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Male Sexual Function

OxyStim Research & Bibliography

A Significant Health Issue for Men

Man holding woman

Sexual activity is an important indicator of the overall health and well-being of men. A healthy and satisfying sex life is closely associated with a healthy lifestyle. Male sexual performance is mainly evaluated by erectile function.

Sexual function is physiologically correlated with age and also with one’s psychological and emotional state. Approximately 50% of men between 40 and 75 years old could be concerned by a decrease of erectile function (NIH Consensus Conference, 2012, 2013).

A decrease of sexual performance could lead to important psychological consequences such as: anxiety, mood and lack of self-esteem, contributing to a vicious circle.

Sexual Performance Factors

Men’s sexual function is based on erection ability to be spontaneous, firm and lasting all intercourse.

The erection mechanism is the combination of three functions. First, the brain is involved by controlling all male senses (sight, hearing, smell touch and thought).

Then, physical or psychogenic stimulation induces a neurochemical message, carried by the nerves to the penis artery.

Nitric oxide (NO) production is then stimulated in endothelial cells which leads to blood flow increase within the penis artery. At this stage, the smooth muscle is relaxed, the sinusoid cavities are swelled with blood and the vein is flattened which limits the blood exit. The maximum erection rigidity is now achieved.

The sexual function of healthy men, or the erection ability, closely depends on two factors. Psychological state, such as emotional tiredness, anxiety or stress, can impact sexual performance.

Nitric Oxide Graphic Stroke Chart

Organic factors such as NO bioavailability or smooth muscle cell relaxation have effects on blood flow. A healthy blood flow promotes erectile function.

About 80% of men with a decrease of sexual performance report an organic cause, especially vasculogenic (circulation) factor, age-related NO deprivation/ reduced blood flow, even if psychogenic factors (depression, anxiety…) are often present.

Decrease of blood flow has been associated with low erectile function. A decrease of erectile function is considered as the early stage of vascular decline associated with age. Therefore, maintenance of healthy blood flow represents a long term interesting challenge to preserve erectile function and sexual performance.

Factors Implications in the erection mechanism
Age + 60 years old Vascular health decrease /Blood flow decrease
Psychological State Emotional tiredness, Anxiety, Stress Loss of libido, Overinhibition
Organic Factors Inadequate nitric oxide release Lack of NO bioavailability /Blood flow decrease
Impaired smooth muscle Lack of relaxation/ Blood flow decrease
Damage to the nerves Neurochemical message transmission interrupted
Impaired blood pressure Blood flow decrease
Alcohol Slowing of nerve communication
Tobacco Blood flow decrease
Table 1: Causes having effect on erection mechanism

NO is likely the main mediator involved in penile erection mechanism and the most important target to improve organic factors implicated in erectile function.

Erection Mechanism at the Macroscopic Level

Penile erection (PE) is the result of a complex physiologic process involving a coordinated interaction between the blood vessels and the nerves.

Erectile Tissue

In the flaccid state, arterial vessels contained in the corpus cavernosum are constricted when cavernosal smooth muscles are contracted, allowing only a weak blood flow (Fig. 1).

Sexual stimulation, either psychogenic or reflexogenic, triggers neuronal NO release which initiates penile tumescence (normal engorgement with blood of the erectile tissues) and neuronal acetylcholine (Ach) release which eases tumescence promotion (Burnett, 2004).

ACh activates endothelial nitric oxide synthase (eNOS) transforming arginine precursor into endothelial nitric oxide (eNO). After several biochemical reactions (Fig. 2), the relaxation of cavernosal smooth muscles leads to an increase of blood flow in the corpus cavernosum. Burnett, 1997)


NO dependent blood flow: the most targeted mechanism of action

Figure 2 Smooth Muscle RelaxationFigure 2: Molecular mechanism of penile smooth muscle relaxation in corpus cavernosum

Decrease of sexual performance is mainly described as coming from a lack of NO bioavailability (Burnett, 2006; Burnett, 1997). Different approaches exist but the great majority are using the NO dependent blood flow modulation pathway.

Most of the products supporting erectile function and male sexual performance are targeting NO dependent blood flow mechanism by modulating biochemicals implicated at different steps (Muniz JJ, 2013).

A part of these approaches are focusing on direct NO replenishment in the corpus cavernosum (Soni SD, 2013) or on endothelial NO synthase activation (Subramoniam A, 2013): this is the mechanism of action of OxyStim.

In addition to its important role on smooth muscles relaxation previously described, eNO source from corpus cavernosum cells enhances the Vascular Endothelial Growth Factor (VEGF) synthesis (Komori 2008). VEGF is recognized to participate to the erectile function improvement by inhibiting endothelial apoptosis (processes leading to the death of cells (Rogers RS, 2003; Liu G, 2013).

Furthermore, administration of pure exogenous arginine, the eNOS substrate, did not demonstrate significant efficiency to improve erectile function (Klotz T, 1999), meaning that targeting NO precursor is not adapted. It should be more relevant to act on the enzyme in charge of eNO synthesis (eNOS) to obtain higher quantity of bioavailable NO. That's what OxyStim's active achieves and why arginine-based NO enhancers have poor efficacy.

NO synthase enzyme, and especially eNOS from endothelial cells in the corpus carvernosum, is a remarkable target with a high potential regarding male sexual performance. Studies indicate that OxyStim's EnoSTIM lives up to that potential by increasing blood flow by up to 50% to penile erectile tissue.

OxyStim's EnoSTIM activated eNOS by 43%, inducing a 24% increase of bioavailable NO. This activity resulted in a 50% increase in vasodilation or blood flow to the bodys' cells, tissues, and organs including penile erectile tissue.

OxyStim: Formulation of proprietary grape and apple skin polyphenols and saffron

To obtain an optimized action on NO secretion, OxyStim's research licensor, Nexira, developed a specific combination of flavonoids extracted proprietarily from grape skin and polyphenols from apple skin. Saffron, traditionally used in Iran for its effects on sexual and libido applications, was combined in Nexira's formulation, to achieve synergistic activities.

In vitro - HUVEC cells trials:

Nexira's research demonstrated that eNOS activation is permitted through phosphorylation of serine 1117 (mechanism of regulating protein function and transmitting signals throughout cells). Among several formulations, Nexira's proprietary acute polyphenol formulation, was selected as it reached its highest results on serine 1177 phosphorylation during an in vitro trial on endothelial cells (HUVEC).

EnoSTIM showed the highest potential on eNOS activation

The combination of the proprietary acute polyphenols and saffron showed an activity on eNOS with complementary mechanisms, supporting their unique synergy: acute polyphenols act on enzyme activation (through Serine 1177 phosphorylation) while saffron increases mRNA expression(messenger RNA molecules convey genetic information from DNA to the ribosome, where they specify the amino acid sequence of the protein products of gene expression) leading to an augmentation of this enzyme amount (Fig. 3).

Figure 3: Synergistic effects of ingredients composing EnoSTIM (acute polyphenols and saffron) Figure 5 OxyStim




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