27 replies to this topic

[Phoenicis]

Out of interest, I'm wondering if there are any agents of use for hair loss, I'm young (24) and hoping to avoid losing any more than have to. Perhaps acting preemptively now while the loss is less severe is the best plan of action. I am already on curcumin and resveratrol, they are mentioned in some research anyone know if any of the others bellow might work?

 

The reason why I am interested in epigenetics - I have seen some very encouraging results from using curcumin and resveratrol as epigenetic agents to treat psoriais. A non-inflammatory vegan diet (low on arachidonic acid, saturated fat, gluten etc) has helped alot too and probably helped reduce the threshold of inflammation to be overcome by the curcumin and resveratrol. I also believe that boosting butyrate production by gut microbes may be helping for the epigentic changes to work. I try to get the boost this by consuming lots of fruit and vigis while also taking resistant potato starch and FOS. There has also been a huge improvement in mood, probably related to more butyrate. Another factor at play could also be less uric acid (elevated in psoriais patients) as a result of less purines from meat. Anyways, I digress...

 

I'm not sure if curcumin and resveratrol have helped with hair loss. The only thing thats helped me so far is nizoral.

• Hair Foundation Article - Genes, Hair Growth and Hair Loss
• hairfoundation.org/hair-library
• Pharmaceutical composition comprising curcumin and resveratrol and uses thereof in medical field (not trying to copy or use this!! merely posted to prove that there has been interest in this area)
• S Coccoloni, D Turini - US Patent App. 12/067,291, 2006 - Google Patents

• Growth suppression of hamster flank organs by topical application of catechins, alizarin, curcumin, and myristoleic acid
• S Liao, J Lin, MT Dang, H Zhang, YH Kao… - Archives of …, 2001 - Springer

• The hair growth promoting effect of< i> Asiasari radix</i> extract and its molecular regulation
• SS Rho, SJ Park, SL Hwang, MH Lee, CD Kim… - Journal of …, 2005 - Elsevier

• The hair growth promoting effect of< i> Sophora flavescens</i> extract and its molecular regulation
• SS Roh, CD Kim, MH Lee, SL Hwang, MJ Rang… - Journal of …, 2002 - Elsevier

• Hair growth promoting effect of< i> Zizyphus jujuba</i> essential oil
• JI Yoon, SM Al-Reza, SC Kang - Food and chemical toxicology, 2010 - Elsevier

• Antiangiogenic agents: studies on fumagillin and curcumin analogs
• MS Furness, TP Robinson, T Ehlers… - Current …, 2005 - ingentaconnect.com

• Inhibition of hair growth (not trying to copy or use this!! merely posted to illustrate what other uses curcumin comes to)
• S Coccoloni, D Turini - US Patent App. 12/067,291, 2006 - Google Patents
• GS Ahluwalia, D Shander, P Styczynski - US Patent 5,554,608, 1996 - Google Patents

 

 

Edited by Phoenicis, 13 April 2014 - 08:58 PM.

[Turnbuckle]

Take a look at this one--http://www.google.co...9114089A2?cl=en

[Phoenicis]

http://www.hairloss-...aisesSHBG.html:

 

"GREEN TEA RAISES SHBG-HAIRLOSS/MPB BENEFIT
 

SHBG Levels and Hair Loss

There is a clinically established inverse relationship between sex hormone binding globulin (SHBG) and androgenetic alopecia (AGA). Studies have shown that those with AGA have lower circulating levels of SHBG compared to the non-balding controls.

There are several drugs (like oral antiandrogens) that elevate SHBG levels but have a host of side effects that limit their usage on a continuous basis in men.

There are also, however, two health enhancing compounds that elevate SHBG levels while offering additional health benefits and are side effect free. Green Tea Extract elevates SHBG while having the added benefit of reducing estrogen levels, which via an SHBG binding route can upregulate androgen activity. Soy isoflavones have also been shown in several studies to elevate SHBG levels and to be mildly anti-estrogenic.

In addition to a significantly lower incidents of most types of cancer, including prostate cancer and breast cancer, the oriental population whose traditional diet is abundant in soy isoflavones and green tea catechins have a drastically lower overall incidence of androgenetic alopecia and acne compared to the US.

Interestingly, those of Asian origin living in the US have an almost identical incidence of androgen mediated disorders (prostate cancer, BPH, hair loss) as the US general population.

[...]
Dietary isoflavones affect sex hormone-binding globulin levels in postmenopausal women.
Pino AM, Valladares LE, Palma MA, Mancilla AM, Yanez M, Albala C. Instituto De Nutricion y Tecnologia de Los Alimentos, Universidad de Chile, Santiago.

The studies presented in this report were designed to further investigate the causal association between phytoestrogen action and increase in sex hormone-binding globulin (SHBG) levels. Phytoestrogens include isoflavones that bind to estrogen receptors and therefore exert estrogenic action. This study included 20 postmenopausal women that ingested 30 g soy milk daily for 10 weeks. Plasma concentrations of isoflavones and SHBG were measured. Total isoflavones significantly increased from 0.014 +/- 0.01 micromol/L(baseline) to 0.53 +/- 0.19, micromol/L, and paired responses showed that some subjects clearly increased their SHBG levels. The percent change in SHBG showed a positive correlation with phytoestrogen concentration; all women who had circulating phytoestrogen levels above 0.6 micromol/L increased by at least 30% their SHBG values. Results suggest that phytoestrogens may significantly increase SHBG in subjects whose SHBG concentrations are in the low end of the concentration range.

Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone-binding globulin in premenopausal Japanese women.
Nagata C, Kabuto M, Shimizu H.
Department of Public Health, Gifu University School of Medicine, Japan. chisato@cc.gifu-u.ac.jp

Caffeine intake has been proposed to influence breast cancer risk. Its effect may be mediated by hormonal changes. The relationships between caffeine-containing beverages (coffee, green tea, black tea, oolong tea, and cola) and serum concentrations of estradiol and sex hormone-binding globulin were evaluated in 50 premenopausal Japanese women. Intakes of caffeine and caffeine-containing beverages were assessed by a semiquantitative food-frequency questionnaire. Blood samples were obtained from each woman on Days 11 and 22 of her menstrual cycle. High intakes of caffeinated coffee, green tea, and total caffeine were commonly correlated with increasing sex hormone-binding globulin on Days 11 and 22 of the cycle after controlling for potential confounders [Spearman correlation coefficients ® ranged from 0.23 to 0.31]. Green tea but not caffeinated coffee intake was inversely correlated with estradiol on Day 11 of the cycle (r = -0.32, p = 0.04). Although the effect of caffeine cannot be distinguished from effects of coffee and green tea, consumption of caffeine-containing beverages appeared to favorably alter hormone levels associated with the risk of developing breast cancer."

-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

 

Human hair growth enhancement in vitro by green tea epigallocatechin-3-gallate (EGCG)

Abstract

"Green tea is a popular worldwide beverage, and its potential beneficial effects such as anti-cancer and anti-oxidant properties are believed to be mediated by epigallocatechin-3-gallate (EGCG), a major constituent of polyphenols. Recently, it was reported that EGCG might be useful in the prevention or treatment of androgenetic alopecia by selectively inhibiting 5α-reductase activity. However, no report has been issued to date on the effect of EGCG on human hair growth.

This study was undertaken to measure the effect of EGCG on hair growth in vitro and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. EGCG promoted hair growth in hair follicles ex vivo culture and the proliferation of cultured DPCs. The growth stimulation of DPCs by EGCG in vitro may be mediated through the upregulations of phosphorylated Erk and Akt and by an increase in the ratio of Bcl-2/Bax ratio. Similar results were also obtained in in vivo dermal papillae of human scalps. Thus, we suggest that EGCG stimulates human hair growth through these dual proliferative and anti-apoptotic effects on DPCs."

 

The effects of tea polyphenolic compounds on hair loss among rodents.

Abstract

"The objective of this study was to examine the effects of polyphenolic compounds, present in noncommercially available green tea, on hair loss among rodentts. In an experimental study, we randomly assigned 60female Balb/black mice, which had developed spontaneous hair loss on the head, neck and dorsal areas into two equal groups; A (experimental) and B (control). Group A received 50% fraction of polyphenol extract from dehydrated green tea in their drinking water for six months. Group B received regular drinking water. Both groups were fed regular rodent diets (Purina Rodent Chow 5001) and housed individually in polycarbonate cages. The results showed that 33% of the mice in experimental Group A, who received polyphenol extract in their drinking water, had significant hair regrowth during six months of treatment (p = 0.014). No hair growth was observed among mice in the control group, which received regular water."

 

Cisplatin-Induced Hair Cell Death Requires STAT1 and Is Attenuated by Epigallocatechin Gallate:

Abstract

Cisplatin is a chemotherapy drug that frequently causes auditory impairment due to the death of mechanosensory hair cells. Cisplatin ototoxicity may result from oxidative stress, DNA damage, and inflammatory cytokines. The transcription factor STAT1, an important mediator of cell death, can regulate all of these processes in other cell types. We used cultured utricles from mature Swiss Webster mice to investigate the role of STAT1 in cisplatin-induced hair cell death. We show that STAT1 phosphorylation is an early event in both hair cells and support cells after exposure of utricles to cisplatin. STAT1 phosphorylation peaked after 4 h of cisplatin exposure and returned to control levels by 8 h of exposure. The STAT1 inhibitor epigallocatechin gallate (EGCG) attenuated STAT1 phosphorylation in cisplatin-treated utricles and resulted in concentration-dependent increases in hair cell survival at 24 h postexposure. Furthermore, we show that utricular hair cells from STAT1-deficient mice are resistant to cisplatin toxicity. EGCG failed to provide additional protection from cisplatin in STAT1-deficient mice, further supporting the hypothesis that the protective effects of EGCG are due to its inhibition of STAT1. Treatment with IFN-γ, which also causes STAT1 activation, also induced hair cell death in wild-type but not STAT1-deficient mice. These results show that STAT1 is required for maximal cisplatin-induced hair cell death in the mouse utricle and suggest that treatment with EGCG may be a useful strategy for prevention of cisplatin ototoxicity.

 

Modulation of Endocrine Systems and Food Intake by Green Tea Epigallocatechin Gallate

 

Abstract

"Green tea polyphenols, especially the catechin, (−)-epigallocatechin gallate (EGCG), have been proposed as a cancer chemopreventative based on a variety of laboratory studies. For clear assessment of the possible physiological effects of green tea consumption, we injected pure green tea catechins ip into rats and studied their acute effects on endocrine systems. We found that EGCG, but not related catechins, significantly reduced food intake; body weight; blood levels of testosterone, estradiol, leptin, insulin, insulin-like growth factor I, LH, glucose, cholesterol, and triglyceride; as well as growth of the prostate, uterus, and ovary. Similar effects were observed in lean and obese male Zucker rats, suggesting that the effect of EGCG was independent of an intact leptin receptor. EGCG may interact specifically with a component of a leptin-independent appetite control pathway. Endocrine changes induced by parenteral administration of EGCG may relate to the observed growth inhibition and regression of human prostate and breast tumors in athymic mice treated with EGCG as well as play a role in the mechanism by which EGCG inhibits cancer initiation and promotion in various animal models of cancer."

 

Potentially worrisome, I wonder at what dose green tea extracts can cause this? -

 

Acute hepatitis after treatment for hair loss with oral green tea extracts (Camellia Sinensis).

 

"Nutritional additives based on green tea have been claiming various beneficial health effects. However, several case reports on hepatotoxicity after the intake of green tea derivatives containing Camellia Sinensis have been published. We report a patient with an acute hepatitis after intake of an oral green tea derivative claiming protection against hair loss, showing a histological image compatible with drug induced hepatitis. Other important causes of hepatitis were excluded. After cessation of this nutritional additive there was a rapid and sustained recovery. We raise concern about the safety of nutritional additives with few proven beneficial effects and want to emphasize the importance of accurate and thorough history taking, with attention for over the counter drugs and herbal products."

 

Edited by Phoenicis, 13 April 2014 - 11:00 PM.

[Phoenicis]

Another reason to love indian gooseberries? I heard that it was used for hair treatment in India. Coincidentally I make my own capsules and only started taking them last week. Some other plants as well:

 

5α-reductase inhibition and hair growth promotion of some Thai plants traditionally used for hair treatment:

 

Abstract Ethnopharmacological relevance

Many Thai traditional herbs have been used for hundreds of years for hair treatment and nourishment, including hair loss. However, scientific evidence about their mechanisms of action has not yet been elucidated.

Aims of the study

The purpose of this research is to define the possible mechanisms involved in hair loss treatment of the selected plants by determining the 5α-reductase enzyme inhibition and hair growth promoting activities, and the relationship between these two activities.

Materials and methods

Seventeen Thai plants traditionally used for hair treatment were selected. The plants were dried, ground and extracted by maceration with ethyl alcohol. These extracts were further tested for 5α-reductase inhibition using enzymes from rat livers. Hair growth promoting activity was tested in C57BL/6 mice.

Results

Carthamus tinctorius L. was the most potent 5α-reductase inhibitor, with a finasteride equivalent 5α-reductase inhibitory activity (FEA) value of 24.30 ± 1.64 mg finasteride equivalent per 1 g crude extract. Phyllanthus emblica L. was the second most potent inhibitor, with FEA of 18.99 ± 0.40. Rhinacanthus nasutus (L.) Kurz. was the least potent 5α-reductase inhibitor (FEA 10.69 ± 0.96). Carthamus tinctorius also was the most potent hair growth promoter in C57BL/6 mice. There were strong relationships between 5α-reductase inhibitory activity and hair growth promoting activity (r = 0.719), and between 5α-reductase inhibitory activity and hair follicle count (r = 0.766).

Conclusions

Ethanolic extract of Carthamus tinctorius was the most potent 5α-reductase inhibitor and hair growth promoter. This discovery may lead to the development of new alternative medicines for hair loss prevention and treatment.

 

Rice Bran?

 

5α-Reductase type 1 inhibition of Oryza sativa bran extract prepared by supercritical carbon dioxide fluid

Abstract

The three crude extracts including Oryza sativa (bran) from supercritical carbon dioxide fluid (scCO₂) process which gave the highest unsaturated fatty acid contents and biological activities including the antioxidative, tyrosinase inhibition, stimulation index on human normal skin fibroblast were selected from ten edible plants to prepare the semi-purified fractions. Fraction No. 3 of the O. sativa bran crude extract gave the highest content of unsaturated fatty acids and 5α-reductase (type 1) inhibition activity (5AR). Its linoleic acid (LN) and total unsaturated fatty acid (TUC) contents were significantly positive and linear correlated to 5AR on DU-145 cell line (at r of 1.00, p < 0.01). Its total phenolic contents and all biological activities also showed positive correlations to 5AR with r > 0.9 (p < 0.05). This study has demonstrated the potential of fraction No. 3 fractionated from the O. sativa bran crude extract prepared by scCO₂ to be developed as anti-androgenic alopecia products.

 

Edited by Phoenicis, 13 April 2014 - 11:00 PM.

[mikey]

Another reason to love indian gooseberries? I heard that it was used for hair treatment in India. Coincidentally I make my own capsules and only started taking them last week. Some other plants as well:

 

5α-reductase inhibition and hair growth promotion of some Thai plants traditionally used for hair treatment:

 

Abstract Ethnopharmacological relevance

Many Thai traditional herbs have been used for hundreds of years for hair treatment and nourishment, including hair loss. However, scientific evidence about their mechanisms of action has not yet been elucidated.

Aims of the study

The purpose of this research is to define the possible mechanisms involved in hair loss treatment of the selected plants by determining the 5α-reductase enzyme inhibition and hair growth promoting activities, and the relationship between these two activities.

Materials and methods

Seventeen Thai plants traditionally used for hair treatment were selected. The plants were dried, ground and extracted by maceration with ethyl alcohol. These extracts were further tested for 5α-reductase inhibition using enzymes from rat livers. Hair growth promoting activity was tested in C57BL/6 mice.

Results

Carthamus tinctorius L. was the most potent 5α-reductase inhibitor, with a finasteride equivalent 5α-reductase inhibitory activity (FEA) value of 24.30 ± 1.64 mg finasteride equivalent per 1 g crude extract. Phyllanthus emblica L. was the second most potent inhibitor, with FEA of 18.99 ± 0.40. Rhinacanthus nasutus (L.) Kurz. was the least potent 5α-reductase inhibitor (FEA 10.69 ± 0.96). Carthamus tinctorius also was the most potent hair growth promoter in C57BL/6 mice. There were strong relationships between 5α-reductase inhibitory activity and hair growth promoting activity (r = 0.719), and between 5α-reductase inhibitory activity and hair follicle count (r = 0.766).

Conclusions

Ethanolic extract of Carthamus tinctorius was the most potent 5α-reductase inhibitor and hair growth promoter. This discovery may lead to the development of new alternative medicines for hair loss prevention and treatment.

 

Rice Bran?

 

5α-Reductase type 1 inhibition of Oryza sativa bran extract prepared by supercritical carbon dioxide fluid

Abstract

The three crude extracts including Oryza sativa (bran) from supercritical carbon dioxide fluid (scCO₂) process which gave the highest unsaturated fatty acid contents and biological activities including the antioxidative, tyrosinase inhibition, stimulation index on human normal skin fibroblast were selected from ten edible plants to prepare the semi-purified fractions. Fraction No. 3 of the O. sativa bran crude extract gave the highest content of unsaturated fatty acids and 5α-reductase (type 1) inhibition activity (5AR). Its linoleic acid (LN) and total unsaturated fatty acid (TUC) contents were significantly positive and linear correlated to 5AR on DU-145 cell line (at r of 1.00, p < 0.01). Its total phenolic contents and all biological activities also showed positive correlations to 5AR with r > 0.9 (p < 0.05). This study has demonstrated the potential of fraction No. 3 fractionated from the O. sativa bran crude extract prepared by scCO₂ to be developed as anti-androgenic alopecia products.

 

 

Your first post said, "The only thing thats helped me so far is nizoral."

 

Nizoral does penetrate (oily/waxy) sebum to inhibit inflammatory cytokines that cause hair follicle dormancy. I wrote the first hypothesis that this worked back in the 90's and a couple years later a study confirmed it and then several others over the next few years.

 

However, there are a number of other agents that combined yield greater benefits, as you can read at: http://www.michaelmooney.net/hair.html

 

I assume that there are several other agents that are effective. However, I basically quit researching the topic after experiencing some success.

 

However, one thing that isn't in that article that I believe has further improved my hair quality - C60 fullerene.

 

I've been taking 7 mg/day of C60oo since August, 2012, after reading Turnbuckle's experience with hair growth.

 

You can read about it on the forum on Longecity, titled c60-experiments-home/

[goodman]

how bout aromatherapy

[Phoenicis]

I'm going to try:

• EGCG for the upregulation of phosphorylated Erk and Akt and by an increase in the ratio of Bcl-2/Bax ratio and it's STAT1 inhibitor effect. It sould also result in more sex hormone binding globulin (SHBG) and less androgenetic alopecia (AGA),
• Indian gooseberry also decreases bcl-2 and increases BAX. I wonder if this plays a part in it's 5α-reductase inhibitor properties?
• resistant potato starch + FOS for increased butyrate, I'm not 100% sue if this will increase the efficacy of the above agents. Perhaps someone could chime in?

 

I'm going to empty some LEF decaffeinated green tea extract capsules and mix them with Indian gooseberry/amla power to produce a 50/50 mix. Then I'll make use my capsule machine to produce 700mg capsules containing 350mg green tea extract and 350mg Indian gooseberry.

 

I'm going with 2 x daily 350mg green tea extract because 700mg in one go can cause some liver issues in a 70kg male. I'll take this with food, twice a day since splitting 700mg like this seems not to cause as the same issues as 700mg once a day. The was a study in dogs showing that consumption of high doses of green tea extract was not toxic for the liver when taken with food. I'm not a doctor or a medical professional so dont rely on what I've said. Do see the quotes bellow from other threads.

 

I also wanted to share this review on the epigenetic effects of butyrate for those of you who are not familiar: http://www.clinicale...68-7083-4-4.pdf

 

Here is a study that shows why the toxicity will occur, unless this is some new mechanism than the other times around when we covered this issue:
http://clincancerres...t/full/9/9/3312

We conclude that p.o. administration of EGCG or Polyphenon E at a daily dose of 800 mg (based on the EGCG content) for 4 weeks is safe and well tolerated in healthy human subjects. Repeated green tea polyphenol administration at a high daily bolus dose (800 mg once daily) results in a >60% increase in the systemic exposure of EGCG, possibly because of inhibition of presystemic elimination of this catechin. Repeated administration of EGCG and Polyphenon E at a daily dose equivalent to the EGCG content in 16 Japanese-style cups of green tea for 4 weeks did not provide protection against UV-induced erythema.

also note:

The 400-mg twice daily regimen apparently did not result in tea catechin concentrations that would exert a significant inhibitory effect. The mechanism(s) responsible for the observed increase in the AUC of free EGCG after chronic treatment of EGCG/Polyphenon E at a high daily bolus dose remain(s) to be studied. Inhibitions in nonenzymatic degradation, intestinal flora metabolism, methylation, and/or intestinal efflux of EGCG are plausible contributing factors.

And here is the review in which the remarks from Chang are derived:
http://pubs.acs.org/.../tx7000515.html
Check out the mg/kg

Despite several human studies that showed no toxicity of tea polyphenol preparations and that the major adverse effects associated with consumption of high doses of tea preparations are due to gastrointestinal irritation, there have been a number of recent case reports of hepatotoxicity related to the consumption of high doses of tea-based dietary supplements (10-29 mg/kg/day po)

So the end result seems to be to take less than 800mg/day worth of EGCG. I would also consider splitting the dosage if taking 600mg worth or higher in a day.
This is what I take from it but I am not a doctor.

 

 

It's not the toxic metals. In vivo, the beneficial polyphenols in green tea are pro-oxidant redox cyclers:

Galati, Giuseppe, et al. "Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins." Free Radical Biology and Medicine 40.4 (2006): 570-580.
 

The cytotoxicities of these major tea phenolics toward isolated rat hepatocytes have been ranked and the mechanisms of cytotoxicity evaluated. The order of cytotoxic effectiveness found was epigallocatechin-3-gallate > propyl gallate > epicatechin-3-gallate > gallic acid, epigallocatechin > epicatechin. Using gallic acid as a model tea phenolic and comparing it with the tea catechins and gallic acid-derivative food supplements, the major cytotoxic mechanism found with hepatocytes was mitochondrial membrane potential collapse and ROS formation. Epigallocatechin-3-gallate was also the most effective at collapsing the mitochondrial membrane potential and inducing ROS formation. Liver injury was also observed in vivo when these tea phenolics were administered ip to mice, as plasma alanine aminotransferase levels were significantly increased. In contrast, GSH conjugation, methylation, metabolism by NAD(P)H:quinone oxidoreductase 1, and formation of an iron complex were important in detoxifying the gallic acid. In addition, for the first time, the GSH conjugates of gallic acid and epigallocatechin-3-gallate have been identified using mass spectrometry.

Small doses, good. Large doses, not so good.

Na, Hye-Kyung, and Young-Joon Surh. "Modulation of Nrf2-mediated antioxidant and detoxifying enzyme induction by the green tea polyphenol EGCG." Food and Chemical Toxicology 46.4 (2008): 1271-1278.
Mazzanti, Gabriela, et al. "Hepatotoxicity from green tea: a review of the literature and two unpublished cases." European journal of clinical pharmacology 65.4 (2009): 331-341.

Similar pluripotency against multiple oncogenic processes has been found with other extensively studied Nrf2 inducers like sulforaphane, curcumin, and CDDO-imidazole. EGCG doesn't seem particularly notable.

Wakabayashi, Nobunao, et al. "When Nrf2 talks, who's listening?."Antioxidants & redox signaling 13.11 (2010): 1649-1663.
Li, Wenge, et al. "Activation of Nrf2-antioxidant signaling attenuates NFκB-inflammatory response and elicits apoptosis." Biochemical pharmacology 76.11 (2008): 1485-1489.
Papp, Diána, et al. "The NRF2-related interactome and regulome contain multifunctional proteins and fine-tuned autoregulatory loops." FEBS letters586.13 (2012): 1795-1802.

The vast majority of naturally occuring Nrf2 inducers, like EGCG, have pro-oxidant activity, but there might be a better way, if one's planning chemoprevention with high dose supplements:

Martin-Cordero, Carmen, et al. "Pro-oxidant natural products as anticancer agents." Current Drug Targets 13.8 (2012): 1006-1028.
Satoh, Takumi, Scott R. McKercher, and Stuart A. Lipton. "Nrf2/ARE-mediated antioxidant actions of pro-electrophilic drugs." Free Radical Biology and Medicine 65 (2013):645-57

 

 

 

Edited by Phoenicis, 14 April 2014 - 02:18 PM.

[Phoenicis]

What's up Turnbuckle?

 

I need to try C60 some time, out of interest - what happens when you mix the oil with curcumin? Do the fullerenes interact with the curcumim in terms of bioavailability?

 

Take a look at this one--http://www.google.co...9114089A2?cl=en

 

Hi Mikey?

 

I had a look at your page and totally agree - I've been taking those supplements like iron to maje sure I'm not deficient. You think deficiency causes hair loss? I thought it was sex hormones. Did all of those things work for you or was it the c-60?

 

Your first post said, "The only thing thats helped me so far is nizoral."

 

Nizoral does penetrate (oily/waxy) sebum to inhibit inflammatory cytokines that cause hair follicle dormancy. I wrote the first hypothesis that this worked back in the 90's and a couple years later a study confirmed it and then several others over the next few years.

 

However, there are a number of other agents that combined yield greater benefits, as you can read at: http://www.michaelmooney.net/hair.html

 

I assume that there are several other agents that are effective. However, I basically quit researching the topic after experiencing some success.

 

However, one thing that isn't in that article that I believe has further improved my hair quality - C60 fullerene.

 

I've been taking 7 mg/day of C60oo since August, 2012, after reading Turnbuckle's experience with hair growth.

 

You can read about it on the forum on Longecity, titled c60-experiments-home/

 

 

Edited by Phoenicis, 14 April 2014 - 02:19 PM.

[mikey]

What's up Turnbuckle?

 

I need to try C60 some time, out of interest - what happens when you mix the oil with curcumin? Do the fullerenes interact with the curcumim in terms of bioavailability?

 

Take a look at this one--http://www.google.co...9114089A2?cl=en

 

Hi Mikey?

 

I had a look at you page and totally agree - I've been taking those supplements like iron to maje sure I'm not deficient. You think deficiency causes hair loss? I thought it was sex hormones. Did all of those things work for you or was it the c-60?

 

Your first post said, "The only thing thats helped me so far is nizoral."

 

Nizoral does penetrate (oily/waxy) sebum to inhibit inflammatory cytokines that cause hair follicle dormancy. I wrote the first hypothesis that this worked back in the 90's and a couple years later a study confirmed it and then several others over the next few years.

 

However, there are a number of other agents that combined yield greater benefits, as you can read at: http://www.michaelmooney.net/hair.html

 

I assume that there are several other agents that are effective. However, I basically quit researching the topic after experiencing some success.

 

However, one thing that isn't in that article that I believe has further improved my hair quality - C60 fullerene.

 

I've been taking 7 mg/day of C60oo since August, 2012, after reading Turnbuckle's experience with hair growth.

 

You can read about it on the forum on Longecity, titled c60-experiments-home/

 

 

 

All the things in my article worked for me, especially the iron and the tocotrienols.

 

Note with iron, one wants their ferritin to measure between at least 50, better 70 and 150 ng/ml. Too little or too much are not desirable. 

 

C60 just appears to have carried the improvements forward another step or two.

[Logic]

Preventable effect of L-threonate, an ascorbate metabolite, on androgen-driven balding via repression of dihydrotestosterone-induced dickkopf-1 expression in human hair dermal papilla cells.

http://www.ncbi.nlm....pubmed/21034532

 

More info here:

http://www.longecity...osteoarthritis/

 

 

"...research found PGD2 prevents hair growth, and mice that were genetically inclined to produce higher levels of PGD2 had inhibited hair growth. The research also found PGD2 levels were much higher in balding scalp tissue than nonbalding scalp tissue. The paper suggested one of the receptors involved in production of PGD2, GPR44, would therefore be a therapeutic targets for androgenic alopecia in both men and women with hair loss and thinning..."

http://en.wikipedia....rostaglandin_D2

 

"...aspirin reduced only PGD2 by 86%..."

http://www.ncbi.nlm....pubmed/18223672

 

More here:

http://www.longecity...n-for-hairloss/

 

So much for the theory;  what I have been doing is adding aspirin to my shampoo and taking 81mg daily with vit C.  

Vit C negates the negative effects of aspirin in the gut and see the 1st link about ascorbate metabolite L-Threonate....

 

This seems to be effective as my hairline has stopped receding.

 

I am also doing the Rooibos tea thing to slow/stop greying:

http://www.longecity...-greying/page-2

I drink the tea and then use the teabag to apply some topically to my temples.

This too seems to be helping, but maybe its all in my head...  

[Phoenicis]

Preventable effect of L-threonate, an ascorbate metabolite, on androgen-driven balding via repression of dihydrotestosterone-induced dickkopf-1 expression in human hair dermal papilla cells.

http://www.ncbi.nlm....pubmed/21034532

 

More info here:

http://www.longecity...osteoarthritis/

 

 

"...research found PGD2 prevents hair growth, and mice that were genetically inclined to produce higher levels of PGD2 had inhibited hair growth. The research also found PGD2 levels were much higher in balding scalp tissue than nonbalding scalp tissue. The paper suggested one of the receptors involved in production of PGD2, GPR44, would therefore be a therapeutic targets for androgenic alopecia in both men and women with hair loss and thinning..."

http://en.wikipedia....rostaglandin_D2

 

"...aspirin reduced only PGD2 by 86%..."

http://www.ncbi.nlm....pubmed/18223672

 

More here:

http://www.longecity...n-for-hairloss/

 

So much for the theory;  what I have been doing is adding aspirin to my shampoo and taking 81mg daily with vit C.  

Vit C negates the negative effects of aspirin in the gut and see the 1st link about ascorbate metabolite L-Threonate....

 

This seems to be effective as my hairline has stopped receding.

 

I am also doing the Rooibos tea thing to slow/stop greying:

http://www.longecity...-greying/page-2

I drink the tea and then use the teabag to apply some topically to my temples.

This too seems to be helping, but maybe its all in my head...  

 

 

Thanks man, would a magnesium threonate supplement work for dickkopf-1 and PGD2? Are you applying his to your scalp or are you taking it orally? How are you preparing your mixture? There does also seem to be an issue with 'inhibiting' dickkopf-1, if that is what is even going to happen. See quote from here bellow.

 

 

I did and found a number of links indicating it suppresses cancer as well as this one indiciating it promotes it. Kindly make a case for your position rather than toss out "google it."

The better question is what are the long-term implications of inhibiting a protein that appears to be directly involved tumor suppression via WNT. Since when is supplementing or initiating an intervention innocent until proven guilty?

http://www.ncbi.nlm....pubmed/22420644

Look at that abstract. Just one of several cancers that DKK1 is implicated in suppressing. You are telling me that a person should just throw caution to the wind and start inhibiting that pathway on a LT basis?

My position is "do no harm" first, then supplement second.

 

 

Edited by Phoenicis, 16 April 2014 - 09:52 PM.

[Phoenicis]

1)

 

Regarding aspirin, one response by 1kgcoffee in the thread that you linked was correct in stating that aspirin "stops prostaglan formation by inhibiting COX". I am still trying to figure out what the consensus on aspirin use is here. I am not sure if the low dose coated aspirins would produce the same effect as the regular 350mg tablets.

 

2)

 

On the topic of salicylic acid - this can be found cheaply in powdered dry form, I use 2% salicylic acid pads for my face and to treat ingrown hairs. The tricky bit could be mixing the concentration right so you dont burn yourself. It does tend to sting even at a 2% concentration.

 

3)

 

That L-threonate study that you linked does indeed indicate DKK-1 inhibition:  "Collectively, these results indicate that L-threonate inhibited DKK-1 expression in DPCs and therefore is a good treatment for the prevention of androgen-driven balding."

 

So that should be considered in light of possible adverse consequences for cancer. It makes me wonder about the accounts I've read of life-extensionists dying overwhelmingly from cancer since not to long ago vitamin-C (ascorbate) mega-dosing was common (and likely still is). At any rate it makes me wonder whether topical application of l-threonate (not ascorbate) might produce a result, perhaps a salicytic acid combo help with penetration? The point being to avoid having it spread to unwanted areas of the body? I may be wrong about the risk, again I am not a doctor, the quote at the end of this post cites studies that seem to show that l-threonate is safe.

 

There are also some negatives for the skin: http://www.ncbi.nlm....pubmed/19675559

 

4)

 

Rooibos sounds interesting, drinking the tea may be your best bet to raise catalase:

Rooibos (< i> Aspalathus linearis</i>) beyond the farm gate: From herbal tea to potential phytopharmaceutical

E Joubert, D De Beer - South African Journal of Botany, 2011 - Elsevier:

 

"Scientific studies in the public domain dealing with the topical/cosmetic applicationof rooibos extract are, however, very limited. The role ofaspalathin, the major rooibos flavonoid and antioxidant, has notyet been clarified. Poor penetration of the skin by aspalathin hasbeen demonstrated byHuang et al. (2008a). An anti-wrinkleeffect was demonstrated for a formulation containing rooibosand tea (Camellia sinensis)(Chuarienthong et al., 2010). Sincerooibos extract was not tested alone it is not possible to makeconclusions about its efficacy as an anti-wrinkle agent.According toGlynn (2010)the topical application of an herbalmixture, containing green rooibos extract, alleviates malepattern baldness. A recent US patent application deals withthe protective effect of rooibos extract against hair colour loss(Joppe et al., 2009)."

 

5)

 

I read the full version of the study on Thai plants that I linked earlier and was very intruiged. They compared the 5α-reductase inhibiting qualities and hair growth promotion of plants like Phyllanthus emblica L (Indian Gooseberry) , compared to finasteride and minoxidil, respectively.

 

"The plant extracts showed strong relationships between 5α-reductase inhibitory and hair growth promoting activity, and between 5α-reductase inhibition and the number of hair follicles. This indicates that plant extracts may be beneficial as an alternative medicine. Our group focused on using plant extracts as cosmeceuticals for prevention and treatment of hair loss. To achieve a practical alternative topical treatment for hair loss, Carthamus tinctorius is currently being developed as a suitable hair formulation, using nanoparticles to deliver active substances directly to the hair follicles."

 

"The three plants with the highest 5αR inhibitory activity, Carthamus tinctorius, Phyllanthus emblica and Clitorea ternatea, were further tested for hair growth promoting activity ( Fig. 1). At day 28, it was found that Carthamus tinctorius demonstrated the highest hair growth promoting activity, followed by Clitorea ternatea and Phyllanthus emblica. As shown in Fig. 1, the normal hair growth rate of the mice was seen in the vehicle curve. In minoxidil-treated mice, it was found that minoxidil constantly promote hair growth of the mice. Plant extracts can promote the hair growth during the first 14 days of the experiment, while during the last 14 days the hair growth rates were constant. Among these extracts, Carthamus tinctorius had the highest hair growth promoting activity. Additionally, Phyllanthus emblica and Clitorea ternatea did not show any difference in hair growth rate increment in the first 14 days, but over the last 14 days Clitorea ternatea tended to increase the hair growth rate more than Phyllanthus emblica. There was a strong correlation between FEA value and hair growth promoting activity (r = 0.719) at day 14 of the treatment."

 

6)

 

Some results on cucrumin, I've found posts in other forums that might explain how this is helpful:

 

Curcumin activates Wnt/β-catenin signaling pathway through inhibiting the activity of GSK-3β in APPswe transfected SY5Y cells.

 

Natural derivatives of curcumin attenuate the Wnt/beta-catenin pathway through down-regulation of the transcriptional coactivator p300.

 

 

From Flynn om HairLossHelpForum:

 

"Here's my citation log:

DHT > DKK-1:

http://www.nature.co.../5700999a.html

"A co-culture system using outer root sheath (ORS) keratinocytes and DP cells showed that DHT inhibits the growth of ORS cells, and neutralizing antibody against DKK-1 significantly reversed the growth inhibition of ORS cells."

http://www.bmbreport...EzMiUyOS5wZGY=

"We observed via RT-PCR analysis and enzyme-linked immunosorbent assay that DHT-induced DKK-1 expression was attenuated in the presence of L-threonate. We also found that DHT-induced activation of DKK-1 promoter activity was significantly repressed by L-threonate. Moreover, a co-culture system featuring outer root sheath (ORS) keratinocytes and DPCs showed that DHT inhibited the growth of ORS cells, which was then significantly reversed by L-threonate. Collectively, these results indicate that L-threonate inhibited DKK-1 expression in DPCs and therefore is a good treatment for the prevention of androgen-driven balding."


DKK-1 > WNT:

http://www.touchbrie...3196/walker.pdf

"Dickkopf family members (Dkk1 and Dkk2) and secreted frizzled related proteins (Sfrps) are families of extracellular proteins that negatively modulate canonical Wnt signalling."

http://www.sciencedi...56328206004078

"More widespread Dkk1 expression (driven by the Col1A1 3.6 kb promoter) yielded osteopenia with forelimb deformities and hairlessness,"

WNT - LGR5:

http://www.ncbi.nlm....ubmed/22991440

"The structures of the outer layer and of the bulb, which ensures HF growth, have not been completely established. To clarify these points, we have conducted in vivo clonal analyses with 3D imaging in mice. ... Furthermore, we describe an additional element, the bulb outer layer, which is contiguous and shares markers (e.g. Lgr5) with the basal ORS but is formed by a separate lineage that belongs neither to the ORS nor Cp lineage."

http://www.sciencedi...34590908005766

"Jaks et al. used elegant in vivo lineage tracing experiments to show that Lgr5+ cells give rise to all cell lineages of the hair follicle below the sebaceous gland; contribution to the sebaceous gland was only found in transplantation experiments, which may not reflect the physiological role of these cells. Assuming there was no leakiness in the lineage-tracing experiments, Lgr5-derived cells persist for at least 14 months, indicating that Lgr5+ cells are long lived, consistent with their function as true stem cells."

http://www.ncbi.nlm....ubmed/22787049

"Lgr5-expressing supporting cells, sorted by flow cytometry and cultured in a single-cell suspension, compared with unsorted cells, displayed an enhanced capacity for self-renewing neurosphere formation in response to Wnt and were converted to hair cells at a higher (>10-fold) rate. The greater differentiation of hair cells in the neurosphere assay showed that Lgr5-positive cells had the capacity to act as cochlear progenitor cells, and lineage tracing confirmed that Lgr5-expressing cells accounted for the cells that formed neurospheres and differentiated to hair cells."

http://www.ncbi.nlm....pubmed/23190887

"A signal first arising in the dermis to initiate the development of hair follicles has been described for many decades. Wnt is the earliest signal known to be intimately involved in hair follicle induction."

WNT > GSK3 > SMAD1:

http://www.ncbi.nlm....les/PMC2200633/

"In the present study we demonstrate that phosphorylation at the GSK3 sites represses the transcriptional activity of Smad1 by enhancing proteasomal degradation of pSmad1Cter."

http://www.hhmi.ucla...rs_CGFR_09.pdf

"Phosphorylation of Smad1 by MAPK and GSK3 result in its polyubiquitination and transport to the centrosome where it is degraded by the proteasome. These linker phosphorylations inhibit BMP/Smad1signaling by shortening its duration. Wnt, which negatively regulates GSK3 activity, prolongs the BMP/Smad1 signal"

BMP > SMAD1 > DLX3:

http://www.nature.co.../1204117a.html

"Smad1 stained primarily in the cytoplasm of the epidermis, hair follicles, and some dermal fibroblasts (Figure 3). Although both Smad1 and -5 have been suggested to mediate BMP signaling, the staining pattern of Smad5 in the skin was different from Smad1 ... Hair follicles harbor epidermal stem cells that determine epidermal proliferation, differentiation and regeneration. Therefore, if some of these Smads have effects on hair follicles, they may potentially affect epidermal development, wound-healing and carcinogenesis."

http://researchresou...R049778-03.htm

"BMPs, noggin, Smad1 and Smad5 are broadly expressed in the hair follicle epithelium and mesenchyme during its development and cycling. However, due to embryonic lethality of the noggin, Smad1 or Smad5 knockout mice, their roles in the control of cell proliferation, differentiation and apoptosis in the hair follicle remain largely unknown. Based on our preliminary data, we hypothesize that spatial and temporal specificity of BMP effects in distinct hair follicle compartments is determined by noggin-dependent magnitude of signaling through BMP receptors and by differential recruitment of the Smad1 and Smad5 transcriptional regulators."

http://www.ncbi.nlm....pubmed/18684741

"Colocalization of phospho-Smad1/5/8 and Dlx3 is consistent with a regulatory role for BMP signaling to Dlx3 during hair morphogenesis. Importantly, mutant catagen follicles undergo delayed regression and display persistent proliferation. Moreover, ablation of Dlx3 expression in the telogen bulge stem cells is associated with a loss of BMP signaling, precluding re-initiation of the hair follicle growth cycle."

http://www.ncbi.nlm....pubmed/11788714

"Mutation of the Smad1/Smad4-binding site inhibited transcriptional activation of the Dlx3 gene by BMP-2. In the hair follicle, where Dlx3 is expressed in the hair matrix cells, BMP-2 also activates Dlx3 transcription. These results provide a possible mechanism of action for the BMP signaling pathway on the regulation of Dlx3."

DLX3 > Hair:

http://www.ncbi.nlm....pubmed/18492670

"This transcription factor is known to be essential for placental formation and to be involved in skin and skeletal organogenesis. In humans, a frameshift mutation in the coding sequence of the DLX3 gene results in an ectodermal dysplasia called Tricho-Dento-Osseous syndrome (TDO). The main features of this autosomal dominant disorder are defects in hair, teeth, and bone."

http://www.ncbi.nlm....pubmed/22442153

"We also found that HR down-regulated Dlx3 mRNA expression through suppression of Dlx3 promoter activity. In addition, we showed that Dlx3 regulated the expression of IRS keratins. Our results demonstrate that regulation of Dlx3 by HR affects the IRS keratin expression, thus modulating the formation of IRS of hair follicle."

WNT - MSC:

http://www.ncbi.nlm....pubmed/23124852

"In this study, we reported that the Wnt/?-catenin signaling was a potent activator of reactive oxygen species (ROS) generation in MSCs. After scavenging ROS with N-acetylcysteine, Wnt/?-catenin signaling-induced MSC aging was significantly attenuated and the DNA damage and the expression of p16(INK4A), p53, and p21 were reduced in MSCs. These results indicated that the Wnt/?-catenin signaling could induce MSC aging through promoting the intracellular production of ROS, and ROS may be the main mediators of MSC aging induced by excessive activation of Wnt/?-catenin signaling."

http://www.sciencedi...78111908006367
"This review outlines the current understanding of the distinct Wnt intracellular pathways including both canonical ?-catenin/TCF(LEF1) signaling and non-canonical cascades mediated by JNK, PKC, Ca2+ or Rho, and how they are involved in the regulation of MSC proliferation and differentiation. We also discuss the coordination between different Wnt signaling cascades to precisely control MSC cell fate decisions, and we dissect the functional cross-talk of Wnt signaling that is known to occur with other growth factor signaling pathways."

http://www.ncbi.nlm....pubmed/17546602

"We focus specifically on the involvement of low-density lipoprotein-related protein 5 (LRP5), T-cell factor 1 (TCF1), and Frizzled (Fz) receptors, in the presence or absence of exogenous, prototypical canonical (Wnt3a), and non-canonical (Wnt5a) Wnts. In undifferentiated MSCs, LRP5 and TCF1 mediate canonical Wnt signal transduction, leading to increased proliferation, enhanced synergistically by Wnt3a. However, LRP5 overexpression inhibits osteogenic differentiation, further suppressed by Wnt3a. Wnt5a does not affect cell proliferation but enhances osteogenesis of MSCs. Interestingly, Wnt5a inhibits Wnt3a effects on MSCs, while Wnt3a suppresses Wnt5a-mediated enhancement of osteogenesis."

http://aura.abdn.ac....rentiation.pdf
"Overall, canonical Wnt signaling appears to stimulate the differentiation of MSCs committed to osteogenic lineage, while it inhibits the terminal differentiation of mature osteoblasts."

DKK-1 MSC

http://www.ncbi.nlm....pubmed/15504735

"Because Wnt antagonists increase the number of non-committed hMSCs in culture, they may be of use in increasing the rate of osseous wound healing in vivo by increasing the level of systemically migrating hMSCs. Therefore, such molecules could contribute to the development of a novel family of pharmaceutical agents for the improvement of the healing process in humans."

http://www.ncbi.nlm....pubmed/15965110

"Our investigation of the role of Wnt signaling in osteogenesis by hMSCs ex vivo has demonstrated that osteogenesis proceeds in response to bone morphogenic protein 2 stimulation and is sustained by Wnt signaling. In the presence of Dkk-1, an inhibitor of Wnt signaling, the cascade is disrupted, resulting in inhibition of osteogenesis."

MSC - Paracrine Factors:

http://www.ncbi.nlm....pubmed/22188562

"Human adult mesenchymal stem cells (MSCs) support the engineering of functional tissue constructs by secreting angiogenic and cytoprotective factors, which act in a paracrine fashion to influence cell survival and vascularization. MSCs have been isolated from many different tissue sources, but little is known about how paracrine factor secretion varies between different MSC populations. We evaluated paracrine factor expression patterns in MSCs isolated from adipose tissue (ASCs), bone marrow (BMSCs), and dermal tissues [dermal sheath cells (DSCs) and dermal papilla cells (DPCs)]. Specifically, mRNA expression analysis identified insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor-D (VEGF-D), and interleukin-8 (IL-8) to be expressed at higher levels in ASCs compared with other MSC populations whereas VEGF-A, angiogenin, basic fibroblast growth factor (bFGF), and nerve growth factor (NGF) were expressed at comparable levels among the MSC populations examined. Analysis of conditioned media (CM) protein confirmed the comparable level of angiogenin and VEGF-A secretion in all MSC populations and showed that DSCs and DPCs produced significantly higher concentrations of leptin."

WNT3a - BMP-2:

http://www.ncbi.nlm....pubmed/22213482

"Meanwhile, we also found that Wnt3a treatment strongly stimulated Bmp-2 expression, and that the subsequent increase in Bmp-2 protein was determined in Wnt3a-treated conditioned medium (CM). Treatment of MC3T3-E1 cells with CM stimulated phosphorylation of the Smad1/5 proteins and their downstream Dlx5 mRNA expression. The CM-mediated increases of phospho-Smad and Dlx5 expression were not blocked completely by a Wnt3a antagonist, Dkk-1, but were almost completely suppressed by the addition of a Bmp-2 antagonist, Noggin. Collectively, Wnt3a stimulates Mepe transcription directly by a canonical Wnt signaling pathway through ?-catenin and Lef-1 and indirectly through the activation of a Bmp-2 autocrine loop."

http://www.ncbi.nlm....pubmed/14584895

"Wnt3a-mediated ALP induction was inhibited by overexpression of either Xddl, dickkopf 1 (dkk1), or LRP5deltaC, indicating that canonical beta-catenin signaling is responsible for this activity. The use of Noggin, a bone morphogenic protein (BMP) inhibitor, or cyclopamine, a Hedgehog inhibitor, revealed that the induction of ALP by Wnt is independent of these morphogenetic proteins and does not require de novo protein synthesis. In contrast, blocking Wnt/LRP5 signaling or protein synthesis inhibited the ability of both BMP-2 and Shh to induce ALP in mesenchymal cells. Moreover, BMP-2 enhanced Wntl and Wnt3a expression in our cells. In MC3T3-E1 cells, where endogenous ALP levels are maximal, antagonizing the Wnt/LRP5 pathway led to a decrease of ALP activity. In addition, overexpression of dkkl reduced extracellular matrix mineralization in a BMP-2-dependent assay."

WNT3a - HF Melanin:

http://www.ncbi.nlm....pubmed/22465131

"By using melanocyte-targeted Dct-LacZ transgenic mice, we found that Wnt3a signaling is activated in mouse HF melanocytes during anagen of hair cycle. To further explore the potential functions of Wnt3a in mouse melanocytes, we infected melan-a cells with AdWnt3a to serve as the production source of Wnt3a protein. We demonstrated that Wnt3a promoted melanogenesis through upregulation of MITF and its downstream genes, tyrosinase and TRP1, in melanocytes. In vivo, AdWnt3a rescued the effects of AdsimMITF on HF melanocytes and promoted melanin synthesis."

http://www.ncbi.nlm....pubmed/22710324

"We infected melan-a cells with AdWnt3a to serve as the production source of the Wnt3a protein. MTT assay, 5-bromodeoxyuridine incorporation assay and flow cytometric analysis showed that Wnt3a inhibited the proliferation of melan-a cells and this was associated with decrease of cells in the S phase and increase of cells in the G(1) phase. Melanin content and tyrosinase activity assay revealed that Wnt3a significantly promoted melanogenesis of melan-a cells. Furthermore, western blot analysis showed that Wnt3a upregulated the expression of microphthalmia-associated transcription factor and its downstream target genes, tyrosinase and tyrosinase-related protein 1 in melan-a cells."

http://www.ncbi.nlm....pubmed/16354197

"Melanin synthesis in the hair follicle (HF) is strictly coupled to the growth stage of the hair cycle and is interrupted during follicle regression (catagen) and resting. ... During late catagen, TUNEL and Ki-67 negative melanocytes expressing Bcl-2 are seen in the secondary germ of the HF. Lack of proliferation in the follicular melanocytes during catagen suggests that secondary hair germ of late catagen HF is most likely repopulated by melanocytes arising from the outer root sheath or follicular papilla of early/mid-catagen HF. Taken together, these data suggest a possible scenario and mechanisms of the remodeling of the follicular pigmentary unit during HF anagen-catagen-telogen transition and may be used for the establishing in vivo models for pharmacological modulation of melanocyte apoptosis and survival during the hair cycle."

WNT - PGE2:

http://www.cell.com/...34590909001076

"WNT and PGE2 signaling pathways are each associated with stem cell activity in the hematopoietic system. In a recent issue of Cell, Goessling et al. (2009) use the zebrafish model to reveal a conserved PKA-dependent mechanism that connects the two pathways via ?-catenin, enhancing stem cell proliferation and tissue regeneration."

WNT3a > Caspase:

"We examined the effect of Wnt3a and Sfrp2 on HR-induced apoptosis. Wnt3a significantly increased cellular caspase activities and TUNEL staining in response to HR. Sfrp2 attenuated significantly Wnt3a-induced caspase activities in a concentration dependent fashion. Using a solid phase binding assay, our data demonstrates that Sfrp2 physically binds to Wnt3a. In addition, we observed that Sfrp2 dramatically inhibits the beta-catenin/TCF transcriptional activities induced by Wnt3a. Impressively, Dickkopf-1, a protein that binds to the Wnt coreceptor LRP, significantly inhibited the Wnt3a-activated caspase and transcriptional activities."

LPGDS - GSK3:

http://www.ncbi.nlm....term=gsk3 lpgds

"Furthermore, we examined the effect of L-PGDS incubation on insulin-stimulated Akt, glycogen synthase kinase-3beta (GSK-3beta), and ERK phosphorylation. Unexpectedly, we found that when WKY cells were pretreated with L-PGDS, insulin could actually induce apoptosis and failed to stimulate Akt/GSK-3beta phosphorylation. Insulin-stimulated ERK phosphorylation was unaffected by L-PGDS pretreatment in both cell lines."

Threonate:
http://www.ncbi.nlm....pubmed/21986570
"Calcium L-threonate was well tolerated in healthy Chinese subjects, with no pattern of dose-related adverse events. Plasma exposure increased with dose escalation, but linear pharmacokinetics were not observed over the studied doses. L-threonate was absorbed rapidly, and its absorption was enhanced by food intake. No systemic accumulation appeared after repeated administrations."
http://www.ncbi.nlm....pubmed/16554191
http://www.ncbi.nlm....pubmed/23229796
http://www.ncbi.nlm....pubmed/23229796
http://www.ncbi.nlm....pubmed/20152124


ASC-2P:

http://www.springerl...502h52x1132l1/

Disclaimer: I'm not a doctor. Please do not use this to support any diagnoses or treatments."

 

 

 

Preventable effect of L-threonate, an ascorbate metabolite, on androgen-driven balding via repression of dihydrotestosterone-induced dickkopf-1 expression in human hair dermal papilla cells.

http://www.ncbi.nlm....pubmed/21034532

 

More info here:

http://www.longecity...osteoarthritis/

 

 

"...research found PGD2 prevents hair growth, and mice that were genetically inclined to produce higher levels of PGD2 had inhibited hair growth. The research also found PGD2 levels were much higher in balding scalp tissue than nonbalding scalp tissue. The paper suggested one of the receptors involved in production of PGD2, GPR44, would therefore be a therapeutic targets for androgenic alopecia in both men and women with hair loss and thinning..."

http://en.wikipedia....rostaglandin_D2

 

"...aspirin reduced only PGD2 by 86%..."

http://www.ncbi.nlm....pubmed/18223672

 

More here:

http://www.longecity...n-for-hairloss/

 

So much for the theory;  what I have been doing is adding aspirin to my shampoo and taking 81mg daily with vit C.  

Vit C negates the negative effects of aspirin in the gut and see the 1st link about ascorbate metabolite L-Threonate....

 

This seems to be effective as my hairline has stopped receding.

 

I am also doing the Rooibos tea thing to slow/stop greying:

http://www.longecity...-greying/page-2

I drink the tea and then use the teabag to apply some topically to my temples.

This too seems to be helping, but maybe its all in my head...  

 

 

Edited by Phoenicis, 17 April 2014 - 07:33 PM.

[LexLux]

Those two curcumin studies seem to contradict each other, but if the former is correct WNT beta may be a possible target. Could upregulating WNT beta (supressed by DKK-1) avoid the worry of having to use DKK-1 inhibition and promoting cancer?

1)

 

Regarding aspirin, one response by 1kgcoffee in the thread that you linked was correct in stating that aspirin "stops prostaglan formation by inhibiting COX". I am still trying to figure out what the consensus on aspirin use is here. I am not sure if the low dose coated aspirins would produce the same effect as the regular 350mg tablets.

 

2)

 

On the topic of salicylic acid - this can be found cheaply in powdered dry form, I use 2% salicylic acid pads for my face and to treat ingrown hairs. The tricky bit could be mixing the concentration right so you dont burn yourself. It does tend to sting even at a 2% concentration.

 

3)

 

That L-threonate study that you linked does indeed indicate DKK-1 inhibition:  "Collectively, these results indicate that L-threonate inhibited DKK-1 expression in DPCs and therefore is a good treatment for the prevention of androgen-driven balding."

 

So that should be considered in light of possible adverse consequences for cancer. It makes me wonder about the accounts I've read of life-extensionists dying overwhelmingly from cancer since not to long ago vitamin-C (ascorbate) mega-dosing was common (and likely still is). At any rate it makes me wonder whether topical application of l-threonate (not ascorbate) might produce a result, perhaps a salicytic acid combo help with penetration? The point being to avoid having it spread to unwanted areas of the body? I may be wrong about the risk, again I am not a doctor, the quote at the end of this post cites studies that seem to show that l-threonate is safe.

 

There are also some negatives for the skin: http://www.ncbi.nlm....pubmed/19675559

 

4)

 

Rooibos sounds interesting, drinking the tea may be your best bet to raise catalase:

Rooibos (< i> Aspalathus linearis</i>) beyond the farm gate: From herbal tea to potential phytopharmaceutical

E Joubert, D De Beer - South African Journal of Botany, 2011 - Elsevier:

 

"Scientific studies in the public domain dealing with the topical/cosmetic applicationof rooibos extract are, however, very limited. The role ofaspalathin, the major rooibos flavonoid and antioxidant, has notyet been clarified. Poor penetration of the skin by aspalathin hasbeen demonstrated byHuang et al. (2008a). An anti-wrinkleeffect was demonstrated for a formulation containing rooibosand tea (Camellia sinensis)(Chuarienthong et al., 2010). Sincerooibos extract was not tested alone it is not possible to makeconclusions about its efficacy as an anti-wrinkle agent.According toGlynn (2010)the topical application of an herbalmixture, containing green rooibos extract, alleviates malepattern baldness. A recent US patent application deals withthe protective effect of rooibos extract against hair colour loss(Joppe et al., 2009)."

 

5)

 

I read the full version of the study on Thai plants that I linked earlier and was very intruiged. They compared the 5α-reductase inhibiting qualities and hair growth promotion of plants like Phyllanthus emblica L (Indian Gooseberry) , compared to finasteride and minoxidil, respectively.

 

"The plant extracts showed strong relationships between 5α-reductase inhibitory and hair growth promoting activity, and between 5α-reductase inhibition and the number of hair follicles. This indicates that plant extracts may be beneficial as an alternative medicine. Our group focused on using plant extracts as cosmeceuticals for prevention and treatment of hair loss. To achieve a practical alternative topical treatment for hair loss, Carthamus tinctorius is currently being developed as a suitable hair formulation, using nanoparticles to deliver active substances directly to the hair follicles."

 

"The three plants with the highest 5αR inhibitory activity, Carthamus tinctorius, Phyllanthus emblica and Clitorea ternatea, were further tested for hair growth promoting activity ( Fig. 1). At day 28, it was found that Carthamus tinctorius demonstrated the highest hair growth promoting activity, followed by Clitorea ternatea and Phyllanthus emblica. As shown in Fig. 1, the normal hair growth rate of the mice was seen in the vehicle curve. In minoxidil-treated mice, it was found that minoxidil constantly promote hair growth of the mice. Plant extracts can promote the hair growth during the first 14 days of the experiment, while during the last 14 days the hair growth rates were constant. Among these extracts, Carthamus tinctorius had the highest hair growth promoting activity. Additionally, Phyllanthus emblica and Clitorea ternatea did not show any difference in hair growth rate increment in the first 14 days, but over the last 14 days Clitorea ternatea tended to increase the hair growth rate more than Phyllanthus emblica. There was a strong correlation between FEA value and hair growth promoting activity (r = 0.719) at day 14 of the treatment."

 

6)

 

Some results on cucrumin, I've found posts in other forums that might explain how this is helpful:

 

Curcumin activates Wnt/β-catenin signaling pathway through inhibiting the activity of GSK-3β in APPswe transfected SY5Y cells.

 

Natural derivatives of curcumin attenuate the Wnt/beta-catenin pathway through down-regulation of the transcriptional coactivator p300.

 

 

From Flynn om HairLossHelpForum:

 

"Here's my citation log:

DHT > DKK-1:

http://www.nature.co.../5700999a.html

"A co-culture system using outer root sheath (ORS) keratinocytes and DP cells showed that DHT inhibits the growth of ORS cells, and neutralizing antibody against DKK-1 significantly reversed the growth inhibition of ORS cells."

http://www.bmbreport...EzMiUyOS5wZGY=

"We observed via RT-PCR analysis and enzyme-linked immunosorbent assay that DHT-induced DKK-1 expression was attenuated in the presence of L-threonate. We also found that DHT-induced activation of DKK-1 promoter activity was significantly repressed by L-threonate. Moreover, a co-culture system featuring outer root sheath (ORS) keratinocytes and DPCs showed that DHT inhibited the growth of ORS cells, which was then significantly reversed by L-threonate. Collectively, these results indicate that L-threonate inhibited DKK-1 expression in DPCs and therefore is a good treatment for the prevention of androgen-driven balding."


DKK-1 > WNT:

http://www.touchbrie...3196/walker.pdf

"Dickkopf family members (Dkk1 and Dkk2) and secreted frizzled related proteins (Sfrps) are families of extracellular proteins that negatively modulate canonical Wnt signalling."

http://www.sciencedi...56328206004078

"More widespread Dkk1 expression (driven by the Col1A1 3.6 kb promoter) yielded osteopenia with forelimb deformities and hairlessness,"

WNT - LGR5:

http://www.ncbi.nlm....ubmed/22991440

"The structures of the outer layer and of the bulb, which ensures HF growth, have not been completely established. To clarify these points, we have conducted in vivo clonal analyses with 3D imaging in mice. ... Furthermore, we describe an additional element, the bulb outer layer, which is contiguous and shares markers (e.g. Lgr5) with the basal ORS but is formed by a separate lineage that belongs neither to the ORS nor Cp lineage."

http://www.sciencedi...34590908005766

"Jaks et al. used elegant in vivo lineage tracing experiments to show that Lgr5+ cells give rise to all cell lineages of the hair follicle below the sebaceous gland; contribution to the sebaceous gland was only found in transplantation experiments, which may not reflect the physiological role of these cells. Assuming there was no leakiness in the lineage-tracing experiments, Lgr5-derived cells persist for at least 14 months, indicating that Lgr5+ cells are long lived, consistent with their function as true stem cells."

http://www.ncbi.nlm....ubmed/22787049

"Lgr5-expressing supporting cells, sorted by flow cytometry and cultured in a single-cell suspension, compared with unsorted cells, displayed an enhanced capacity for self-renewing neurosphere formation in response to Wnt and were converted to hair cells at a higher (>10-fold) rate. The greater differentiation of hair cells in the neurosphere assay showed that Lgr5-positive cells had the capacity to act as cochlear progenitor cells, and lineage tracing confirmed that Lgr5-expressing cells accounted for the cells that formed neurospheres and differentiated to hair cells."

http://www.ncbi.nlm....pubmed/23190887

"A signal first arising in the dermis to initiate the development of hair follicles has been described for many decades. Wnt is the earliest signal known to be intimately involved in hair follicle induction."

WNT > GSK3 > SMAD1:

http://www.ncbi.nlm....les/PMC2200633/

"In the present study we demonstrate that phosphorylation at the GSK3 sites represses the transcriptional activity of Smad1 by enhancing proteasomal degradation of pSmad1Cter."

http://www.hhmi.ucla...rs_CGFR_09.pdf

"Phosphorylation of Smad1 by MAPK and GSK3 result in its polyubiquitination and transport to the centrosome where it is degraded by the proteasome. These linker phosphorylations inhibit BMP/Smad1signaling by shortening its duration. Wnt, which negatively regulates GSK3 activity, prolongs the BMP/Smad1 signal"

BMP > SMAD1 > DLX3:

http://www.nature.co.../1204117a.html

"Smad1 stained primarily in the cytoplasm of the epidermis, hair follicles, and some dermal fibroblasts (Figure 3). Although both Smad1 and -5 have been suggested to mediate BMP signaling, the staining pattern of Smad5 in the skin was different from Smad1 ... Hair follicles harbor epidermal stem cells that determine epidermal proliferation, differentiation and regeneration. Therefore, if some of these Smads have effects on hair follicles, they may potentially affect epidermal development, wound-healing and carcinogenesis."

http://researchresou...R049778-03.htm

"BMPs, noggin, Smad1 and Smad5 are broadly expressed in the hair follicle epithelium and mesenchyme during its development and cycling. However, due to embryonic lethality of the noggin, Smad1 or Smad5 knockout mice, their roles in the control of cell proliferation, differentiation and apoptosis in the hair follicle remain largely unknown. Based on our preliminary data, we hypothesize that spatial and temporal specificity of BMP effects in distinct hair follicle compartments is determined by noggin-dependent magnitude of signaling through BMP receptors and by differential recruitment of the Smad1 and Smad5 transcriptional regulators."

http://www.ncbi.nlm....pubmed/18684741

"Colocalization of phospho-Smad1/5/8 and Dlx3 is consistent with a regulatory role for BMP signaling to Dlx3 during hair morphogenesis. Importantly, mutant catagen follicles undergo delayed regression and display persistent proliferation. Moreover, ablation of Dlx3 expression in the telogen bulge stem cells is associated with a loss of BMP signaling, precluding re-initiation of the hair follicle growth cycle."

http://www.ncbi.nlm....pubmed/11788714

"Mutation of the Smad1/Smad4-binding site inhibited transcriptional activation of the Dlx3 gene by BMP-2. In the hair follicle, where Dlx3 is expressed in the hair matrix cells, BMP-2 also activates Dlx3 transcription. These results provide a possible mechanism of action for the BMP signaling pathway on the regulation of Dlx3."

DLX3 > Hair:

http://www.ncbi.nlm....pubmed/18492670

"This transcription factor is known to be essential for placental formation and to be involved in skin and skeletal organogenesis. In humans, a frameshift mutation in the coding sequence of the DLX3 gene results in an ectodermal dysplasia called Tricho-Dento-Osseous syndrome (TDO). The main features of this autosomal dominant disorder are defects in hair, teeth, and bone."

http://www.ncbi.nlm....pubmed/22442153

"We also found that HR down-regulated Dlx3 mRNA expression through suppression of Dlx3 promoter activity. In addition, we showed that Dlx3 regulated the expression of IRS keratins. Our results demonstrate that regulation of Dlx3 by HR affects the IRS keratin expression, thus modulating the formation of IRS of hair follicle."

WNT - MSC:

http://www.ncbi.nlm....pubmed/23124852

"In this study, we reported that the Wnt/?-catenin signaling was a potent activator of reactive oxygen species (ROS) generation in MSCs. After scavenging ROS with N-acetylcysteine, Wnt/?-catenin signaling-induced MSC aging was significantly attenuated and the DNA damage and the expression of p16(INK4A), p53, and p21 were reduced in MSCs. These results indicated that the Wnt/?-catenin signaling could induce MSC aging through promoting the intracellular production of ROS, and ROS may be the main mediators of MSC aging induced by excessive activation of Wnt/?-catenin signaling."

http://www.sciencedi...78111908006367
"This review outlines the current understanding of the distinct Wnt intracellular pathways including both canonical ?-catenin/TCF(LEF1) signaling and non-canonical cascades mediated by JNK, PKC, Ca2+ or Rho, and how they are involved in the regulation of MSC proliferation and differentiation. We also discuss the coordination between different Wnt signaling cascades to precisely control MSC cell fate decisions, and we dissect the functional cross-talk of Wnt signaling that is known to occur with other growth factor signaling pathways."

http://www.ncbi.nlm....pubmed/17546602

"We focus specifically on the involvement of low-density lipoprotein-related protein 5 (LRP5), T-cell factor 1 (TCF1), and Frizzled (Fz) receptors, in the presence or absence of exogenous, prototypical canonical (Wnt3a), and non-canonical (Wnt5a) Wnts. In undifferentiated MSCs, LRP5 and TCF1 mediate canonical Wnt signal transduction, leading to increased proliferation, enhanced synergistically by Wnt3a. However, LRP5 overexpression inhibits osteogenic differentiation, further suppressed by Wnt3a. Wnt5a does not affect cell proliferation but enhances osteogenesis of MSCs. Interestingly, Wnt5a inhibits Wnt3a effects on MSCs, while Wnt3a suppresses Wnt5a-mediated enhancement of osteogenesis."

http://aura.abdn.ac....rentiation.pdf
"Overall, canonical Wnt signaling appears to stimulate the differentiation of MSCs committed to osteogenic lineage, while it inhibits the terminal differentiation of mature osteoblasts."

DKK-1 MSC

http://www.ncbi.nlm....pubmed/15504735

"Because Wnt antagonists increase the number of non-committed hMSCs in culture, they may be of use in increasing the rate of osseous wound healing in vivo by increasing the level of systemically migrating hMSCs. Therefore, such molecules could contribute to the development of a novel family of pharmaceutical agents for the improvement of the healing process in humans."

http://www.ncbi.nlm....pubmed/15965110

"Our investigation of the role of Wnt signaling in osteogenesis by hMSCs ex vivo has demonstrated that osteogenesis proceeds in response to bone morphogenic protein 2 stimulation and is sustained by Wnt signaling. In the presence of Dkk-1, an inhibitor of Wnt signaling, the cascade is disrupted, resulting in inhibition of osteogenesis."

MSC - Paracrine Factors:

http://www.ncbi.nlm....pubmed/22188562

"Human adult mesenchymal stem cells (MSCs) support the engineering of functional tissue constructs by secreting angiogenic and cytoprotective factors, which act in a paracrine fashion to influence cell survival and vascularization. MSCs have been isolated from many different tissue sources, but little is known about how paracrine factor secretion varies between different MSC populations. We evaluated paracrine factor expression patterns in MSCs isolated from adipose tissue (ASCs), bone marrow (BMSCs), and dermal tissues [dermal sheath cells (DSCs) and dermal papilla cells (DPCs)]. Specifically, mRNA expression analysis identified insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor-D (VEGF-D), and interleukin-8 (IL-8) to be expressed at higher levels in ASCs compared with other MSC populations whereas VEGF-A, angiogenin, basic fibroblast growth factor (bFGF), and nerve growth factor (NGF) were expressed at comparable levels among the MSC populations examined. Analysis of conditioned media (CM) protein confirmed the comparable level of angiogenin and VEGF-A secretion in all MSC populations and showed that DSCs and DPCs produced significantly higher concentrations of leptin."

WNT3a - BMP-2:

http://www.ncbi.nlm....pubmed/22213482

"Meanwhile, we also found that Wnt3a treatment strongly stimulated Bmp-2 expression, and that the subsequent increase in Bmp-2 protein was determined in Wnt3a-treated conditioned medium (CM). Treatment of MC3T3-E1 cells with CM stimulated phosphorylation of the Smad1/5 proteins and their downstream Dlx5 mRNA expression. The CM-mediated increases of phospho-Smad and Dlx5 expression were not blocked completely by a Wnt3a antagonist, Dkk-1, but were almost completely suppressed by the addition of a Bmp-2 antagonist, Noggin. Collectively, Wnt3a stimulates Mepe transcription directly by a canonical Wnt signaling pathway through ?-catenin and Lef-1 and indirectly through the activation of a Bmp-2 autocrine loop."

http://www.ncbi.nlm....pubmed/14584895

"Wnt3a-mediated ALP induction was inhibited by overexpression of either Xddl, dickkopf 1 (dkk1), or LRP5deltaC, indicating that canonical beta-catenin signaling is responsible for this activity. The use of Noggin, a bone morphogenic protein (BMP) inhibitor, or cyclopamine, a Hedgehog inhibitor, revealed that the induction of ALP by Wnt is independent of these morphogenetic proteins and does not require de novo protein synthesis. In contrast, blocking Wnt/LRP5 signaling or protein synthesis inhibited the ability of both BMP-2 and Shh to induce ALP in mesenchymal cells. Moreover, BMP-2 enhanced Wntl and Wnt3a expression in our cells. In MC3T3-E1 cells, where endogenous ALP levels are maximal, antagonizing the Wnt/LRP5 pathway led to a decrease of ALP activity. In addition, overexpression of dkkl reduced extracellular matrix mineralization in a BMP-2-dependent assay."

WNT3a - HF Melanin:

http://www.ncbi.nlm....pubmed/22465131

"By using melanocyte-targeted Dct-LacZ transgenic mice, we found that Wnt3a signaling is activated in mouse HF melanocytes during anagen of hair cycle. To further explore the potential functions of Wnt3a in mouse melanocytes, we infected melan-a cells with AdWnt3a to serve as the production source of Wnt3a protein. We demonstrated that Wnt3a promoted melanogenesis through upregulation of MITF and its downstream genes, tyrosinase and TRP1, in melanocytes. In vivo, AdWnt3a rescued the effects of AdsimMITF on HF melanocytes and promoted melanin synthesis."

http://www.ncbi.nlm....pubmed/22710324

"We infected melan-a cells with AdWnt3a to serve as the production source of the Wnt3a protein. MTT assay, 5-bromodeoxyuridine incorporation assay and flow cytometric analysis showed that Wnt3a inhibited the proliferation of melan-a cells and this was associated with decrease of cells in the S phase and increase of cells in the G(1) phase. Melanin content and tyrosinase activity assay revealed that Wnt3a significantly promoted melanogenesis of melan-a cells. Furthermore, western blot analysis showed that Wnt3a upregulated the expression of microphthalmia-associated transcription factor and its downstream target genes, tyrosinase and tyrosinase-related protein 1 in melan-a cells."

http://www.ncbi.nlm....pubmed/16354197

"Melanin synthesis in the hair follicle (HF) is strictly coupled to the growth stage of the hair cycle and is interrupted during follicle regression (catagen) and resting. ... During late catagen, TUNEL and Ki-67 negative melanocytes expressing Bcl-2 are seen in the secondary germ of the HF. Lack of proliferation in the follicular melanocytes during catagen suggests that secondary hair germ of late catagen HF is most likely repopulated by melanocytes arising from the outer root sheath or follicular papilla of early/mid-catagen HF. Taken together, these data suggest a possible scenario and mechanisms of the remodeling of the follicular pigmentary unit during HF anagen-catagen-telogen transition and may be used for the establishing in vivo models for pharmacological modulation of melanocyte apoptosis and survival during the hair cycle."

WNT - PGE2:

http://www.cell.com/...34590909001076

"WNT and PGE2 signaling pathways are each associated with stem cell activity in the hematopoietic system. In a recent issue of Cell, Goessling et al. (2009) use the zebrafish model to reveal a conserved PKA-dependent mechanism that connects the two pathways via ?-catenin, enhancing stem cell proliferation and tissue regeneration."

WNT3a > Caspase:

"We examined the effect of Wnt3a and Sfrp2 on HR-induced apoptosis. Wnt3a significantly increased cellular caspase activities and TUNEL staining in response to HR. Sfrp2 attenuated significantly Wnt3a-induced caspase activities in a concentration dependent fashion. Using a solid phase binding assay, our data demonstrates that Sfrp2 physically binds to Wnt3a. In addition, we observed that Sfrp2 dramatically inhibits the beta-catenin/TCF transcriptional activities induced by Wnt3a. Impressively, Dickkopf-1, a protein that binds to the Wnt coreceptor LRP, significantly inhibited the Wnt3a-activated caspase and transcriptional activities."

LPGDS - GSK3:

http://www.ncbi.nlm....term=gsk3 lpgds

"Furthermore, we examined the effect of L-PGDS incubation on insulin-stimulated Akt, glycogen synthase kinase-3beta (GSK-3beta), and ERK phosphorylation. Unexpectedly, we found that when WKY cells were pretreated with L-PGDS, insulin could actually induce apoptosis and failed to stimulate Akt/GSK-3beta phosphorylation. Insulin-stimulated ERK phosphorylation was unaffected by L-PGDS pretreatment in both cell lines."

Threonate:
http://www.ncbi.nlm....pubmed/21986570
"Calcium L-threonate was well tolerated in healthy Chinese subjects, with no pattern of dose-related adverse events. Plasma exposure increased with dose escalation, but linear pharmacokinetics were not observed over the studied doses. L-threonate was absorbed rapidly, and its absorption was enhanced by food intake. No systemic accumulation appeared after repeated administrations."
http://www.ncbi.nlm....pubmed/16554191
http://www.ncbi.nlm....pubmed/23229796
http://www.ncbi.nlm....pubmed/23229796
http://www.ncbi.nlm....pubmed/20152124


ASC-2P:

http://www.springerl...502h52x1132l1/

Disclaimer: I'm not a doctor. Please do not use this to support any diagnoses or treatments."

 

 

 

Preventable effect of L-threonate, an ascorbate metabolite, on androgen-driven balding via repression of dihydrotestosterone-induced dickkopf-1 expression in human hair dermal papilla cells.

http://www.ncbi.nlm....pubmed/21034532

 

More info here:

http://www.longecity...osteoarthritis/

 

 

"...research found PGD2 prevents hair growth, and mice that were genetically inclined to produce higher levels of PGD2 had inhibited hair growth. The research also found PGD2 levels were much higher in balding scalp tissue than nonbalding scalp tissue. The paper suggested one of the receptors involved in production of PGD2, GPR44, would therefore be a therapeutic targets for androgenic alopecia in both men and women with hair loss and thinning..."

http://en.wikipedia....rostaglandin_D2

 

"...aspirin reduced only PGD2 by 86%..."

http://www.ncbi.nlm....pubmed/18223672

 

More here:

http://www.longecity...n-for-hairloss/

 

So much for the theory;  what I have been doing is adding aspirin to my shampoo and taking 81mg daily with vit C.  

Vit C negates the negative effects of aspirin in the gut and see the 1st link about ascorbate metabolite L-Threonate....

 

This seems to be effective as my hairline has stopped receding.

 

I am also doing the Rooibos tea thing to slow/stop greying:

http://www.longecity...-greying/page-2

I drink the tea and then use the teabag to apply some topically to my temples.

This too seems to be helping, but maybe its all in my head...  

 

 

 

Edited by LexLux, 17 April 2014 - 09:50 PM.

[Logic]

Magnesium Threonate will work for dickkopf-1.
I use C-Ester as a by product of metabolising Ascorbate is L-Threonate
This is cheaper than Magnesium L-Threonate wich is unavailable here in South Africa anyway.

I take this orrally obviously as its the only way to get ascorbate changed into L-Threonate.

(I do take a seperate magnesium supp, but the magnesium has nothing to with the subject at hand; its simply good to suppliment it for a number of other reasons, and almost everyone is low on magnesium)

I am aware of the increased cancer risk, but follow a regimin designed to both slow aging and prevent cancer based on the information here:
http://www.anti-agin...ls.com/2013/05/
Part 1;2 and 3

I have also cured 2 cases of cancer, so am not worried about the concern around inhibiting dickkopf-1.
http://www.longecity...-cancer-in-dog/

I dont think L-Threonate will have an effect on PGD2, but have not looked for any litrature on the subject.

I have the enteric coated Aspirin at my disposal so what I do is pop 4 into a glass of water untill th orange sweet layer is dissolved.
I then crush em with a morter and pestle and remove the enteric coating that tends to stay in one piec during this process.
I started with 2 of these asperin in a medium sized bottle of Head & Shoulders shampoo (for the silicone in it) and slowly worked my way up to 4 aspirin per bottle of shampoo with no undesirable side effects so far.

I also add plain old instant coffee to the shamppo based on further info on caffine beig good for hair growth, as well as some other things.

[celebes]

Ester-C is 3% Calcium Threonate. You'd be better off with regular old Ascorbic. The vast majority is oxidized/hydrolyzed to threonate eventually.

Edited by celebes, 26 April 2014 - 05:16 AM.

[Logic]

Ester-C is 3% Calcium Threonate. You'd be better off with regular old Ascorbic. The vast majority is oxidized/hydrolyzed to threonate eventually.

 
I may have it wrong but the study does say that L-Threonate is an ascorbate metabolite..?

If I remember correctly its was Niner that advised Ascorbate as a cheap alternative to Magnesium L-Threonate.

Could you elaborate on the above plz Celebs.

[celebes]

I'm glad you gave me a reason to clarify things for myself, I was a little off base earlier. 

 

First of all, Ester-C is only 1% L-Threonate, the rest of the 3% being Calcium.

 

L-Threonate is indeed a metabolite, but the main pathway that produces it (the one I was thinking of above) is dependent on Hydrogen Peroxide and Catalysis so minor under physiological conditions. Megadosing and Cu/Fe excess can tilt the balance towards that pathway, but that happens to be the very concern behind all the warnings about excess Ascorbate, so self-defeating.

 

Dehydroascorbic acid and 2,3-Diketogulonate are the primary intermediates; Hexose Monophosphate Shunt components, Oxalate, Erythrulose and other Aldoses, Sugar Acids and Alcohols make up the bulk of the end products, generally in that order. Ascorbate conjugates (methyl, sulphate, phosphate, glucuronate) are also produced, possibly for storage. The exact proportions depend on Ascorbate status and Redox balance but still haven't been fully outlined.

 

At saturation, approximately 50mg of Ascorbate is catabolised per day. There is no data I could find but 1-5mg might be a ballpark for the maximum amount of Threonate produced normally, but that is very rough. I think it's safe to say that even if I'm off by an order of magnitude, Threonate should probably be taken directly. Extraneous Ascorbate above 200mg/day is only incrementally absorbed and excreted unmetabolised so shouldn't be pertinent.

 

All in all, it seems Niner doesn't base his recommendations on much actual knowledge. Considering the amount of research it took me to figure out even this much, I can understand why.

[Logic]

I'm glad you gave me a reason to clarify things for myself, I was a little off base earlier. 

 

First of all, Ester-C is only 1% L-Threonate, the rest of the 3% being Calcium.

 

L-Threonate is indeed a metabolite, but the main pathway that produces it (the one I was thinking of above) is dependent on Hydrogen Peroxide and Catalysis so minor under physiological conditions. Megadosing and Cu/Fe excess can tilt the balance towards that pathway, but that happens to be the very concern behind all the warnings about excess Ascorbate, so self-defeating.

 

Dehydroascorbic acid and 2,3-Diketogulonate are the primary intermediates; Hexose Monophosphate Shunt components, Oxalate, Erythrulose and other Aldoses, Sugar Acids and Alcohols make up the bulk of the end products, generally in that order. Ascorbate conjugates (methyl, sulphate, phosphate, glucuronate) are also produced, possibly for storage. The exact proportions depend on Ascorbate status and Redox balance but still haven't been fully outlined.

 

At saturation, approximately 50mg of Ascorbate is catabolised per day. There is no data I could find but 1-5mg might be a ballpark for the maximum amount of Threonate produced normally, but that is very rough. I think it's safe to say that even if I'm off by an order of magnitude, Threonate should probably be taken directly. Extraneous Ascorbate above 200mg/day is only incrementally absorbed and excreted unmetabolised so shouldn't be pertinent.

 

All in all, it seems Niner doesn't base his recommendations on much actual knowledge. Considering the amount of research it took me to figure out even this much, I can understand why.

 

Thx very much Celebes.  Great work!

 

Now where the hell do I get Magnesium L-Threonate in South Africa!?

[niner]

All in all, it seems Niner doesn't base his recommendations on much actual knowledge. Considering the amount of research it took me to figure out even this much, I can understand why.

 

Can you point out where I made this alleged pin-headed recommendation?  As far as I can tell, the closest I ever came was saying that threonate was related to ascorbate (as opposed to, say, the amino acid threonine).  I don't think I ever said that ascorbate was a good source of threonate.

[LexLux]

See the quote by abelard lindsay from this thread bellow, I think that poster had a good idea but I would not apply the Na Butyrate topically (it's used for making stink bombs), instead supplementing may be better.

 

 

A little on the hair loss story so far.

Approach 1 Lower DHT:
The standard way Propecia / 5-alpha-reductase inhibitor: bad for fertility and libido

Approach 2 Lower DKK-1:
Not possible, even if possible would bring risk of developing bone overgrowth issues.

Approach 3 B-Catenin WNT Signaling:
Tried this with topical Fo-Ti. Didn't work. Maybe taking fo-ti would work but it has too many estrogenic side effects.

Approach 4 TGF-B1 TGF-B2 IL-6:
Not possible to affect this. Even if you could, this is all immune system stuff that's not a good idea to mess with.

Approach 5 Caffeine shampoo:
Some mild success, German study says that this interferes with testosterone in hair follicles..

Which brings me to the latest idea

Approach 6: Hic-5 inhibition via hdac

Hic is expressed in hair follicles that lose hair but not in the follicles that normally don't bald (occipital scalp)
http://www.ncbi.nlm....pubmed/17508020

Quote

Androgen receptor co-activator Hic-5/ARA55 as a molecular regulator of androgen sensitivity in dermal papilla cells of human hair follicles.
Inui S, Fukuzato Y, Nakajima T, Kurata S, Itami S.
Source
Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Abstract

Androgen site-specifically affects human hair growth after puberty through androgen receptors in the dermal papilla, which transactivate target genes acting in conjunction with co-activators. To examine the regulation of androgen sensitivity in hair follicles, we focused on androgen receptor co-activator Hic-5/ARA55. Its interaction with transfected androgen receptor in beard dermal papilla cells was confirmed with mammalian two-hybrid assays. The semiquantitative reverse transcriptase-polymerase chain reaction showed that Hic-5/ARA55 mRNA expression was high in dermal papilla cells from the beard and bald frontal scalp but low in cells from the occipital scalp. To determine whether Hic-5/ARA55 mRNA level correlates with its endogenous activity, we studied the effect of dominant negative Hic-5/ARA55 on transfected androgen receptor transactivation induced by R1881 using mouse mammary tumor virus-luciferase assays. We found that it suppressed the transactivation by 64.5 and 71.4% in dermal papilla cells from the beard and bald frontal scalp, respectively, whereas it showed no significant effect in cells from the occipital scalp. Our findings suggest that Hic-5/ARA55 is a molecular regulator for androgen sensitivity in human hair follicles.

Ok so how do we turn off Hic-5 in those androgen sensitive hair follicles?

http://books.google....etylase&f=false

Quote

Further analysis showed downregulation of hic-5 upon overnight treatment with inhibitors of histone deacetylases.

So.. We have a great HDAC inhibitor in Sodium Butyrate and I've got some pills lying around that I can work into my overnight hair loss lotion. Time to get experimenting. If all this doesn't work I'll just be out some money on supplements and be forced to spend a few thousand on a hair transplant. 

Edited by abelard lindsay, 21 April 2013 - 04:43 PM.

 

Edited by LexLux, 12 May 2014 - 07:14 PM.

[Logic]

All in all, it seems Niner doesn't base his recommendations on much actual knowledge. Considering the amount of research it took me to figure out even this much, I can understand why.

 
Can you point out where I made this alleged pin-headed recommendation?  As far as I can tell, the closest I ever came was saying that threonate was related to ascorbate (as opposed to, say, the amino acid threonine).  I don't think I ever said that ascorbate was a good source of threonate.

 

Sorry Niner, my mistake.
I did say I think Niner...  so that's my only defence! 
I thought it was in the below thread that I read it, but no:
http://www.longecity...rthritis/page-2
I don't know where I got it from!?

[jsam]

Probably the most promising treatment on the horizon at the moment is cb-03-01, an androgen receptor blocker from Cosmo pharmaceuticals. Not even started testing on hair loss in any big way, but their POC got great results. It is in trials for acne at the moment, and they will be doing large scale hair loss trials after that. 

 

I know of some people using it already and getting results, so that one will be great for people if/when it hits the market 3-5 years from now.

 

Also the 2014 hair conference just finished http://www.hair2014....ents.asp?midx=4

 

It looks like a few teams working on hair follicle cloning are very close to having it cracked, but again seems like it is 5 years away from actually being available as a treatment.

[Logic]

Distinct Roles for Nerve Growth Factor and Brain-Derived Neurotrophic Factor in Controlling the Rate of Hair Follicle Morphogenesis

Increasing evidence suggests that neurotrophins play an important part in the control of the development of ectodermal derivatives, such as the hair follicle. Here, we show that, during hair follicle morphogenesis in C57BL/6 mice, nerve growth factor, brain-derived neurotrophic factor and their corresponding high-affinity tyrosine kinase receptors, TrkA and TrkB, show stringently controlled spatiotemporal expression patterns in the follicular epithelium and mesenchyme. Constitutive overexpression of nerve growth factor in mice is associated with a discrete, but significant acceleration of hair follicle morphogenesis, whereas this is not seen in brain-derived neurotrophic factor transgenic mice. In neonatal skin organ culture, nerve growth factor and brain-derived neurotrophic factor differentially influence hair follicle development: nerve growth factor accelerates late stages of hair follicle morphogenesis, whereas brain-derived neurotrophic factor does not show significant effects. This suggests that the morphogenetic properties of locally generated neurotrophins in the skin, similar to their classical neurotrophic functions, are quite distinct and depend on the response patterns of the corresponding neurotrophin target receptor-expressing cells in the developing hair follicle. These data further strengthen the concept that neurotrophin signaling is an important element in controlling the rate of hair follicle morphogenesis, yet also highlight the complexity of this signaling system.
 
I found this in the thread linked below: (Thx Babcock)
http://www.longecity...timulating-ngf/

The thread is worth a read as t states that the extract from the mycelium or root of Loins Mane is far more powerful than that from the fruiting body and that Acetyl L Carnitine should increase the effect of NGF.

Maybe there is some truth in the old joke about rubbing chicken poop on your head!
Its sure to get fungi flourishing with its roots right in your scalp!




 

Edited by Logic, 03 July 2014 - 10:16 PM.

[Logic]

Ecklonia cava promotes hair growth.

http://www.ncbi.nlm....pubmed/24252083


Effect of Dieckol, a Component of Ecklonia cava, on the Promotion of Hair Growth.

http://www.ncbi.nlm....pubmed/22754373

Edited by Logic, 05 July 2014 - 08:34 PM.

[holdout]

how bout aromatherapy

 

good point! stress is a factor in hair loss. enter ashwagandha, rhodiola rosea, etc. etc.

 

 

from a nutritive perspective, you would want to supplement with ALL the B vitamins (so maybe take a B-100 complex pill), especially biotin, and, you can take a specialized formulation of actual keratin protein (the protein that's used to make hair, skin, and nails) together with zinc, to ensure that your hair follicles are dense/thick/strong and built to last!
 

[Logic]

All in all, it seems Niner doesn't base his recommendations on much actual knowledge. Considering the amount of research it took me to figure out even this much, I can understand why.

 
Can you point out where I made this alleged pin-headed recommendation?  As far as I can tell, the closest I ever came was saying that threonate was related to ascorbate (as opposed to, say, the amino acid threonine).  I don't think I ever said that ascorbate was a good source of threonate.

 
I had you and ScienceGuy mixed up Niner.  Soz

"...Personally, my recommendation if you are specifically seeking to supplement with L-THREONIC ACID / THREONATE is to take some ESTER-C; this comprises CALCIUM ASCORBATE-THREONATE, and provides high concentrations of both L-THREONATE as well as VITAMIN C in a highly bioactive form.

IMO this offers much better value for money than MAGNESIUM L-THREONATE ..."
 http://www.longecity...ndpost&p=587045

I am glad I found the post though as I would like to get ScienceGuy's input. It looks as though he is probably wrong about Ester-C?

[William Sterog]

What do you think about safflower oil in topic use?

[sensei]

C60 Olive oil -- Oral high dose intermittent and infrequent topical -- see pictures of my results

 

http://www.longecity...experiment-log/

Edited by sensei, 05 January 2015 - 05:51 PM.