Clinical Studies Injury to human skin
Human skin is know to produce the high amounts of Nitric Oxide and skin cells also produce hydrogen peroxide. This causes a problem in that high levels of peroxynitrite are also produced. Burned, damaged or infected skin produces even higher levels of peroxynitrite, which damages non damaged cells and immune cells and drugs needed to treat the damaged skin. An example of this is the use of Acyclovir on cold sore lesions. Acyclovir is effective when taken orally or intervenously, but topically its effect has been minimal. Infections with herpes simplex virus I (HSV-1) induces a persistent nuclear translocation of NF-kappa B, which is dramatically enhanced by peroxynitrite. The activation of NF-kappa B promotes efficient replication by HSV. In epithelial cells HSV-1 induces NF-kappa B causing persistent activation of NF-kappa B, which is a critical regulator of HSV-1 replication in skin. In AIDs patients, HIV-1 also triggers and activates NF-kappa B and AIDS patients have elevated levels of peroxynitrite, which contributes to the etiology of AIDS related dementia, persistent immunosuppression and Kaposis sarcoma. Peroxynitrite have also been shown to be very destructive to CD4 and CD8 cells. We have discovered that alpha-keto acids can decrease the levels and production of peroxynitrite, while protecting Nitric Oxide which can enhance the viral kill rate, while protecting drugs like Acyclovir.
This experiment was designed to show that medicines used to treat infections and cancer can be destroyed by the endogenous production of peroxynitrite, and that their by-products will cause the over production of peroxynitrite which will cause the over expression of NF-kappa B, thus delay the healing process. Various antibacterial, antifungals, anticancer and antiviral drugs were placed into solutions containing peroxynitrite. When the peroxynitrite treated drugs were placed on dermabraided skin they caused irritations do to the toxic breakdown products that were produced. They also delayed healing when compared to peroxynitrite treated drugs that were tested with the addition of alpha-keto acids.
When peroxynitrite is tested alone on derabriaded skin it activates inflammation and delays healing. Peroxynitrite drug by products are detoxified by alpha-keto acids and do not increase inflammation. Healing was at least 40% better with the keto acids.
In the second experiment , various wound sites were made on a patients arm with strip tape which produces a shallow derm abrasion. Derm abrasion will activate the production of Nitric Oxide and hydrogen peroxide and generate peroxynitrite which activates NF-kappa B which will produce inflammatory agents that will increase erythema, swelling, and delay healing. The various drugs were tested by them selves and in combination with the five keto acids and compared Time to healing was determined visually when redness and reepithelization occurred.
What we discovered was that these alpha-keto acids, somehow through an new mechanism, mitigated the damage from drugs and the toxic metabolites of these drugs that appeared to have activated NF-kappa B through peroxynitrite.
Laser skin resurfacing has become a very popular and prevalent cosmetic procedure to rejuvenate photoaged skin. Candidates for this procedure generally have a greater than average amount of photoaging and likely have depleted antioxidants. In addition, the greatest complaint surrounding these procedures is the long period of wound-healing and prolonged erythema pain, swelling, and crusting.
The purpose of the study was to compare the effects of 5 alpha-keto acids for their effects on the rate of cutaneous healing, and the ability of alpha-keto acids to reduce inflammation, specifically peroxynitrite at the test sites. All 5 alpha-keto acid wound-healing formulations were effective in accelerating wound healing in the model and all reduced redness. Other antioxidants, such as vitamin C, vitamin E do not reduce redness and appear to be ineffective against peroxynitrite.
Inhibition of Irritation and Cytotoxicity of Therapeutic Agents
All seven of the enumerated keto acids were placed into a commercially available triple antibiotic ointment. The triple antibiotic ointment without the keto acids produced an irritation of the skin from the antibiotics. The formulations with the keto acids did not. They inhibited the over production of peroxynitrite which causes the over expression of NF-kappa B, which reduced healing times considerably. Time in which healing took place on the skin was enhanced by three days with the keto acid formulations.
The same formula was used to treat dry winter skin, where it worked to prevent winter itch, cracking and pain. Hydrocortisone was also formulated with the keto acids to also treat dry skin. This formula reduced redness and pain.
Cold Sore Formulation
A commercial cold sore formula was purchased and the seven enumerated keto acids were placed into it to treat cold sores, both as a combination and singly as well. The commercial formulation by itself was utilized as a control. The normal cold sore formulas with phenol, an antiviral agent, did not work very well. However, when keto acids are placed in the cold sore formulation either singly or in combination with other keto acids , they heal the cold sore at a much faster rate when tested on a cold sore sufferer. The keto acids reduced lesion size and duration by 40% when compared to the control formula without alpha-keto acids.