
In this clinical study 50 human subjects ranging from 40 to 80 years of age, diagnosed with Nitric Oxide deficiency conditions to include hypertension and diabetes were used. Subjects were divided into 3 groups receiving either (a) placebo, (b) 1 gram L-arginine alone, or (c) multi-nutrient ADNO precursor formula Hemoxide containing significantly less than 1 gram of L-arginine per 3 capsule dose incorporated into a neurotransmitter production support delivery system termed N.P.S.™ . Loading dose was 3 capsules per day, 2 times per day, for 3 days. Arginine Derived Nitric Oxide (ADNO) levels were tested via skin surface temperature changes and Siemens’ Nitric Oxide breathalyzer/analyzer.
HemOxideTM Ingredients: L-Arginine, Choline Bitartrate, Cocoa, Organic Sugar, Vitamin C, Thiamin, Riboflavin, Niacin, Calcium Pantothenate, Pyridoxine, L-Histidine, L-Glutamic Acid, N-Acetyl-L Cysteine, Horse Chestnut Seed (20%).
HemOxideTM produces significantly more nitric oxide for substantially longer than
L-arginine alone.

Subjects receiving placebo had no spike in Nitric Oxide (NO) production from baseline. Subjects receiving l-arginine alone experienced an average 8% increase in NO production within the first 10 minutes and then gradually declined to less than 2% at the 15 minute point. Subjects receiving Hemoxide experienced increased NO levels for 1-4 hours reaching the same initial 10 minute 8% increase as L-arginine subjects, but then reaching an average 33% increase in NO production over baseline at the 15 minute point. Increased NO production in the Hemoxide subjects did not drop below 20% until the 60 minute point, gradually declining to 8% over baseline (where L-arginine subjects peaked) at the 105 minute point.
Conclusion
Where single nutrient supplementation without right delivery method is concerned, this study joins many others in supporting the specific notion that single nutrient oral supplementation does not work. However, when formulated with synergistic cofactors or delivery systems (similar to pharmaceuticals), this study confirms supplements can and do work. This study supports emulating nature in formulation, especially green leafy vegetables, as these foods produce NO, the body’s key endogenous nutrient delivery system (1). This study supports the taking of single nutrients and antioxidants with NO yielding foods (to include greens powders). Lastly this study encourages an evolution in single nutrient study protocols and proposes efforts to discover hidden cofactors to single nutrients with great therapeutic potential (as was done in this study when Choline Bitartrate was discovered a hidden co-factor to L-arginine in NO).
References
- Lundberg, J., et al. 2006. Cardioprotective effects of vegetables: Is nitrate the answer? Nitric Oxide Biology and Chemistry 15 (4): 359-362.
Formulators
Our company has worked within the Clinical Medical Foods environment since the mid 1990s and is gaining momentum for large Animal Health and Human OTC products. The Principal intellectual Property of the company is N.P.S.™ a ‘platform technology’ that allows amino acids to operate at doses 2%-5% of what was previously thought possible. We have translated the NO, acetylcholine, dopamine, and serotonin NT delivery systems, in addition to organ specific delivery systems.