haidut
Member
EDIT (11/1/2021): New version of Gonadin (called it Gonadin+ on one recent podcast with Danny Roddy, but I decided to keep the name as just Gonadin) has been released on November 1, 2021. The description of the ingredients that have been removed, and the studies about them, can be found in the archive thread below.
raypeatforum.com
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As I mentioned in a few threads before, I have always been interested in the so-called "reproductive aging", both in males and females. There is solid evidence that gonadal function declines with age and as such the synthesis and circulating levels of protective steroids like testosterone (T), progesterone (P4), DHEA, and pregnenolone (P5) declines in both men and women. Initially, this decline is buffered to a degree by increased adrenal activity and DHEA synthesis. But with advancing age, the adrenal layers that synthesis DHEA tend to atrophy, leaving cortisol and estrogen to rule unopposed.
Actually, total T levels in men do not decline with age but this appears to be due to decreased clearance, while de-novo synthesis in the Leydig cells does decline quite markedly with aging, in parallel to falling levels of pregnenolone, progesterone and DHEA. In women, after menopause progesterone, pregnenolone and DHEA levels decline just as sharply as they do in males.
raypeatforum.com
Interestingly, this decline in endogenous synthesis does not seem to be due to some kind of damage or atrophy of the gonads. To the contrary, cell extracted from "old" human gonads perform just as well as cells from "young" gonads when placed in optimal laboratory conditions with sufficient amount of precursors and enzyme co-factors. This shows that the decline in gonadal function is...well...functional and not structural. So, I have been searching for substances that can help restore such optimal endogenous environment to gonads. Thyroid hormone and high NAD/NADH ratio definitely seem to play a role, but there are additional pathways that appear to be involved and administering thyroid hormone is not always optimal or even desirable. One of the most extensively studied methods of restoring steroidogenesis in gonads (both female and male) is through inhibition of the enzyme aromatase (i.e. decrease estrogen synthesis). Aromatase inhibitors are now commonly used not only for breast and other endocrine cancers, but for treating so-called secondary hypogonadism - i.e. estrogen, which only rises with age, appears to be one of the primary blockers of proper gonadal function. Estrogen receptor antagonists are also commonly used for such purposes, which confirms the negative role estrogen has on proper gonadal function.
www.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
www.ncbi.nlm.nih.gov
In addition, other studies have demonstrated in both humans and animals that lowering prolactin and/or raising dopamine levels also has beneficial effects on gonadal function. It is now common to treat both male and female sexual dysfunction with dopamine agonists like bromocriptine, and the studies that also examined changes in steroid balance noticed normalization of gonadal function concurrent with the improvement in sexual function. This is not surprising as anti-prolactin/pro-dopamine chemicals tend to reduce estrogen synthesis and thus their overall effects are (functionally) similar to those or aromatase inhibitors. As a side note, it is not just dopamine agonists that have these beneficial effects on gonadal function, but any also any other intervention that results in increase in dopamine synthesis, decrease in its degradation (e.g. MAO-B inhibition), inhibition of its uptake, etc.
academic.oup.com
www.ncbi.nlm.nih.gov
onlinelibrary.wiley.com
Furthermore, more recent studies have discovered that elevated cortisol also plays a direct role in suppressing gonadal function, and that role is independent of, but synergistic with, estrogen. In addition, cortisol is well-known to promote aromatase activity, while estrogen promotes cortisol synthesis, resulting in a positive feedback loop (a vicious circle is a more appropriate term, IMO) that can wreak havoc on gonadal function. Conversely, lowering cortisol (and/or blocking its effects at the receptor level), may also help restore proper steroidogenesis, even in aged/stressed organisms.
onlinelibrary.wiley.com
www.ncbi.nlm.nih.gov
In summary, multiple studies demonstrate that anti-estrogen, anti-cortisol, and pro-dopamine pathways each have an independent beneficial effect on gonadal function and steroid balance. Also, a number of studies have suggested that a combination of these mechanisms may have synergistic effects stronger than each one on its own.
Given the mechanisms/parthways described above, we narrowed down the ingredient options to several substances. Namely, we selected α-naphthoflavone (ANF), also known as 7,8-benzoflavone (BZF), as the ingredient to address the aromatase inhibition. In addition, we selected flavanone to address the cortisol synthesis inhibition and MAO-B inhibition. Interestingly, there are studies showing flavanone also has aromatase inhibition effects, and that there is a synergistic effect in combining a flavone (e.g. apigenin) with a flavanone (e.g. naringenin). In the case of Gonadin the flavone is ANF/BZF, and the flavanone is..well...the (unsubstituted) flavanone
pubmed.ncbi.nlm.nih.gov
This synergy between a more saturated molecule (e.g. flavanone) and a less saturated molecule (e.g. ANF/BZF) is reminiscent to the synergy of combining a fully saturated steroid (e.g. androsterone) with a steroid that has one (1) double bond (e.g. DHEA), as per the thread below.
raypeatforum.com
In addition to the pathways/mechanisms discussed above, I have been researching the steroidal effects of various fatty acids and their esters. There is considerable evidence that saturated fats increase binding of androgens to their "receptors" and also increase androgen synthesis. Most of the studies on androgenic effects of saturated fat were done using the unmodified versions of such fats like palmitic and butyric acids. However, a recent study found that the methyl esters of some fatty acids have an even more potent androgenic effects and in even raise testosterone levels in castrated rats. While the effects of the fatty acid esters were not quite as potent as testosterone (T), the effects were not far behind those of dose of T administration. Also, the doses of fatty acid esters used was quite low and there is likely to be a dose-dependent effect, so higher doses would be more potent and may reach the effectiveness of T. Thus, using specific esters of fatty acids like palmitate and oleate may provide another non-steroid method of increasing gonadal activity and raising serum levels of androgens.
Androgenic effect of honeybee drone milk in castrated rats: roles of methyl palmitate and methyl oleate. - PubMed - NCBI
"..."...NMR and MS measurements after the second fractionation revealed MP and MO in the last active fraction (II/E) of the raw DM. Although MO alone had no effect on androgen-sensitive organs, MP (similarly to raw DM) increased the weights of the androgen sensitive organs (except the prostate) and these effects were flutamide-sensitive. Palmitate is known to play a role in steroidogenesis: it is able to increase the DHEA level through its CYP17 activity (Bellanger et al., 2012). A fatty acid infusion has been reported to elevate human androgen production in both sexes (Mai et al., 2006, 2008). MP was recently proved to inhibit carrageenan-induced paw oedema by reducing the prostaglandin E2 level (Saeed et al., 2012), an effect which might indicate a steroidogenesis-inducing property. Since DHEA alone has a weak androgenic effect, the putative DHEA-elevating effect of MP may explain in part the response of androgen-sensitive organs. The androgenic dose (25 μg/kg) of MP alone did not alter the plasma testosterone level, but its combination with MO in high dose exhibited plasma testosterone-increasing effect, similarly to the action of raw DM. It is known that oleic acid has a weak 5-α- reductase inhibitory effect, preventing testosterone conversion to dihydrotestosterone, whereas the esterified analogues of oleic acid (like MO) are ineffective in this respect (Liu et al., 2009). As yet we have no explanation as to why the combination of MP and MO increases the plasma testosterone level in rat. Nevertheless, we have clearly shown that these two compounds have a major role in the main androgenic action of DM. Further studies are required to clarify the androgenic mechanisms of action of MO and MP.""
Interestingly, it is worth noting that when the palmitate ester (an SFA) was used on its own it only had androgenic effects. However, combined with an oleate ester (a MUFA) it also raised T levels in the castrated rats. This synergistic effect of saturated and mildly unsaturated substances has been seen in many other studies with steroids where the effects of combining a saturated steroids like androsterone are much more potent when it is combined with an unsaturated steroid like DHEA. The same effects have been seen with combinations of T/DHT and DHT/DHEA. So, I doubt the findings of this study are a coincidence, and this is what led me to add both the palmitate and oleate esters to the product.
In addition to methyl palmitate and methyl oleate, another SFA which has been found to have an androgenic effect is caprylic acid. I have posted other studies about caprylic (octanoic) acid in regards to its anti-cancer effects and anti-cortisol effects, which would be quite expected if it is indeed androgenic.
Novel phytoandrogens and lipidic augmenters from Eucommia ulmoides
"...Subsequent 1H NMR and GC analyses of active fraction CB showed the major presence of the 8-carbon polysaturated fatty acid, caprylic acid, along with other lipids (figure (figure1313 and table table1).1). Bioassays using pure caprylic acid and other polysaturated fatty acids (PFAs) correlated with the augmenting effect of E. ulmoides on the AR (figure (figure14)14) in varying degrees. Ethanolic extract of coconut (Cocos nucifera) flesh, rich in C-8 caprylic acid and other polysaturated fatty acids [11], replicated the hormone potentiating effect of both E. ulmoides extract and pure caprylic acid in AR bioassays (data not shown)."
Thus, in light of the published evidence for flavanone, ANF/BZF, and the fatty acid esters I decided to release the product Gonadin. Its primary purpose is endogenous steroid optimization, however, it may be able to do more than that judging from the studies in the "References" section below.
*******************************************************************************
Gonadin is a liquid product for optimizing endogenous steroid synthesis. Its ingredients have been studied for aromatase inhbition (ANF/BZF, flavanone), cortisol synthesis inhibition (flavanone), MAO-B inhibition (flavanone), increasing androgen synthesis (methyl palmitate and methyl oleate), and increasing androgen receptor (AR) expression (caprylic acid). Based on the mechanisms described above and the studies referenced below, the combination of the four (4) ingredients (plus caprylic acid, present as one of the solvents) may help optimize the endogenous steroid balance.
Units per container: about 30
Unit size: 8 drops
Each unit contains the following ingredients:
Flavanone: 32mg
α-Naphthoflavone: 16mg
Methyl palmitate: 3.3mg
Methyl oleate: 3.3mg
Other ingredients: add product to shopping cart to see info
*******************************************************************************
References:
1. Inhibition of cortisol synthesis by flavanone and ANF.
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
"...Plasma cortisol levels were significantly higher with BNF in the present study and this BNF-mediated cortisol response was completely abolished with ANF suggesting a role for AhR and/or CYP1A in the regulation of plasma cortisol concentration. "
2. Aromatase inhibition (IC50: 5μM - 8μM) by flavanone.
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
www.sciencedirect.com
3. Selective inhibition of MAO-B by flavanone.
pubmed.ncbi.nlm.nih.gov
4. Aromatase inhibition (IC50: 0.070μM - 1.3μM) and/or pro-gonadal effects of ANF/BZF .
pubmed.ncbi.nlm.nih.gov
"...Alpha-Naphthoflavone (7,8-benzoflavone), a synthetic flavonoid, is a potent inhibitor of aromatase with an I50 value of 0.5 μM..."
pubmed.ncbi.nlm.nih.gov
"...At necropsy, breast tumor incidence in the E(2), E(2) + vitamin C and E(2) + ANF groups was 82, 29 and 0%, respectively. Vitamin C and ANF attenuated E(2)-induced alterations in oxidative stress markers in breast tissue, including 8-iso-prostane F(2alpha) formation and changes in the activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase. Quantification of 2-hydroxyestradiol (2-OHE(2)) and 4-hydroxyestradiol (4-OHE(2)) formation in breast tissue confirmed that ANF inhibited 4-hydroxylation of E(2) and decreased formation of the highly carcinogenic 4-OHE(2). These results demonstrate that antioxidant vitamin C reduces the incidence of estrogen-induced mammary tumors, increases tumor latency and decreases oxidative stress in vivo. Further, our data indicate that ANF completely abrogates breast cancer development in ACI rats. The present study is the first to demonstrate the inhibition of breast carcinogenesis by antioxidant vitamin C or the estrogen metabolic inhibitor ANF in an animal model of estrogen-induced mammary carcinogenesis. Taken together, these results suggest that E(2) metabolism and oxidant stress are critically involved in estrogen-induced breast carcinogenesis."
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
www.sciencedirect.com
www.sciencedirect.com
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
5. Miscellaneous
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
Archive info for old Gonadin version
This thread is just a placeholder for the information about the ingredients in the previous version of Gonadin that we had. The new version replaced 2 of the ingredients - phytol and squalene - with flavanone and alpha-naphthoflavone. The methylated fatty acids are still there. The text below is...
As I mentioned in a few threads before, I have always been interested in the so-called "reproductive aging", both in males and females. There is solid evidence that gonadal function declines with age and as such the synthesis and circulating levels of protective steroids like testosterone (T), progesterone (P4), DHEA, and pregnenolone (P5) declines in both men and women. Initially, this decline is buffered to a degree by increased adrenal activity and DHEA synthesis. But with advancing age, the adrenal layers that synthesis DHEA tend to atrophy, leaving cortisol and estrogen to rule unopposed.
Actually, total T levels in men do not decline with age but this appears to be due to decreased clearance, while de-novo synthesis in the Leydig cells does decline quite markedly with aging, in parallel to falling levels of pregnenolone, progesterone and DHEA. In women, after menopause progesterone, pregnenolone and DHEA levels decline just as sharply as they do in males.
Pregnenolone, Progesterone And DHEA Drop, Cortisol Rises In Aging
I posted a few times about the steroidal characteristics of aging. Many people think there is a drop in testosterone (T) in aging and that is what drives the frailty of aging both in men and women. However, numerous studies show that that total T does not decrease with aging. What does seem to...
Interestingly, this decline in endogenous synthesis does not seem to be due to some kind of damage or atrophy of the gonads. To the contrary, cell extracted from "old" human gonads perform just as well as cells from "young" gonads when placed in optimal laboratory conditions with sufficient amount of precursors and enzyme co-factors. This shows that the decline in gonadal function is...well...functional and not structural. So, I have been searching for substances that can help restore such optimal endogenous environment to gonads. Thyroid hormone and high NAD/NADH ratio definitely seem to play a role, but there are additional pathways that appear to be involved and administering thyroid hormone is not always optimal or even desirable. One of the most extensively studied methods of restoring steroidogenesis in gonads (both female and male) is through inhibition of the enzyme aromatase (i.e. decrease estrogen synthesis). Aromatase inhibitors are now commonly used not only for breast and other endocrine cancers, but for treating so-called secondary hypogonadism - i.e. estrogen, which only rises with age, appears to be one of the primary blockers of proper gonadal function. Estrogen receptor antagonists are also commonly used for such purposes, which confirms the negative role estrogen has on proper gonadal function.
Aromatase inhibitors in men: effects and therapeutic options
Aromatase inhibitors effectively delay epiphysial maturation in boys and improve testosterone levels in adult men Therefore, aromatase inhibitors may be used to increase adult height in boys with gonadotropin-independent precocious puberty, idiopathic ...
www.ncbi.nlm.nih.gov
Clomiphene Citrate for the Treatment of Hypogonadism - PubMed
CC is safe and effective and should remain in the armament of urologists treating hypogonadal men, especially men interested in preservation of fertility. Wheeler KM, Sharma D, Kavoussi PK, et al. Clomiphene citrate for the treatment of hypogonadism. Sex Med Rev 2019;7:272-276.
pubmed.ncbi.nlm.nih.gov
Complete reversal of adult-onset isolated hypogonadotropic hypogonadism with clomiphene citrate - PubMed
Isolated hypogonadotropic hypogonadism may result from an acquired defect of enhanced hypothalamic sensitivity to E-mediated negative feedback. Whereas direct T replacement therapy can further suppress endogenous gonadotropin secretion, treating IHH men with gonadotropins can stimulate...
pubmed.ncbi.nlm.nih.gov
CLOMIPHENE CITRATE IN THE TREATMENT OF IDIOPATHIC OR FUNCTIONAL HYPOGONADOTROPIC HYPOGONADISM IN MEN: A CASE SERIES AND REVIEW OF THE LITERATURE - PubMed
FSH = follicle-stimulating hormone LH = luteinizing hormone LOH = late-onset hypogonadotropic hypogonadism.
pubmed.ncbi.nlm.nih.gov
Treatment of Men with Central Hypogonadism: Alternatives for Testosterone Replacement Therapy - PubMed
Central hypogonadism is a clinical condition, characterized by sexual symptoms and low serum testosterone levels, due to an impaired function of the hypothalamus or pituitary gland. Testosterone replacement therapy (TRT) is the standard treatment for hypogonadism, but it has some disadvantages...
pubmed.ncbi.nlm.nih.gov
The Role of Estrogen Modulators in Male Hypogonadism and Infertility
Estradiol, normally considered a female hormone, appears to play a significant role in men in a variety of physiologic functions, such as bone metabolism, cardiovascular health, and testicular function. As such, estradiol has been targeted by male reproductive ...
www.ncbi.nlm.nih.gov
In addition, other studies have demonstrated in both humans and animals that lowering prolactin and/or raising dopamine levels also has beneficial effects on gonadal function. It is now common to treat both male and female sexual dysfunction with dopamine agonists like bromocriptine, and the studies that also examined changes in steroid balance noticed normalization of gonadal function concurrent with the improvement in sexual function. This is not surprising as anti-prolactin/pro-dopamine chemicals tend to reduce estrogen synthesis and thus their overall effects are (functionally) similar to those or aromatase inhibitors. As a side note, it is not just dopamine agonists that have these beneficial effects on gonadal function, but any also any other intervention that results in increase in dopamine synthesis, decrease in its degradation (e.g. MAO-B inhibition), inhibition of its uptake, etc.
Six Months of Treatment with Cabergoline Restores Sexual Potency in Hyperprolactinemic Males: An Open Longitudinal Study Monitoring Nocturnal Penile Tumescence
This open longitudinal study investigated the prevalence of depressed sexual potency by monitoring erectile dysfunction using nocturnal penile tumescence (
academic.oup.com
Effects on Sperms’ Quality of Selegiline in Aged Rats
Selegiline is used to treat Parkinsonian patients. Other indications of its use have recently been discovered.Scouting special and beneficial side effects of selegiline treatment.Two-year old male Wistar rats were daily treated with 0.25 mg/kg of selegiline ...
www.ncbi.nlm.nih.gov
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Furthermore, more recent studies have discovered that elevated cortisol also plays a direct role in suppressing gonadal function, and that role is independent of, but synergistic with, estrogen. In addition, cortisol is well-known to promote aromatase activity, while estrogen promotes cortisol synthesis, resulting in a positive feedback loop (a vicious circle is a more appropriate term, IMO) that can wreak havoc on gonadal function. Conversely, lowering cortisol (and/or blocking its effects at the receptor level), may also help restore proper steroidogenesis, even in aged/stressed organisms.
Error - Cookies Turned Off
Effect of exogenous glucocorticoids on male hypogonadism
The aim of the present study was to investigate the effects of exogenous glucocorticoids (GCs), a potent cause of male hypogonadism, on the function of the hypothalamic-pituitary-gonadal axis, and to determine their secondary effects in male patients. ...
www.ncbi.nlm.nih.gov
CN102091060A - Drug for treating or preventing hypogonadism, sexual dysfunction and/or sterility mediated by glucocorticoid and application thereof - Google Patents
The invention relates to application of the following 13 compounds such as a compound LG13 and the like in preparing a drug for preventing or treating diseases such as hypogonadism. The 13 compounds can treat or prevent the hypogonadism, sexual dysfunction and/or sterility which are mediated by...
patents.google.com
In summary, multiple studies demonstrate that anti-estrogen, anti-cortisol, and pro-dopamine pathways each have an independent beneficial effect on gonadal function and steroid balance. Also, a number of studies have suggested that a combination of these mechanisms may have synergistic effects stronger than each one on its own.
Given the mechanisms/parthways described above, we narrowed down the ingredient options to several substances. Namely, we selected α-naphthoflavone (ANF), also known as 7,8-benzoflavone (BZF), as the ingredient to address the aromatase inhibition. In addition, we selected flavanone to address the cortisol synthesis inhibition and MAO-B inhibition. Interestingly, there are studies showing flavanone also has aromatase inhibition effects, and that there is a synergistic effect in combining a flavone (e.g. apigenin) with a flavanone (e.g. naringenin). In the case of Gonadin the flavone is ANF/BZF, and the flavanone is..well...the (unsubstituted) flavanone
Enhanced action of apigenin and naringenin combination on estrogen receptor activation in non-malignant colonocytes: implications on sorghum-derived phytoestrogens - PubMed
Activation of estrogen receptor-β (ERβ) is an important mechanism for colon cancer prevention. Specific sorghum varieties that contain flavones were shown to activate ER in non-malignant colonocytes at low concentrations. This study aimed to determine positive interactions among estrogenic...
pubmed.ncbi.nlm.nih.gov
This synergy between a more saturated molecule (e.g. flavanone) and a less saturated molecule (e.g. ANF/BZF) is reminiscent to the synergy of combining a fully saturated steroid (e.g. androsterone) with a steroid that has one (1) double bond (e.g. DHEA), as per the thread below.
Remarkable Synergistic Effect Of Androsterone With DHEA
The steroids androsterone (A) and DHEA are considered not very strong androgens in terms of direct activity on androgenic receptors. DHEA is often cited as having 1/10 of the androgenic effects of testosterone (T) and androsterone as having 1/7 of the androgenic effects. While that has been...
In addition to the pathways/mechanisms discussed above, I have been researching the steroidal effects of various fatty acids and their esters. There is considerable evidence that saturated fats increase binding of androgens to their "receptors" and also increase androgen synthesis. Most of the studies on androgenic effects of saturated fat were done using the unmodified versions of such fats like palmitic and butyric acids. However, a recent study found that the methyl esters of some fatty acids have an even more potent androgenic effects and in even raise testosterone levels in castrated rats. While the effects of the fatty acid esters were not quite as potent as testosterone (T), the effects were not far behind those of dose of T administration. Also, the doses of fatty acid esters used was quite low and there is likely to be a dose-dependent effect, so higher doses would be more potent and may reach the effectiveness of T. Thus, using specific esters of fatty acids like palmitate and oleate may provide another non-steroid method of increasing gonadal activity and raising serum levels of androgens.
Androgenic effect of honeybee drone milk in castrated rats: roles of methyl palmitate and methyl oleate. - PubMed - NCBI
"..."...NMR and MS measurements after the second fractionation revealed MP and MO in the last active fraction (II/E) of the raw DM. Although MO alone had no effect on androgen-sensitive organs, MP (similarly to raw DM) increased the weights of the androgen sensitive organs (except the prostate) and these effects were flutamide-sensitive. Palmitate is known to play a role in steroidogenesis: it is able to increase the DHEA level through its CYP17 activity (Bellanger et al., 2012). A fatty acid infusion has been reported to elevate human androgen production in both sexes (Mai et al., 2006, 2008). MP was recently proved to inhibit carrageenan-induced paw oedema by reducing the prostaglandin E2 level (Saeed et al., 2012), an effect which might indicate a steroidogenesis-inducing property. Since DHEA alone has a weak androgenic effect, the putative DHEA-elevating effect of MP may explain in part the response of androgen-sensitive organs. The androgenic dose (25 μg/kg) of MP alone did not alter the plasma testosterone level, but its combination with MO in high dose exhibited plasma testosterone-increasing effect, similarly to the action of raw DM. It is known that oleic acid has a weak 5-α- reductase inhibitory effect, preventing testosterone conversion to dihydrotestosterone, whereas the esterified analogues of oleic acid (like MO) are ineffective in this respect (Liu et al., 2009). As yet we have no explanation as to why the combination of MP and MO increases the plasma testosterone level in rat. Nevertheless, we have clearly shown that these two compounds have a major role in the main androgenic action of DM. Further studies are required to clarify the androgenic mechanisms of action of MO and MP.""
Interestingly, it is worth noting that when the palmitate ester (an SFA) was used on its own it only had androgenic effects. However, combined with an oleate ester (a MUFA) it also raised T levels in the castrated rats. This synergistic effect of saturated and mildly unsaturated substances has been seen in many other studies with steroids where the effects of combining a saturated steroids like androsterone are much more potent when it is combined with an unsaturated steroid like DHEA. The same effects have been seen with combinations of T/DHT and DHT/DHEA. So, I doubt the findings of this study are a coincidence, and this is what led me to add both the palmitate and oleate esters to the product.
In addition to methyl palmitate and methyl oleate, another SFA which has been found to have an androgenic effect is caprylic acid. I have posted other studies about caprylic (octanoic) acid in regards to its anti-cancer effects and anti-cortisol effects, which would be quite expected if it is indeed androgenic.
Novel phytoandrogens and lipidic augmenters from Eucommia ulmoides
"...Subsequent 1H NMR and GC analyses of active fraction CB showed the major presence of the 8-carbon polysaturated fatty acid, caprylic acid, along with other lipids (figure (figure1313 and table table1).1). Bioassays using pure caprylic acid and other polysaturated fatty acids (PFAs) correlated with the augmenting effect of E. ulmoides on the AR (figure (figure14)14) in varying degrees. Ethanolic extract of coconut (Cocos nucifera) flesh, rich in C-8 caprylic acid and other polysaturated fatty acids [11], replicated the hormone potentiating effect of both E. ulmoides extract and pure caprylic acid in AR bioassays (data not shown)."
Thus, in light of the published evidence for flavanone, ANF/BZF, and the fatty acid esters I decided to release the product Gonadin. Its primary purpose is endogenous steroid optimization, however, it may be able to do more than that judging from the studies in the "References" section below.
*******************************************************************************
Gonadin is a liquid product for optimizing endogenous steroid synthesis. Its ingredients have been studied for aromatase inhbition (ANF/BZF, flavanone), cortisol synthesis inhibition (flavanone), MAO-B inhibition (flavanone), increasing androgen synthesis (methyl palmitate and methyl oleate), and increasing androgen receptor (AR) expression (caprylic acid). Based on the mechanisms described above and the studies referenced below, the combination of the four (4) ingredients (plus caprylic acid, present as one of the solvents) may help optimize the endogenous steroid balance.
Units per container: about 30
Unit size: 8 drops
Each unit contains the following ingredients:
Flavanone: 32mg
α-Naphthoflavone: 16mg
Methyl palmitate: 3.3mg
Methyl oleate: 3.3mg
Other ingredients: add product to shopping cart to see info
*******************************************************************************
References:
1. Inhibition of cortisol synthesis by flavanone and ANF.
A rapid screening assay for inhibitors of 11beta-hydroxysteroid dehydrogenases (11beta-HSD): flavanone selectively inhibits 11beta-HSD1 reductase activity - PubMed
A rapid screening assay for chemicals inhibiting 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 or type 2 using lysates from stably transfected cells was developed. Here, we tested a series of environmental chemicals for anti-11beta-HSD activities. Inhibition of 11beta-HSD2, which may...
pubmed.ncbi.nlm.nih.gov
Comparative enzymology of 11beta-hydroxysteroid dehydrogenase type 1 from six species - PubMed
11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1), catalyzing the intracellular activation of cortisone to cortisol, is currently considered a promising target to treat patients with metabolic syndrome; hence, there is considerable interest in the development of selective inhibitors. For...
pubmed.ncbi.nlm.nih.gov
beta-Naphthoflavone disrupts cortisol production and liver glucocorticoid responsiveness in rainbow trout - PubMed
We investigated the impact of aryl hydrocarbon receptor (AhR) activation on cortisol production in rainbow trout (Oncorhynchus mykiss) using beta-naphthoflavone (BNF) and alpha-naphthoflavone (ANF) as agonist and antagonist of AhR, respectively. Fish were given a single intraperitoneal injection...
pubmed.ncbi.nlm.nih.gov
2. Aromatase inhibition (IC50: 5μM - 8μM) by flavanone.
Inhibition of human estrogen synthetase (aromatase) by flavones - PubMed
Several naturally occurring and synthetic flavones were found to inhibit the aromatization of androstenedione and testosterone to estrogens catalyzed by human placental and ovarian microsomes. These flavones include (in order of decreasing potency) 7,8-benzoflavone, chrysin, apigenin, flavone...
pubmed.ncbi.nlm.nih.gov
Inhibition of aromatase activity by flavonoids - PubMed
In searching for potent cancer chemopreventive agents from synthetic or natural products, 28 randomly selected flavonoids were screened for inhibitory effects against partially purified aromatase prepared from human placenta. Over 50% of the flavonoids significantly inhibited aromatase activity...
pubmed.ncbi.nlm.nih.gov
Aromatase inhibition by flavonoids - PubMed
Several synthetic flavones were found to inhibit the aromatization of androstenedione to estrone catalyzed by human placental microsomes. Twenty-one compounds were tested and the IC50 of the most active were: flavone, 10 microM; 7-hydroxyflavone, 0.5 microM; 7,4'-dihydroxyflavone, 2.0 microM...
pubmed.ncbi.nlm.nih.gov
Molecular modeling evaluation of non-steroidal aromatase inhibitors - PubMed
A recent discovery of aromatase crystal structure triggered the efforts to design novel aromatase inhibitors for breast cancer therapy. While correlating docking scores with inhibitory potencies of known ligands, feeble robustness of scoring functions toward prediction was observed. This...
pubmed.ncbi.nlm.nih.gov
Inhibitory effect of chrysin on estrogen biosynthesis by suppression of enzyme aromatase (CYP19): A systematic review
The cytochrome P450 enzyme functions as the rate-limiting enzyme in changing androgens to estrogens. Inhibition of aromatase is one of the significant…
3. Selective inhibition of MAO-B by flavanone.
A new series of flavones, thioflavones, and flavanones as selective monoamine oxidase-B inhibitors - PubMed
A new series of synthetic flavones, thioflavones, and flavanones has been synthesized and evaluated as potential inhibitors of monoamine oxidase isoforms (MAO-A and -B). The most active series is the flavanone one with higher selective inhibitory activity against MAO-B. Some of these flavanones...
pubmed.ncbi.nlm.nih.gov
4. Aromatase inhibition (IC50: 0.070μM - 1.3μM) and/or pro-gonadal effects of ANF/BZF .
Beneficial effects of chrysin and benzoflavone on virility in 2-year-old male rats - PubMed
This work describes the potential usefulness of bioflavonoids for countering the deleterious effects of aging on male sexuality in 2-year-old rats. A flavone chrysin from Passiflora caerulea Linn. and a benzoflavone moiety (BZF) recently isolated from Passiflora incarnata Linn. were administered...
pubmed.ncbi.nlm.nih.gov
alpha-Naphthoflavone | ≥99%(HPLC) | Selleck | Aromatase inhibitor
Alpha-Naphthoflavone (7,8-benzoflavone), a synthetic flavonoid, is a potent inhibitor of aromatase with an I50 value of 0.5 μM. Quality confirmed by NMR & HPLC. See customer reviews, validations & product citations.
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Vitamin C and alpha-naphthoflavone prevent estrogen-induced mammary tumors and decrease oxidative stress in female ACI rats - PubMed
The mechanisms underlying the pathogenesis of estrogen-induced breast carcinogenesis remain unclear. The present study investigated the roles of estrogen metabolism and oxidative stress in estrogen-mediated mammary carcinogenesis in vivo. Female August Copenhagen Irish (ACI) rats were treated...
pubmed.ncbi.nlm.nih.gov
New 7,8-benzoflavanones as potent aromatase inhibitors: synthesis and biological evaluation - PubMed
Some natural compounds such as flavonoids are known to possess a moderate inhibitory activity against aromatase, this enzyme being an interesting target for hormone-dependent breast cancer treatment. It has been demonstrated that the modulation of flavonoid skeleton could increase anti-aromatase...
pubmed.ncbi.nlm.nih.gov
Inhibition of human estrogen synthetase (aromatase) by flavones - PubMed
Several naturally occurring and synthetic flavones were found to inhibit the aromatization of androstenedione and testosterone to estrogens catalyzed by human placental and ovarian microsomes. These flavones include (in order of decreasing potency) 7,8-benzoflavone, chrysin, apigenin, flavone...
pubmed.ncbi.nlm.nih.gov
Flavonoid inhibition of aromatase enzyme activity in human preadipocytes - PubMed
Eleven flavonoid compounds were compared with aminoglutethimide (AG), a pharmaceutical aromatase inhibitor, for their abilities to inhibit aromatase enzyme activity in a human preadipocyte cell culture system. Flavonoids exerting no effect on aromatase activity were catechin, daidzein, equol...
pubmed.ncbi.nlm.nih.gov
Inhibition of aromatase cytochrome P-450 (estrogen synthetase) by derivatives of alpha-naphthoflavone - PubMed
alpha-Naphthoflavone (ANF; 7,8-benzoflavone) is a potent competitive inhibitor of human aromatase cytochrome P-450 [J. T. Kellis, Jr. and L. E. Vickery, Science 225, 1032 (1984)]. We have further investigated inhibition of aromatase by several derivatives of ANF. Using human placental microsomes...
pubmed.ncbi.nlm.nih.gov
Effects of flavonoids on aromatase activity, an in vitro study - PubMed
In the study, the inhibitory effect of flavonoids, including isoflavonic phytoestrogens, on the ovarian aromatase enzyme complex from the rainbow trout, Oncorhynchus mykiss, was assessed in vitro. Some of the compounds tested on fish were also tested on human placental aromatase activity as a...
pubmed.ncbi.nlm.nih.gov
Induction and inhibition of aromatase (CYP19) activity by natural and synthetic flavonoid compounds in H295R human adrenocortical carcinoma cells - PubMed
Flavonoids and related structures (e.g., flavones, isoflavones, flavanones, catechins) exert various biological effects, including anticarcinogenic, antioxidant and (anti-)estrogenic effects, and modulation of sex hormone homeostasis. A key enzyme in the synthesis of estrogens from androgens is...
pubmed.ncbi.nlm.nih.gov
Inhibitory effect of chrysin on estrogen biosynthesis by suppression of enzyme aromatase (CYP19): A systematic review
The cytochrome P450 enzyme functions as the rate-limiting enzyme in changing androgens to estrogens. Inhibition of aromatase is one of the significant…
Inhibitory effect of chrysin on estrogen biosynthesis by suppression of enzyme aromatase (CYP19): A systematic review
The cytochrome P450 enzyme functions as the rate-limiting enzyme in changing androgens to estrogens. Inhibition of aromatase is one of the significant…
Aphrodisiac activity of methanol extract of leaves of Passiflora incarnata Linn in mice - PubMed
The aphrodisiac properties of the methanol extract of leaves of Passiflora incarnata Linn. have been evaluated in mice by observing the mounting behaviour. The methanol extract of P. incarnata exhibited significant aphrodisiac behaviour in male mice at all doses, i.e. 75, 100 and 150 mg/kg...
pubmed.ncbi.nlm.nih.gov
Prevention of chronic alcohol and nicotine-induced azospermia, sterility and decreased libido, by a novel tri-substituted benzoflavone moiety from Passiflora incarnata Linneaus in healthy male rats - PubMed
Excessive long term consumption of alcohol and nicotine have serious detrimental effects upon the libido, fertility, and sperm count in male species. The present work describes the beneficial effects of a novel tri-substituted benzoflavone moiety (BZF) isolated from Passiflora incarnata...
pubmed.ncbi.nlm.nih.gov
Restoration of chronic-Delta 9-THC-induced decline in sexuality in male rats by a novel benzoflavone moiety from Passiflora incarnata Linn - PubMed
1 The present study comprised treatment of healthy male rats with Delta(9)-tetrahydrocannabinol (THC, 10 mg kg(-1), p.o.), and combinations of THC with benzoflavone moiety (BZF, 10 and 20 mg kg(-1), p.o.) isolated from Passiflora incarnata Linneaus, over a period of 30 days. 2 Upon 30-days...
pubmed.ncbi.nlm.nih.gov
5. Miscellaneous
The tumor-growth inhibitory activity of flavanone and 2'-OH flavanone in vitro and in vivo through induction of cell cycle arrest and suppression of cyclins and CDKs - PubMed
Natural products, including flavonoids, are suggested to be involved in the protective effects of fruits and vegetables against cancer. However, studies concerning the effect of flavonoids frequently lacked data regarding to flavanones. In this study, we investigated the inhibitory effect of...
pubmed.ncbi.nlm.nih.gov
Improvement of Testicular Steroidogenesis Using Flavonoids and Isoflavonoids for Prevention of Late-Onset Male Hypogonadism - PubMed
Androgen production, being important for male fertility, is mainly accomplished by the Leydig cells from the interstitial compartment of the testis. Testosterone plays a critical role in testis development, normal masculinization, and the maintenance of spermatogenesis. Within seminiferous...
pubmed.ncbi.nlm.nih.gov
Attenuation of benzodiazepine dependence in mice by a tri-substituted benzoflavone moiety of Passiflora incarnata Linneaus: a non-habit forming anxiolytic - PubMed
The studies revealed that the chronic administration of the BZF moiety (three doses), did not exhibit any dependence-liability of its own, even upon an abrupt cessation. Additionally, the BZF co-treatments with diazepam also prevented the incurrence of diazepam-dependence, which might be because...
pubmed.ncbi.nlm.nih.gov
Correct Identification of Passiflora incarnata Linn., a Promising Herbal Anxiolytic and Sedative - PubMed
Passiflora incarnata Linn. and Passiflora edulis Sims are the two important plants of the family Passifloraceae that have often been reported as synonymous because of their identical morphological and microscopic characteristics. P. incarnata is a popular sedative and anxiolytic, whereas, P...
pubmed.ncbi.nlm.nih.gov
Anti-anxiety studies on extracts of Passiflora incarnata Linneaus - PubMed
Passiflora incarnata Linn. has been used to cure anxiety and insomnia since time immemorial. Despite the worldwide use of P. incarnata, the pharmacological work on this plant had been inadequate, inconclusive and wage as the earlier reports were unable to infer the mode of action of the plant as...
pubmed.ncbi.nlm.nih.gov
Drug/substance reversal effects of a novel tri-substituted benzoflavone moiety (BZF) isolated from Passiflora incarnata Linn.--a brief perspective - PubMed
The present work is a mini-review of the author's original work on the plant Passiflora incarnata Linn., which is used in several parts of the world as a traditional medicine for the management of anxiety, insomnia, epilepsy and morphine addiction. A tri-substituted benzoflavone moiety (BZF) has...
pubmed.ncbi.nlm.nih.gov
Reversal of cannabinoids (delta9-THC) by the benzoflavone moiety from methanol extract of Passiflora incarnata Linneaus in mice: a possible therapy for cannabinoid addiction - PubMed
The newly reported benzoflavone moiety from the plant Passiflora incarnata Linneaus has been evaluated in light of traditional reports on the use of P. incarnata in breaking down cannabis addiction. In the modern or allopathic system of therapeutics, there has been no suitable remedy to combat...
pubmed.ncbi.nlm.nih.gov
Nicotine reversal effects of the benzoflavone moiety from Passiflora incarnata Linneaus in mice - PubMed
A benzoflavone moiety (BZF) has recently been reported to be liable for many of the biological effects of the plant Passiflora incarnata Linneaus. In light of various reports mentioning the usefulness of P. incarnata in tobacco addiction, studies have been performed using four doses (1, 5, 10...
pubmed.ncbi.nlm.nih.gov
Antiasthmatic activity of the methanol extract of leaves of Passiflora incarnata - PubMed
The methanol extract of the leaves of P. incarnata was evaluated for its antiasthmatic effects against acetylcholine chloride (Ach)-induced-bronchospasm in guinea-pigs at doses of 50, 100 and 200 mg/kg. Using a 7-day treatment regimen, significant prevention of dyspnoea-related-convulsions was...
pubmed.ncbi.nlm.nih.gov
Suppression of alcohol-cessation-oriented hyper-anxiety by the benzoflavone moiety of Passiflora incarnata Linneaus in mice - PubMed
A benzoflavone moiety has been reported recently to be responsible for the multifarious CNS effects of Passiflora incarnata Linneaus. In the light of the established usefulness of the benzoflavone moiety in counteracting the withdrawal effects of substances like morphine, cannabinoids and...
pubmed.ncbi.nlm.nih.gov
Benzoflavone derivatives as potent antihyperuricemic agents - PubMed
Two series of benzoflavone derivatives were rationally designed, synthesized and evaluated for their xanthine oxidase (XO) inhibitory potential. Among both series, eight compounds (<b>NF-2</b>, <b>NF-4</b>, <b>NF-9</b>, <b>NF-12</b>, <b>NF-16</b>, <b>NF-25</b>, <b>NF-28</b>, and <b>NF-32</b>)...
pubmed.ncbi.nlm.nih.gov
Inhibitory effect of 7,8-benzoflavone on DMBA- and BaP-induced bone marrow micronuclei in mouse - PubMed
Frequencies of micronucleated polychromatic erythrocytes (PCE) were analyzed in bone-marrow cells of mice injected with 7,12-dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene (BaP), 7,8-benzoflavone (alpha-naphthoflavone) and the combination of either 7,8-benzoflavone and DMBA or 7,8-benzoflavone...
pubmed.ncbi.nlm.nih.gov
7,8-Benzoflavone: an inhibitor of prostaglandin synthesis and ornithine decarboxylase in murine epidermal cultures - PubMed
7,8-Benzoflavone (7,8-BF), over a dose range of 0.1-10 microM, partially inhibited the synthesis of prostaglandin E2 (PGE2) in primary cultures of epidermal cells from SENCAR mice, and completely suppressed the TPA-dependent stimulation of PGE2 synthesis. Under identical conditions 7,8-BF also...
pubmed.ncbi.nlm.nih.gov
Mechanism of cytochrome P450 activation by caffeine and 7,8-benzoflavone in rat liver microsomes - PubMed
Caffeine and 7,8-benzoflavone activate CYP3A2 in rat liver microsomes. Both activators appear to enhance enzyme activity by an increase in Vmax and to a lesser extent a decrease in Km. Additive effect studies demonstrated that the two activators oppose one another's effect. Electron transfer...
pubmed.ncbi.nlm.nih.gov
Flavonoids chrysin and benzoflavone, potent breast cancer resistance protein inhibitors, have no significant effect on topotecan pharmacokinetics in rats or mdr1a/1b (-/-) mice - PubMed
Breast cancer resistance protein (BCRP) is a recently identified ATP-binding cassette transporter, important in drug disposition and in the development of multidrug resistance in cancer. Flavonoids, a major class of natural compounds widely present in foods and herbal products, have been shown...
pubmed.ncbi.nlm.nih.gov
[Effect of 7,8-benzoflavone on the incidence of skin tumors induced by polycyclic hydrocarbons] - PubMed
Tumours were induced in CBA mice or (C57BL X CBA)F1 hybrids by the application of benz(a)pyrene (BP), 6-methylBP, 6-formylBP or 7,12-dimethylbenzanthracene (DMBA) to the skin. 7,8-benzoflavone (BF) used in combination with the mentioned agents decreased the carcinogenic action of...
pubmed.ncbi.nlm.nih.gov
Differential effects of 7,8-benzoflavone on polycyclic aromatic hydrocarbon dependent mutagenesis and cytotoxicity in a keratinocyte cell-mediated mutation assay - PubMed
A murine keratinocyte cell-mediated mutagenesis assay was used to examine the effects of 7,8-benzoflavone (7,8-BF) on the metabolic activation of 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (BP) to mutagenic and cytotoxic metabolites. DMBA-dependent mutagenesis and cytotoxicity were...
pubmed.ncbi.nlm.nih.gov
Inhibition of the prenatal dimethylbenz[a]anthracene-induced tumour initiation in mice by prior administration of 7,8-benzoflavone - PubMed
7,8-Benzoflavone (BF) was applied orally via stomach tube in doses of 50, 100, 200 and 400 mg/kg body weight to pregnant NMRI mice on the 18th day of gestation. BF application was followed 1 h later by oral administration of 60 mg/kg body weight dimethylbenz[a]anthracene (DMBA). As a rule this...
pubmed.ncbi.nlm.nih.gov
Effects of 7, 8-benzoflavone and SKF 525-A on the enzyme-mediated mutagenicity of phenylenediamines - PubMed
The effects of microsomal enzyme inhibitors (7, 8-BF and SKF 525-A) on the S-9-mediated mutagenicity of o-, m- and p-phenylenediamine were investigated using Salmonella typhimurium TA98. SKF 525-A did not affect the enzyme-mediated mutagenicity of m- and p-phenylenediamine, while 7, 8-BF reduced...
pubmed.ncbi.nlm.nih.gov
Differential effects of retinoic acid and 7,8-benzoflavone on the induction of mouse skin tumors by the complete carcinogenesis process and by the initiation-promotion regimen - PubMed
Differential effects of retinoic acid and 7,8-benzoflavone on the induction of mouse skin tumors by the complete carcinogenesis process and by the initiation-promotion regimen
pubmed.ncbi.nlm.nih.gov
Effects of 7, 8-benzoflavone on skin tumor-initiating activities of various 7- and 12-substituted derivatives of 7, 12-dimethylbenz[a]anthracene in mice - PubMed
Effects of 7, 8-benzoflavone on skin tumor-initiating activities of various 7- and 12-substituted derivatives of 7, 12-dimethylbenz[a]anthracene in mice
pubmed.ncbi.nlm.nih.gov
Dimethylbenzanthracene tumorigenesis and aryl hydrocarbon hydroxylase in mouse skin: inhibition by 7,8-benzoflavone - PubMed
Mouse skin contains aryl hydrocarbon hydroxylase which is highly inducible. The enzyme system is inhibited when 7,8-benzoflavone is added to homogenates of skin epidermis. 7,8-Benzoflavone also inhibits mouse skin tumorigenesis caused by repeated treatment with 9,10-dimethylbenzanthracene or by...
pubmed.ncbi.nlm.nih.gov
Tumor initiation by 7,12-dimethylbenz[a]anthracene in dermal melanocytes of hamster: inhibition through 7,8-benzoflavone - PubMed
Initiation of dermal melanocytes by 7,12-dimethylbenz[a]-anthracene (DMBA) in the dorsal skin of Syrian golden hamsters was investigated for its sensitivity to inhibition by 7,8-benzoflavone (BF). Initiation was carried out by a single intragastric application of DMBA (50 mg/kg body weight) and...
pubmed.ncbi.nlm.nih.gov
In vitro/in vivo effects of 7,8-benzoflavone on aryl hydrocarbon hydroxylase activity of mice - PubMed
The activity of aryl hydrocarbon hydroxylase (AHH) in mouse liver microsomes was assayed in vitro in the presence of 7,8-benzoflavone (7,8-BF). The mice had been previously treated with the AHH inducer 3-methylcholanthrene (MC), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or vehicle (olive oil)...
pubmed.ncbi.nlm.nih.gov
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