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I forgot to address this question.
Alot of women on skin forums tend to use vitamin C topically and report having positive effects on skin firmness and elasticity.
This study shows that even 5% Vit.C demonstrates a clinically significant improvement in photodamaged skin. I'm a bit disappointed they didnt talk much about the vehicle...
Luckily this study gives us a starting point to achieve an optimal way of delivering Vit.C topically:
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Vit. C is available in the market as a variety of creams, serum and transdermal patches. Of these, only the serum contains active Vit. C in an almost colorless form. It is unstable and, on exposure to light, gets oxidized to Dehydro Ascorbic Acid (DHAA), which imparts a yellow color. The stability of Vit. C is controlled by maintaining a pH of less than 3.5. At this pH, the ionic charge on the molecule is removed and it is transported well across the stratum corneum.[3,5,9]
From a clinical point of view, it is important to note that the efficacy of the Vit. C serum is proportional to the concentration, but only up to 20%.[3] The half-life in the skin after achieving maximum concentration is 4 days. A persistent reservoir of Vit. C is important for adequate photoprotection, and can be achieved by regular 8-hourly applications.[1,5] As UV light lowers tissue Vit. C levels, topical Vit. C is best used after exposure to UV light and not prior.[1–3] A combination of tyrosine, zinc and Vit. C has been shown to increase the bioavailability of Vit. C 20-times vis-à-vis using just Vit. C.[2]
Note: You probably dont want to just mix these up randomly. I'll find a formulation with the optimal concentrations of each and if this is actually true
A variety of creams with Vit. C derivatives are available in the market. As a dermatologist, it is important to know that not all preparations are physiologically effective. Some are not delivered into the dermis in an adequate quantity, while others do not chemically convert to the biologically active form of Vit. C in the skin.[1,2,4]
Note: This is the most crucial part. I'll do more research on this.
Magnesium ascorbyl phosphate (MAP) is the most stable and preferred ascorbyl ester. This lipophilic molecule is easily absorbed into the skin, and the rate-limiting step for absorption is its release from the vehicle, and not the rate of diffusion across the stratum corneum as one might suppose. MAP has a hydrating effect on the skin and decreases transepidermal water loss. It is also a free radical scavenger that is photoprotective and increases collagen production under laboratory test conditions.[1,3] Other useful stable esterified derivatives are:
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MAP might be a better alternative to Vit C seeing as its more stable and readily used by skin cells.
Also:
Maybe ferulic acid can increase efficiency of MAP?
This is could be helpful in reducing androgen mediated/ROS induced oxidative damage . I've got more questions than answers so I'll look into this a bit more.
Found a lead:
A conserved family of prolyl-4-hydroxylases that modify HIF.
HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.
Those studies are the references that describe the pro-HIF-1alpha effects of stemoxydine. HIF-1 stimulates VEGF, and an increase in DPC blood supply actually increases hair diameter and growth rate (check first post for more info). I'm going to do some more reading when I have time, this might be interesting.
Topical spiro is a tricky one. There are a handful of people that seen improvements and others that claim it goes systemic (leading to gyno). Theoretically, inhibition of systemic AR results in the HPTA pumping out more testosterone to satisfy negative feedback loop, so you shouldnt experience serious gyno. There is only one study that tested spiro for systemic absorption and they only measured hormone levels over 72hrs, which wouldnt be greatly affected anyway since its an AR blocker. They also saw no increase in the metabolite which is sketchy imo. Plus it was a while ago. http://www.ncbi.nlm.nih.gov/pubmed/3411088
This hamster study: http://www.ncbi.nlm.nih.gov/pubmed/7608379
shows that topical spiro blunted exogenous testosterone induced sebaceous gland growth, which means its doing something.
Its also been used to treat female pattern hairloss with vary degrees of success, but female scalp is not exactly the same as male scalp physiologically (gender dependant receptor and protein expression variability). Then theres the side effects - although typical low doses shouldnt be a problem if it indeed doesnt go systemic.
I wanted to try spiro and thought it would be an ideal candidate to block AR. Flutamide has better physiological responses but its got considerable hepatotoxicity risks. Bicalutamide seems like a better canditate since its got a ridiuculous half life, but theres still not enough information on topical administration and systemic effects, I suspect it'll most probably go systemic using standard skin penetration vehicles. Personally? I wouldnt advocate spiro with insufficient evidence on its efficacy.
Alot of women on skin forums tend to use vitamin C topically and report having positive effects on skin firmness and elasticity.
This study shows that even 5% Vit.C demonstrates a clinically significant improvement in photodamaged skin. I'm a bit disappointed they didnt talk much about the vehicle...
Topical ascorbic acid on photoaged skin. Clinical, topographical and ultrastructural evaluation: double-blind study vs. placebo.
Vitamin C is known for its antioxidant potential and activity in the collagen biosynthetic pathway. Photoprotective properties of topically applied vitamin C have also been demonstrated, placing this molecule as a potential candidate for use in the prevention and treatment of skin ageing. A topically applied cream containing 5% vitamin C and its excipient were tested on healthy female volunteers presenting with photoaged skin on their low-neck and arms in view to evaluate efficacy and safety of such treatment. A double-blind, randomized trial was performed over a 6-month period, comparing the action of the vitamin C cream vs. excipient on photoaged skin. Clinical assessments included evaluation at the beginning and after 3 and 6 months of daily treatment. They were performed by the investigator and compared with the volunteer self assessment. Skin relief parameters were determined on silicone rubber replicas performed at the same time-points. Cutaneous biopsies were obtained at the end of the trial and investigated using immunohistochemistry and electron microscopy. Clinical examination by a dermatologist as well as self-assessment by the volunteers disclosed a significant improvement, in terms of the 'global score', on the vitamin C-treated side compared with the control. A highly significant increase in the density of skin microrelief and a decrease of the deep furrows were demonstrated. Ultrastructural evidence of the elastic tissue repair was also obtained and well corroborated the favorable results of the clinical and skin surface examinations. Topical application of 5% vitamin C cream was an effective and well-tolerated treatment. It led to a clinically apparent improvement of the photodamaged skin and induced modifications of skin relief and ultrastructure, suggesting a positive influence of topical vitamin C on parameters characteristic for sun-induced skin ageing.
Vitamin C is known for its antioxidant potential and activity in the collagen biosynthetic pathway. Photoprotective properties of topically applied vitamin C have also been demonstrated, placing this molecule as a potential candidate for use in the prevention and treatment of skin ageing. A topically applied cream containing 5% vitamin C and its excipient were tested on healthy female volunteers presenting with photoaged skin on their low-neck and arms in view to evaluate efficacy and safety of such treatment. A double-blind, randomized trial was performed over a 6-month period, comparing the action of the vitamin C cream vs. excipient on photoaged skin. Clinical assessments included evaluation at the beginning and after 3 and 6 months of daily treatment. They were performed by the investigator and compared with the volunteer self assessment. Skin relief parameters were determined on silicone rubber replicas performed at the same time-points. Cutaneous biopsies were obtained at the end of the trial and investigated using immunohistochemistry and electron microscopy. Clinical examination by a dermatologist as well as self-assessment by the volunteers disclosed a significant improvement, in terms of the 'global score', on the vitamin C-treated side compared with the control. A highly significant increase in the density of skin microrelief and a decrease of the deep furrows were demonstrated. Ultrastructural evidence of the elastic tissue repair was also obtained and well corroborated the favorable results of the clinical and skin surface examinations. Topical application of 5% vitamin C cream was an effective and well-tolerated treatment. It led to a clinically apparent improvement of the photodamaged skin and induced modifications of skin relief and ultrastructure, suggesting a positive influence of topical vitamin C on parameters characteristic for sun-induced skin ageing.
--------------------------------
Vit. C is available in the market as a variety of creams, serum and transdermal patches. Of these, only the serum contains active Vit. C in an almost colorless form. It is unstable and, on exposure to light, gets oxidized to Dehydro Ascorbic Acid (DHAA), which imparts a yellow color. The stability of Vit. C is controlled by maintaining a pH of less than 3.5. At this pH, the ionic charge on the molecule is removed and it is transported well across the stratum corneum.[3,5,9]
From a clinical point of view, it is important to note that the efficacy of the Vit. C serum is proportional to the concentration, but only up to 20%.[3] The half-life in the skin after achieving maximum concentration is 4 days. A persistent reservoir of Vit. C is important for adequate photoprotection, and can be achieved by regular 8-hourly applications.[1,5] As UV light lowers tissue Vit. C levels, topical Vit. C is best used after exposure to UV light and not prior.[1–3] A combination of tyrosine, zinc and Vit. C has been shown to increase the bioavailability of Vit. C 20-times vis-à-vis using just Vit. C.[2]
Note: You probably dont want to just mix these up randomly. I'll find a formulation with the optimal concentrations of each and if this is actually true
A variety of creams with Vit. C derivatives are available in the market. As a dermatologist, it is important to know that not all preparations are physiologically effective. Some are not delivered into the dermis in an adequate quantity, while others do not chemically convert to the biologically active form of Vit. C in the skin.[1,2,4]
Note: This is the most crucial part. I'll do more research on this.
Magnesium ascorbyl phosphate (MAP) is the most stable and preferred ascorbyl ester. This lipophilic molecule is easily absorbed into the skin, and the rate-limiting step for absorption is its release from the vehicle, and not the rate of diffusion across the stratum corneum as one might suppose. MAP has a hydrating effect on the skin and decreases transepidermal water loss. It is also a free radical scavenger that is photoprotective and increases collagen production under laboratory test conditions.[1,3] Other useful stable esterified derivatives are:
------------------------------
MAP might be a better alternative to Vit C seeing as its more stable and readily used by skin cells.
Also:
A combination of 0.5% ferulic acid (a potent antioxidant of plant origin) with 15% Vit. C and 1% Vit. E can increase the efficacy of Vit. C eight-fold.[3] It was noted that this triple combination was very useful for the reduction of acute and chronic photodamage, and could be used for prevention of skin cancer in the future.
This is could be helpful in reducing androgen mediated/ROS induced oxidative damage . I've got more questions than answers so I'll look into this a bit more.
Found a lead:
Stemoxydine (active ingredient in Neogenic) = diethyl pyridine-2,4-dicarboxylate
A bit more info on the molecule...
A bit more info on the molecule...
2,4-Diethylpyridine dicarboxylate
The pro-angiogenic factor HIF-1α is targeted for destruction in normoxic environments by the hydroxylation of a specific proline residue, P564, by the oxygen-sensing enzyme HIF-α prolyl hydroxylase (HIF-PH).1 2,4-DPD is a cell permeable, competitive inhibitor of HIF-PH. 2,4-DPD inhibits the hydroxylation of P564 by acting as a competitive inhibitor of the HIF-PH cofactor α-keto glutarate, with effective concentrations in the low µM range.2 2,4-DPD is therefore expected to act as a pro-angiogenic compound, via the HIF-1α system.3,4
The pro-angiogenic factor HIF-1α is targeted for destruction in normoxic environments by the hydroxylation of a specific proline residue, P564, by the oxygen-sensing enzyme HIF-α prolyl hydroxylase (HIF-PH).1 2,4-DPD is a cell permeable, competitive inhibitor of HIF-PH. 2,4-DPD inhibits the hydroxylation of P564 by acting as a competitive inhibitor of the HIF-PH cofactor α-keto glutarate, with effective concentrations in the low µM range.2 2,4-DPD is therefore expected to act as a pro-angiogenic compound, via the HIF-1α system.3,4
HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.
Those studies are the references that describe the pro-HIF-1alpha effects of stemoxydine. HIF-1 stimulates VEGF, and an increase in DPC blood supply actually increases hair diameter and growth rate (check first post for more info). I'm going to do some more reading when I have time, this might be interesting.
Topical spiro is a tricky one. There are a handful of people that seen improvements and others that claim it goes systemic (leading to gyno). Theoretically, inhibition of systemic AR results in the HPTA pumping out more testosterone to satisfy negative feedback loop, so you shouldnt experience serious gyno. There is only one study that tested spiro for systemic absorption and they only measured hormone levels over 72hrs, which wouldnt be greatly affected anyway since its an AR blocker. They also saw no increase in the metabolite which is sketchy imo. Plus it was a while ago. http://www.ncbi.nlm.nih.gov/pubmed/3411088
This hamster study: http://www.ncbi.nlm.nih.gov/pubmed/7608379
shows that topical spiro blunted exogenous testosterone induced sebaceous gland growth, which means its doing something.
Its also been used to treat female pattern hairloss with vary degrees of success, but female scalp is not exactly the same as male scalp physiologically (gender dependant receptor and protein expression variability). Then theres the side effects - although typical low doses shouldnt be a problem if it indeed doesnt go systemic.
I wanted to try spiro and thought it would be an ideal candidate to block AR. Flutamide has better physiological responses but its got considerable hepatotoxicity risks. Bicalutamide seems like a better canditate since its got a ridiuculous half life, but theres still not enough information on topical administration and systemic effects, I suspect it'll most probably go systemic using standard skin penetration vehicles. Personally? I wouldnt advocate spiro with insufficient evidence on its efficacy.
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