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Gonadin - Liquid Steroid Optimizer For Lab/R&D

  1. 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.
    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 more interesting studies I stumbled upon (which has been posted on the forum) demonstrated that administration of vitamin K2 (MK-4) to old rats doubled their testosterone levels without any addition of other stimulating agents like thyroid hormone, or NAD, or even precursors like pregnenolone. More importantly, Vitamin K2 did not affect pituitary hormones like LH, which are typically involved in steroidogenesis. Furthermore, vitamin K1 did not have a testosterone boosting effect so this is yet another reason for chosing MK-4 over K1 (as this question keeps coming up on the forum).
    Menaquinone-4 enhances testosterone production in rats and testis-derived tumor cells

    That vitamin K2 study apparently got the authors thinking what could be the reason behind this effect of boosting testosterone synthesis. Given that the quinone structure is the same in both K1 and K2, the only difference is the side chain. Vitamin K2 contains geranylgeraniol (GGOH) as a side chain, while vitamin K1 does not. So, the same authors decided to do another study using just GGOH as well as a few other related substances and examine their effects on steroidogenesis.
    http://www.tandfonline.com/doi/abs/10.1080/09168451.2015.1123612?src=recsys&journalCode=tbbb20

    As expected, GGOH did boost testosterone levels and in a concentration about the same as the one used in the first study with MK-4 - i.e. 10μM/L - 30μM/L. It also increased the synthesis of progesterone, which is an important direct precursor to steroid synthesis in the gonads, including synthesis of T. So, the testosterone-boosting effects of vitamin K2 (MK-4) appear to be due mostly to that side chain and not the quinone structure, which matches the results from the first study. Moreover, another similar terpene known as Phytol (POH) was even more effective than GGOH in boosting synthesis of both testosterone and progesterone in Leydig cells when used in concentrations of 30μM/L (see attached screenshots).

    Furthermore, the same authors published a new study in which they not only reiterated their belief that phytol and GGOH would raise T levels but also did an in vivo study to confirm their results.
    A novel function of geranylgeraniol in regulating testosterone production. - PubMed - NCBI
    "...Testosterone and progesterone levels in I-10 cell culture mediums markedly increased in the presence of phytol and GGPP, but not in the presence of GOH. Meanwhile, FOH enhanced progesterone, but not testosterone levels. These results indicated that phytol and GGOH have similar effects on testosterone and progesterone production although, unexpectedly, GOH did not affect steroid production in I-10 cells. Recent researches have revealed the biological activity of compounds derived from the isoprenoid/cholesterol synthesis pathway. These isoprenoids, including FOH, GOH, and phytol, regulate various biological processes [47–49]. The results indicated that not only GGOH, but other isoprenoid derivatives, can enhance testosterone and progesterone levels, although the mechanisms by which they exert these effects are yet to be clarified."

    "...We also found that dietary supplementation of MK-4 enhanced plasma testosterone levels in rats, without any alternation of plasma LH levels [45]. Based on the results of our cell-based experiments [32], we conducted further experiments on the effects of GGOH on testosterone production in animals. Eight-week-old Wistar male rats were purchased from SLC Japan (Shizuoka, Japan) and fed either GGOH supplemented (48.3 mg/kg of diet) or control diet for 10 days. Growth performance did not differ between both diets, but plasma testosterone levels in GGOH supplemented group were found to be elevated compared to that of control group, indicating that dietary supplementation of GGOH significantly elevates plasma testosterone levels (unpublished data, Figure 4). These findings provide novel mechanistic insights into the process of testosterone production and may be useful for the development of therapeutic strategies to counter age-associated declines in testosterone levels in men. In summary, the novel role of GGOH in steroidogenesis may bring new possibilities and could be useful in the development of therapeutics for the treatment of men with LOH."

    Since the in vitro tests in the previous studies used the same concentration of phytol and GGOH (100 uM/L), we can use the new in vivo study to estimate the HED dose for phytol. The in vivo study used GGOH in a dose of 48.3 mg/kg of diet in rats, which is 4.83 mg/kg of bodyweight, which is an HED of 0.8 mg/kg. Since phytol has slightly higher molar mass than GGOH the HED for phytol would be 0.816 mg/kg and thus the 100mg a dose of Gonadin provides should be more than enough to replicate this study. As you can see from the attached image, T levels doubled and did so in just 10 days of supplementing!

    Phytol - Wikipedia
    Phytol is quite an interesting substances as it is a precursor to both vitamin E and K and is used as raw material by some organisms who can synthesize these vitamins endogenously. More importantly, both of these vitamins have been found to raise T levels in animal (and some human) studies, which seems to be due to the presence of that side chain (derived from phytol) attached to the quinone ring. In addition, it was also discovered that phytol is a potent aromatase inhibitor with an IC50 of just 1μM/L, which is quite easily achievable with the amounts present is our product. In fact, in this study phytol (code-named SA-20 in the study and attached screenshots) was as effective as formestane (abbreviated FOR in the study and attached screenshots) in inhibiting estradiol synthesis when used in concentration of 1μM/L (see attached image). Formestane is a steroidal aromatase inhibitor similar to but more potent than exemestane. Perhaps even more importantly, phytol reduced mRNA expression of aromatase itself for up to 24 hours, which suggests that it acts as a long lasting "suicide aromatase inhibitor" just like formestane. In concentrations of 10μM/L, phytol was again as effective as formestane in decreasing actual aromatase expression. As mentioned above, the 100mg dose of phytol per serving (8 drops) of Gonadin should achieve 30μM/L concentrations, so the methods of the study on aromatase should be quite easily replicated. Overall, the aromatase inhibition effects of phytol could very well be responsible at least partly for the observed increase in testosterone levels, in addition to the stimulation of StAR. I am not aware of any other substance that can both inhibit aromatase (and long-lasting at that) AND promote endogenous testosterone/progesterone synthesis.

    Two natural products, trans-phytol and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol, inhibit the biosynthesis of estrogen in human ovarian granulosa ... - PubMed - NCBI
    "...Two compounds trans-phytol (SA-20) and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol (SA-48)-were found to potently inhibit estrogen biosynthesis (IC50: 1μM and 0.5μM, respectively). Both compounds decreased aromatase mRNA and protein expression levels in KGN cells, but had no effect on the aromatase catalytic activity in aromatase-overexpressing HEK293A cells and recombinant expressed aromatase. The two compounds decreased the expression of aromatase promoter I.3/II. Neither compound affected intracellular cyclic AMP (cAMP) levels, but they inhibited the phosphorylation or protein expression of cAMP response element-binding protein (CREB). The effects of these two compounds on extracellular regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPKs), and AKT/phosphoinositide 3-kinase (PI3K) pathway were examined."
    "...In the present study out of only 5 terpenoids and 6 steroids examined, one acyclic diterpenoid (SA-20), and one functionalized ergostane steroid, SA-48, potently inhibited estrogen biosynthesis in KGN cells. Currently, these two compounds are the most potent terpenoid and steroid reported to inhibit aromatase in a cell-based assay. Phytol (SA-20) is an acyclic diterpenoid categorized as a branched-chain fatty alcohol (3,7,11,15-tetramethyldexadec 2-en-1-ol). It is found abundantly in nature as part of the chlorophyll molecule, and a relatively high amount of free phytol is present in dairy products (Brown et al., 1993). The finding in this study that phytol is a potent aromatase inhibitor gives new insight on our understanding of the beneficial effects of vegetables and fruit on human health."
    "...We found that SA-20 (phytol) and SA-48 exhibited their inhbitory effect in KGN cells until 12-24 h, indicating that they modulate aromatase at the transcriptional level. This is further supported by the findings that they inhibited aromatase mRNA and protein expression."
    "...In normal breast cells, aromatase expression is primarily derived from the tissue-specific promoter I.4 for transcription, whereas in cells from patients with breast cancer, the expression is primarily derived from the utilization of promoter I.3/II. As a result, estrogen biosynthesis sqitches from regulation by a promoter controlled primarily by glucocorticoids and cytokines to regulation by a promoter controlled through cAMP-mediated pathways by prostaglandin E2 (PGE2), a powerful stimulator of adenylate cyclase (Zhao et al., 1996). Thus, the inhbition of promoter II-driven aromatase expression by means of anti inflammatory cyclooxygenase inhibitors to reduce PGE2 is attracting attention for the tissue specific treatment of breast cancer (Davies et al., 2012)."
    "...Aromatase transcription is primarily controlled by promoter 1.3/II in ovarian granulosa cells. Thus, we examined whether SA-20 and SA-48 exert their inhibitory effects on aromatase transcription through these two promoters. SA-20 and SA-48 at 50uM decreased 20-30% of the promoter I.3 (Fig. 7A). However, at the same concentration (50uM), SA-20 and SA-48 decreased 60%-70% of the promoter II (Fig. 7B). These results indicate that the inhibition of aromatase transcription by SA-20 and SA-48 is mediated through promoter I.3/II, with promoter II playing a more prominent role."

    In summary, phytol seems to be a very versatile substance with a wide array of beneficial effects. As one study aptly summarized these effects include:
    Phytol in a pharma-medico-stance. - PubMed - NCBI
    "...In the pharma-medico viewpoint, PYT and its derivatives have been evident to have antimicrobial, cytotoxic, antitumorous, antimutagenic, anti-teratogenic, antibiotic-chemotherapeutic, antidiabetic, lipid lowering, antispasmodic, anticonvulsant, antinociceptive, antioxidant, anti-inflammatory, anxiolytic, antidepressant, immunoadjuvancy, hair growth facilitator, hair fall defense and antidandruff activities. Otherwise, the important biometebolite of PYT is phytanic acid (PA). Evidence shows PA to have cytotoxic, anticancer, antidiabetic, lipid lowering and aniteratogenic activities. In addition, it may be considered as an important biomarker for some diseases such as Refsum's Disease (RD), Sjögren Larsson syndrome (SLS), rhizomelic chondrodysplasia punctata (RZCP), chronic polyneuropathy (CP), Zellweger's disease hyperpipecolic academia (ZDHA) and related diseases. Thus, phytol may be considered as a new drug candidate."

    Finally, phytol is one of the few known chemicals that raise NAD levels in vivo and thus improve the oxidative state of the organism.
    http://www.tandfonline.com/doi/pdf/10.1271/bbb.130029
    "...In conclusion, we found that phytol increased the blood NAD level via ACMSD protein suppression and mRNA expression in rat liver. It is possible that this mechanism resulted from the activation of PPAR as well of other transcription factors. We will carry out additional studies on the regulation of ACMSD gene expression by phytol to elucidate this issue."


    As the study on POH/GGOH observed, other related terpenes like farnesol or geranylgeranyl diphosphate (GGPP) were not effective in stimulating steroid synthesis, even though farnesol did boost progesterone synthesis but was much weaker compared to GGOH or POH.
    "...We previously reported that menaquinone-4, one of vitamin K2, stimulates testosterone production in I-10 cells via regulation of PKA activity13) and presumed that unsaturated side chain of menaquinone-4, geranylgeranyl group, may be important to express this activity. And we also found that both menaquinone-4 and GGOH have anti-inflammatory activity in lipopolysaccaride-induced inflammation model.5,15) Here, we firstly demonstrated that GGOH stimulates steroidogenesis via activation of cAMP/PKA pathway. Testosterone production is regulated by a complex signaling cascade, with cholesterol transported into mitochondria to initiate steroidogenesis in Leydig cells. Progesterone is an important hormone that is converted to several steroids–including testosterone–and is secreted by I-10 cells.16,17) GGOH stimulated both testosterone and progesterone productions (Fig. 1). Therefore, we measured progesterone levels as a precursor of testosterone in further experiments in Figs. 3(B), 5, and 6(C) to clarify detailed mechanism of GGOH in steroidogenesis."

    As the study describes, endogenous synthesis of steroids by the gonads (and actually peripheral cells as well) is rate-limited by the expression and activity of the so-called Steroid Acute Regulatory Protein (StAR).
    Steroidogenic acute regulatory protein - Wikipedia

    The higher the levels of this protein, the more steroids are synthesize from cholesterol and (maybe even more importantly) from other precursors as well. Cholesterol is not the only precursor to steroid synthesis and we are just beginning to understand the role of these other precursors. But as far as the levels of StAR, GGOH (and POH) increased those level more than 6-fold. I am not aware of any other substance with such dramatic effects on upregulating StAR. Finally, contrary to what other studies have suggested and what some forum members have asked for, PDE levels did not correlate with steroid synthesis. So, a PDE inhibitor will probably not be as effective as a steroid booster compared to GGOH or POH.
    "...On the other hand, we did not find any evidence of a role for PDE in steroidogenesis. StAR functions in the rate-limiting step of steroid production in Leydig cells and is required for the delivery of cholesterol to the inner mitochondrial membrane.26) We showed that GGOH treatment increased the RNA and protein levels of StAR, which acts downstream in the cAMP/PKA pathway. Taken together, our results demonstrate that GGOH enhances testosterone and progesterone production in I-10 cells via induction of cAMP/PKA signaling. These findings provide novel mechanistic insight into the process of steroidogenesis and may be useful for the development of therapeutic strategies to counter age-associated declines in testosterone levels in men."

    As you can see, the authors feel confident that the effects of POH and GGOH may be useful as therapy for declining levels of endogenous steroidogenesis in males. While the study was focused on males, there is evidence that the same steroidogenic process and rate-limiting steps are present in females. Thus, POH or GGOH should have similar beneficial effects in females which is supported by the fact that POH/GGOH boosted progesterone synthesis as much as testosterone. So, I am hoping that GGOH/POH could help both andropause and menopause.

    Inspired by the study above, I searched for other terpenes known to be involved in steroidogenesis and stumbled upon squalene.
    Squalene - Wikipedia
    Squalene is also a very interesting substances as it is actually a precursor to all steroids, including lanosterol and vitamin D. As it seems, squalene (in doses matching the required dose to achieve the optimal concentrations of POH and GGOH in the above study) boosted testosterone levels and dramatically improved the reproductive performance (fertility) in boars. While the study did not delve into the mechanism of action of squalene, it likely involves both its role as steroid precursors and its ability to boost mitochondrial function.
    Feeding with supplemental squalene enhances the productive performance in boars. - PubMed - NCBI
    "...Feeding with squalene at 10 mg/kg/day neither significantly increase the reproductive performance and serum testosterone levels, nor reduced the levels of leptin in boars. Surprisingly, feeding with supplemental squalene at 20 or 40 mg/kg/day significantly improved the reproductive performance as evidenced by dramatically reduced the time for mating, increased semens' volume and motility, and increased the size of litter as compared with that in controls. Furthermore, feeding with a higher dose of squalene significantly reduced the levels of serum leptin, accompanied by elevated levels of testosterone, as compared with that in controls. These data clearly indicate that feeding with squalene can improve the reproductive performance in boars. Therefore, dietary supplementation with squalene may increase the productivity of pig industry and potentially benefit for other animal production."

    And here is another in vivo study (in rats) also showing testosterone increaseing, blood pressure lowering, and leptin lowering effects of squalene.
    Influence of squalene feeding on plasma leptin, testosterone & blood pressure in rats. - PubMed - NCBI
    "...RESULTS: Following squalene feeding, BP and body weight gain were lower in the squalene group. BP was significantly lower from 47 days of age in squalene fed group compared to controls. The levels of plasma leptin, glucose, cholesterol and triglycerides were significantly lower in squalene fed rats than those from the control group at 51 and 75 days of age. However, testicular weights (only 75 days) and testosterone levels were significantly higher in rats from the squalene group than those from the control group at days 51 and 75."

    Squalene is also known to protect from lipophilic xenobiotics like BPA and other aromatic hydrocarbons produced by modern industries, protect from radiation toxicity, reduce cholesterol levels, improve skin health, protect from certain cancers, reduce lipid and muscular lipid accumulation, prevent CVD, and others.

    In addition to the phytol and squalene, 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 evidence for beneficial effects of squalene, phytol, 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 much more judging from the studies in the "References" section below. The doses of squalene and phytol in Gonadin are based on the study of squalene in boars (40mg/kg of diet) and the optimal phytol concentration (30 μM/L) from the in vitro study and the vitamin K2 study. In both cases, about 100mg of each is required to replicate the design of both studies. Like any unsaturated compounds, phytol and squalene have a potential for side effects. Animal studies have shown that at very high doses (10-15 times higher than doses in Gonadin), squalene and phytol can cause liver enlargement and their toxicity profile resembles that of vitamin A. So, it is probably best to stick to the 100mg amounts daily of each substance unless there is a very good reason for going with higher doses. To further lower the potential risk of such side effects related to the unsaturatedness, Gonadin contains vitamin E similar to the common practice to add vitamin E to vitamin A supplements to both prevent peroxidation of the vitamin A and protect from its possible toxicities.

    *******************************************************************************
    Gonadin is a chemical for optimizing endogenous steroid synthesis. Its ingredients phytol and squalene have been shown in scientific studied to both promote the synthesis of steroids from endogenous precursors like cholesterol, as well as potentially serve as steroid precursors themselves. In addition, squalene and phytol have been shown to possess a variety of beneficial effects in animal (and some human) studies including restoring mitochondrial function in aged organisms, lowering cholesterol levels and triglycerides, protection from radiation-induced injury and immunosuppression, improvement of bile acid synthesis, antimicrobial, cytotoxic, antitumorous, antimutagenic, anti-teratogenic, antibiotic-chemotherapeutic, antidiabetic, lipid lowering, antispasmodic, anticonvulsant, antinociceptive, antioxidant, anti-inflammatory, anxiolytic, antidepressant, immunoadjuvancy, hair growth facilitator, hair fall defense and antidandruff activities, etc.


    Units per container: about 30
    Unit size: 8 drops
    Each unit contains the following ingredients:

    Squalene: 100mg
    Phytol: 100mg
    Methyl caprylate: 20mg
    Methyl palmitate: 3.3mg
    Methyl oleate: 3.3mg

    Other ingredients: tocopherols, MCT
    *******************************************************************************

    References:

    1. Miscellaneous
    Absorption and metabolic fate of dietary 3H-squalene in the rat. - PubMed - NCBI (squalene)
    Dietary squalene increases tissue sterols and fecal bile acids in the rat. - PubMed - NCBI (squalene)
    Metabolism of squalene in human fat cells. Demonstration of a two-pool system. - PubMed - NCBI (squalene)
    Fate of intravenously administered squalene in the rat. - PubMed - NCBI (squalene)
    Effects of prolactin, progesterone, and 17beta-hydroxy-5alpha-androstan-3-one on squalene production by the preputial gland of the immature female ... - PubMed - NCBI (squalene)
    Squalene inhibits sodium arsenite-induced sister chromatid exchanges and micronuclei in Chinese hamster ovary-K1 cells. - PubMed - NCBI (squalene)
    Biological importance and applications of squalene and squalane. - PubMed - NCBI (squalene)
    Squalene as novel food factor. - PubMed - NCBI (squalene)
    Squalene: A natural triterpene for use in disease management and therapy. - PubMed - NCBI (squalene)
    The protective role of squalene in alcohol damage in the chick embryo retina. - PubMed - NCBI (squalene)
    The inhibitory effects of squalene-derived triterpenes on protein phosphatase PP2A. - PubMed - NCBI (squalene)
    Fate of intravenously administered squalene and plant sterols in human subjects. - PubMed - NCBI (squalene)
    Feeding with supplemental squalene enhances the productive performance in boars. - PubMed - NCBI (squalene)
    Squalene promotes the formation of non-bilayer structures in phospholipid model membranes. - PubMed - NCBI (squalene)
    Postabsorptive metabolism of dietary squalene. - PubMed - NCBI (squalene)
    Studies on the conversion of squalene to sterol with rat liver enzymes. - PubMed - NCBI (squalene)
    Testicular sterols. VI. Incorporation of mevalonate into squalene and sterols by cell-free preparations of testicular tissue. - PubMed - NCBI (squalene)
    Evaluation of Antioxidant Activity of Phytol Using Non- and Pre-Clinical Models. - PubMed - NCBI (phytol)
    Phytol has antibacterial property by inducing oxidative stress response in Pseudomonas aeruginosa. - PubMed - NCBI (phytol)
    In Vitro Schistosomicidal Activity of Phytol and Tegumental Alterations Induced in Juvenile and Adult Stages of Schistosoma haematobium. - PubMed - NCBI (phytol)
    Phytol in a pharma-medico-stance. - PubMed - NCBI (phytol) (hair-growth effects)
    In vitro anti-quorum sensing activity of phytol. - PubMed - NCBI (phytol)
    Phytol derivatives as drug resistance reversal agents. - PubMed - NCBI (phytol)
    Phytol, a diterpene alcohol from chlorophyll, as a drug against neglected tropical disease Schistosomiasis mansoni. - PubMed - NCBI (phytol)
    Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR. - PubMed - NCBI (phytol)
    Effects of dietary phytol and phytanic acid in animals. - PubMed - NCBI (phytol)
    Effects of phytol, a branched, long-chain aliphatic alcohol, on biochemical values and on hepatic peroxisomal enzymes of rats. - PubMed - NCBI (phytol)


    2. Metabolism/Mitochondria/Diabetes
    Protective effect of dietary squalene supplementation on mitochondrial function in liver of aged rats. - PubMed - NCBI (squalene)
    [SQUALENE: PHYSIOLOGICAL AND PHARMACOLOGICAL PROPERTIES]. - PubMed - NCBI (squalene)
    Phytol/Phytanic acid and insulin resistance: potential role of phytanic acid proven by docking simulation and modulation of biochemical alterations. - PubMed - NCBI (phytol)
    Phytanic acid, but not pristanic acid, mediates the positive effects of phytol derivatives on brown adipocyte differentiation. - PubMed - NCBI (phytol)
    Effects of phytol, a branched, long-chain aliphatic alcohol, on biochemical values and on hepatic peroxisomal enzymes of rats. - PubMed - NCBI (phytol)
    Phytol increases adipocyte number and glucose tolerance through activation of PI3K/Akt signaling pathway in mice fed high-fat and high-fructose diet. - PubMed - NCBI (phytol)

    2. CVD/Cholesterol
    Metabolic variables of cholesterol during squalene feeding in humans: comparison with cholestyramine treatment. - PubMed - NCBI (squalene)
    Sterol synthesis from biliary squalene in the jejunal mucosa of the rat in vivo. - PubMed - NCBI (squalene)
    The effect of the administration of squalene and other hydrocarbons on cholesterol metabolism in the rat (squalene)
    Lipidaemic effects of tocotrienols, tocopherols and squalene: studies in the hamster. - PubMed - NCBI (squalene)
    Effectiveness and safety of low-dose pravastatin and squalene, alone and in combination, in elderly patients with hypercholesterolemia. - PubMed - NCBI (squalene)
    Dietary squalene increases high density lipoprotein-cholesterol and paraoxonase 1 and decreases oxidative stress in mice. - PubMed - NCBI (squalene)
    Squalene ameliorates atherosclerotic lesions through the reduction of CD36 scavenger receptor expression in macrophages. - PubMed - NCBI (squalene)
    Squalene in a sex-dependent manner modulates atherosclerotic lesion which correlates with hepatic fat content in apoE-knockout male mice. - PubMed - NCBI (squalene)
    Cardioprotective effect of squalene on lipid profile in isoprenaline-induced myocardial infarction in rats. - PubMed - NCBI (squalene)
    Effect of squalene on tissue defense system in isoproterenol-induced myocardial infarction in rats. - PubMed - NCBI (squalene)
    Amaranth squalene reduces serum and liver lipid levels in rats fed a cholesterol diet. - PubMed - NCBI (squalene)
    Further in vitro evaluation of antiradical and antimicrobial activities of phytol. - PubMed - NCBI (phytol)


    3. Inflammation
    Dietary squalene supplementation improves DSS-induced acute colitis by downregulating p38 MAPK and NFkB signaling pathways. - PubMed - NCBI (squalene)
    Phytol, a diterpene alcohol, inhibits the inflammatory response by reducing cytokine production and oxidative stress. - PubMed - NCBI (phytol)
    Antinociceptive and Antioxidant Activities of Phytol In Vivo and In Vitro Models. - PubMed - NCBI (phytol)
    Anti-scratching behavioral effect of the essential oil and phytol isolated from Artemisia princeps Pamp. in mice. - PubMed - NCBI (phytol)


    4. Chemoprevention
    Potentiation by squalene of the cytotoxicity of anticancer agents against cultured mammalian cells and murine tumor. - PubMed - NCBI (squalene)
    Antitumor activity of squalene-treated cell-wall skeleton of Nocardia rubra in mice. - PubMed - NCBI (squalene)
    Chemopreventive effect of squalene on colon cancer. - PubMed - NCBI (squalene)
    The preventive and therapeutic potential of the squalene-containing compound, Roidex, on tumor promotion and regression. - PubMed - NCBI (squalene)
    Inhibition by squalene of the tumor-promoting activity of 12-O-tetradecanoylphorbol-13-acetate in mouse-skin carcinogenesis. - PubMed - NCBI (squalene)
    Modulation of doxorubicin-induced genotoxicity by squalene in Balb/c mice. - PubMed - NCBI (squalene)
    Squalene: potential chemopreventive agent. - PubMed - NCBI (squalene)
    The possible role of squalene as a protective agent in sebum. - PubMed - NCBI (squalene)
    An insight into the cytotoxic activity of phytol at in vitro conditions. - PubMed - NCBI (phytol)
    Diol- and triol-types of phytol induce apoptosis in lymphoid leukemia Molt 4B cells. - PubMed - NCBI (phytol)
    Phytol induces programmed cell death in human lymphoid leukemia Molt 4B cells. - PubMed - NCBI (phytol)


    5. Skin health
    The possible role of squalene as a protective agent in sebum. - PubMed - NCBI (squalene)
    High-dose squalene ingestion increases type I procollagen and decreases ultraviolet-induced DNA damage in human skin in vivo but is associated with... - PubMed - NCBI (squalene)
    Squalene as a target molecule in skin hyperpigmentation caused by singlet oxygen. - PubMed - NCBI (squalene)
    Biological and pharmacological activities of squalene and related compounds: potential uses in cosmetic dermatology. - PubMed - NCBI (squalene)


    6. Radiation Protection
    Radioprotection of mice by dietary squalene. - PubMed - NCBI (squalene)


    7. Neurotransmitters/Neuroprotection
    Effects of squalene/squalane on dopamine levels, antioxidant enzyme activity, and fatty acid composition in the striatum of Parkinson's disease mou... - PubMed - NCBI (squalene)
    Phytol a Natural Diterpenoid with Pharmacological Applications on Central Nervous System: A Review. - PubMed - NCBI (phytol)
    Anxiolytic-like effects of phytol: possible involvement of GABAergic transmission. - PubMed - NCBI (phytol)
    Anticonvulsant effect of phytol in a pilocarpine model in mice. - PubMed - NCBI (phytol)
     
  2. This looks fantastic! Thank you very much! My lab rats are dancing with excitement.
     
  3. Impressive as ever.
     
  4. Aww yeah, I never catch these right when they launch. Intriguing stuff.

    Here's the "title-ified" references:

    1. Miscellaneous

    2. Metabolism/Mitochondria/Diabetes

    3. CVD/Cholesterol

    4. Inflammation

    5. Chemoprevention

    6. Skin health

    7. Radiation Protection

    8. Neurotransmitters/Neuroprotection
     
  5. Wow, you're on a roll! Good stuff, Haidut.
     
  6. Yeah, I am pretty excited too. If it turns out that this can indeed help age-related hypogonadism without any shutdown or change in LH levels it would be pretty big deal. I suspect adding some pregnenolone and/or DHEA may make it even more powerful.
     
  7. Thanks! Btw, two more supplements coming next week so should be pretty productive month :):
     
  8. Can't wait to see them!
     
  9. Thanks Dan! I wonder why does the forum sometimes fetch the titles itself and why sometimes it seem to give up mid-way through pulling them. Is there a limit on how many titles it would pull automatically? Maybe @charlie would know?
     
  10. I can't remember the exact details, but while there was a couple things Charlie could tweak, it never seemed to make it through big lists of links.
     
  11. @haidut

    When you first mentioned squalene as a possible component of TocoVit, I recalled a caution from Andrew Kim:

    "Free fatty acids and squalene are major lipids that make up sebum. Squalene is highly unsaturated in structure and highly susceptible to peroxidation and photodegradation. The byproducts, squalene peroxides, promote acne, roughening of skin, and wrinkling.5,6 The free fatty acids, when polyunsaturated, degenerate to promote the peroxidation of nearby lipids, including squalene, whereas saturated fats do not."

    Not sure on the current state of the research though
     
  12. If I'm not mistaken these are all natural chemicals?
     
  13. @haidut any information on the safety of these compounds in humans?
     
  14. dude, I love you, no homo:)...but seriously I'm extremely excited! I respond very well to K2 (it shoots my libido up big time) so this is very interesting to me and not only that but it can increase the function of the gonads and provide skin and hair benefits? No brainer...ordered.

    I'll log it when I get it.

    And no DMSO :D
     
  15. @haidut do you think this would have an effect on a rat with high FSH?
     
  16. Are they also going to be directly androgenic ?
     
  17. Would it be better to apply this on the testicles (of a male rat) or will any area work just as well?
     
  18. But is it actually squalene or squalane containing? Some of the studies linked here point out to both indistinctly. From what I read it seems to be a strong generalized ethic concern with shark derived squalene, while the squalane being the better approach for skin hydration.


    "Squalane is derived by hydrogenation of squalene. It is naturally present in the skin lipid barrier of plants, animals and humans, preventing moisture loss while restoring skin’s suppleness and flexibility.
    Due to the complete saturation of squalane, it is not subject to auto-oxidation. This coupled with lower costs make it desirable for cosmetics where it is used as an emollient and moisturizer.
    The EU took steps to ban targeted deep‐sea shark fisheries back in 2010. However, consumers willing to buy ethical products cannot choose specific plant based squalane ones because differentiation between the substance of origin is not required in labeling requirements."

    Squalane versus squalene, are you aware of what you may be paying for?
     
  19. Do we have any idea on how much progesterone would be boosted from this product?
    Do you know how much squalene there is in tocovit yet?
     
  20. Well, some comments
    In fact, it should be stated that it was observed to be more effective at 30μM. Otherwise, at 10μM the outcome was worse than GGOH and close to control.
    What lead me to the question, about how much is the dose required to reach 30μM/L concentration?


    So for testosterone levels to increase it took higher dose than 40mg/kg/day. For average 80kg male this would mean a dose higher than 3gr. of squalene.
     
  21. There is a hard coded time limit, no way to change it. So after it times out on pulling the title over, it goes ahead and submits the post even if all titles were not pulled. Also I notice Pubmed is very slow to respond at different times. So the way around this is to click edit, then hit "save changes" so that it will go through the process again for the rest of the links that were not done. I went ahead and did it for your OP. It took a few times but it did get them all done.
     
  22. Isn't Squalene the dangerous substance used in vaccines? I'll have to lookup references, but I remember reading that injecting it can basically cause PTSD (tests on soldiers - my memory might not be serving me right, though).
    EDIT: I release this source isn't trustworthy, but reading the cautionary - even if bogus - tales of a substance is probably a good idea before taking it:
    Million TIMES More Squalene In H1N1 Vax Than Caused GWI !!
     
  23. Yes, it is similar to vitamin A in that respect. But one of the studies I posted above in the "Skin health" section deals exactly with the presence of squalene in the sebum and concludes that it is there as a protective mechanism. Also, the amount in Gonadin is not that much, and it matches the study in boars. So, I used the minimum amount that was shown to have a highly beneficial effects. Finally, there is sufficient vitamin E in Gonadin to protect from any peroxidation issues with squalene.
     
  24. Yes, they are.
     
  25. A good number of the studies in the References section are on humans. There were no toxicities as far as I could see.
     
  26. Lol, glad to hear it. Yes, please keep everybody posted on experimental results.
     
  27. Not sure, the studies showed no effects on pituitary hormones but if it increases progesterone enough that should trigger the negative feedback mechanism and lower FSH.
     
  28. I'd say its thimerosal -along with formaldehydes- the most dangerous one.
     
  29. Not directly. One of them is dopaminergic, anti-serotonin, anti-cortisol, and a powerful HDAC inhibitor (anti-cancer). The dopamine and anti-cortisol effects may lead to improved steroid profile though. The other one is an electron withdrawing agent and it is sold as a drug for improving heart function and metabolism in some countries. It is not related to Mildronate though.
     
  30. I think the scrotum application would also work and should be able to achieve the same with much lower dose. But given that many tissues can synthesize steroids, you may want the systemic effects as well.
     
  31. It is squalene. The saturated version squalane was not shown to have effects on steroidogenesis.
     
  32. Ah, sorry for the conflation. I'll look into what possible actions it has in the blood. Interesting how one could have (supposedly) such toxic effects, while the saturated not having them.
     
  33. OK, I will change that in the original thread. The 30uM concentration was the same they used in the vitamin K study and that study replicated the results in vivo using vitamin K2 in a HED of 1mg/kg. So, for most people 70mg - 100mg vitamin K2 daily should replicate that study. But no all of those 70mg-100mg vitamin K2 is geranylgeraniol. So, to be conservative, I put 100mg phytol just to be sure. To achieve 1uM concentration you need about 3mg phytol. So the 100mg per dose seems to be good.
    Finally, the study in boars used 40mg/kg of diet, not bodyweight. From the study:
    "...Experimental groups of boars were treated with 10, 20 or 40 mg/kg/day squalene in 1 kg basal diet, respectively (Healthy Nature Resource, Inc., Walnut, CA, USA) and then were fed with 1.5 kg basal diet and 0.5–1.0 kg green feed daily."


    The conversion factor from pigs to humans is about 1:1 so this means 40mg/kg of diet in humans as well. Given that humans consume on average about 2.5kg of food daily, you get 100mg of squalene. Btw, the lower dose of 20mg/kg also had an effect and it was not that far off from the 40mg/kg but given that an overall dose of 100mg daily would not be that much and I wanted to keep things simple I went with that amount per dose.
     
  34. Great, thanks!
     
  35. Possibly, when injected. Squalene is present in (real) olive oil in about 0.5% concentration. So if you eat about 30g of olive oil you'd get that amount of squalene. I am not aware of anybody getting side effects from dietary squalene.
     
  36. @haidut

    Have you yourself used this product yet, and if so, what were the effects you noticed?
     
  37. Yes, it increased my T levels by about 30%.
     
  38. What's the argument for taking a synthetic supplement of something that can be consumed naturally in a food? Even Peat recommends against such things - he said its much safer to eat coconut oil than to take the "MCT oils" ..
     
  39. OK, so it changed a number on a paper, but were there any signs and symptoms that improved, physical or mental changes?

    and any side-effects?
     
  40. There is no argument, it is a supplement - i.e. to supplement diet, not replace it. Some people may not want to ingest 30g of olive oil daily to get 100mg of squalene. And I am not even sue what food would give you 100mg phytol.
     
  41. N/M - answered
     
  42. No side effects. It improved weight lifting capacity and mood. I am not sure if this is due to the T boost or the dopaminergic effects squalene showed in one study.
     
  43. This study discusses possible squalene-mediated virgin olive oil beneficial effects,

    "Squalene, first isolated from shark liver oil and named by Tsujimoto in 1916 [8], is a polyunsaturated triterpene containing six isoprene units and a biochemical precursor of cholesterol and other steroids [9]. Squalene content in extra virgin olive oil is especially high, up to 0.7% (7 g/kg), compared to other oils and human dietary fats [10], [11]. In vitro, it is a highly effective oxygen scavenging agent [12]"
    Dietary Squalene Increases High Density Lipoprotein-Cholesterol and Paraoxonase 1 and Decreases Oxidative Stress in Mice

    So a single tbsp of olive oil contains up to 100mg squalene woww, I've been taking evoo almost all my life and so squalene without knowking. I always swore by olive oil, god knows what pile of other countless unknown substances it contains.

    I think for pushing those properties as a supplement, the ideal should be going on higher doses than obtained normally through food, to see if there is an increased effect. Or give a try to its saturated version,
    "Squalane is a saturated form of squalene in which the double bonds have been eliminated by hydrogenation. Squalane is less susceptible to oxidation than squalene" - Squalene - Wikipedia

    which in Peat land it could be suggested to be superior for being fully saturated, under the principle: "saturated is always better, polyunsaturated tends to be the opposite".
     
  44. Squalene. The miraculous essential omega 2 oil. Secrets from the sea

    "The biochemical structure of squalene is C30 H50 (C30:6n-omega2) all trans isoprenoid"
    "Squalene an omega 2 fatty acid has unlike omega 3 fish oils more complete and effective chemic groups."
    "As an omega 2 fatty acid squalene has a redox function which releases oxygen from water, resulting in this above mentioned increased oxygen level in the cells."

    Lol you're promoting and omega supplement!! can't wait to know what Peat thinks of this compound... my guess is that he will be skeptical because its pufa structure.
     
  45. Im not sure of that interpretation about the dose being based on kg. of food. I would say it is per kg of body weight. If it were as you say, then why to specify "/day"?. If it were based in the kgs of food, the "/day" would have no sense, it would add no info to the calculated amount.
     
  46. The squalene in Gonadin is mostly as a booster. The primary ingredient is Phytol as that is what increased StAR activity 6-fold and T/progesterone levels several fold. The squalene in commercially sold EVOO was tested a few times and it was found to be very low. I think it was in one of the Consumer Reports or something. Higher amounts of squalene probably get in the danger zone due to their unsaturatedness. As I mentioned, squalane is not an option as it was not found to have the beneficial effets of squalene. Look at the References section. There are few studies that compare squalene and squalane. You can also search Pubmed for "squalene squalane".
    Effects of squalene/squalane on dopamine levels, antioxidant enzyme activity, and fatty acid composition in the striatum of Parkinson's disease mou... - PubMed - NCBI
    "...Squalane increased thiobarbituric acid reactive substances, a marker of lipid peroxidation, in the striatum. Both squalane and squalene increased the ratio of linoleic acid/linolenic acid in the striatum. "
     
  47. That is how it is usually specified. The "daily" reference has no bearing. They also discuss "basal diet" vs. supplemented one. And if that was not enough, in the Discussion section they have this excerpt.
    ".... In our study, the major components of basal diet were soybean and corn, the green feed was pumpkin, so the squalene content was very low and could be ignored compared with experimental addition (10, 20 or 40 mg/kg/day squalene). It almost did not affect our results".

    So, the discussion is about the squalene content in basal diet vs/ squalene content in supplemented diet. But just to make sure, I will email them and ask for clarification. Finally, the squalene is there just as a booster. The phytol is the primary ingredient as I mentioned in a post above.
     
  48. Lol, vitamin A is also highly unsaturated. Are you taking vitamin A? Considering the amounts present in Gonadin (100mg - 200mg daily) you probably get more PUFA from your vitamin E supplement if you bought it from the store. Gonadin also contains vitamin E so it should protect from any theoretical risks form this small amount of unsaturated compounds.
    Finally, if you had taken the time to actually read even the Wiipedia page on squalene (and the original post in the thread) you would have seen that squalene is a precursor to ALL steroids in humans, including vitamin D, and of course cholesterol and lanosterol. So, apparently we do have a use for squalene.
     
  49. Yeah, it was just a joke :) Btw, why you didn't put GGOH in it too, to make it more "complete". Did you considerate it and discarded the idea for some reason?

    How much GGOH is in mk4, and how much would be the dose of mk4 to achieve 30μM of GGOH?
     
  50. I did consider adding GGOH, but so far have not been able to find a vendor that can provide pure bulk amounts. I'll keep searching though as GGOH has a lot of studies behind it for various other benefits. The thing is though, GGOH is a precursor to squalene so using squalene probably accomplishes what GGOH would do. As far as the the dose required to reach 30uM/L, basically GGOH and POH have almost the same molar mass and the doses should be about the same. The first study with vitamin K2 (MK-4) used a HED of about 1mg/kg to replicate the 30uM in vitro concentration. I even sent them an email about it and the authors responses saying that indeed the 1mg/kg human dose should acheve 30uM/L vitamin K2 in tissues and that is how they chose the in vivo rat dose (~7mg/kg) Now, given that only a portion of the vitamin K2 molecule is actually GGOH (and taking into account the molar mass of the quinone portion and GGOH prtion) it means of those 30uM/L concentration vitamin K2 about 66% is GGOH. So, the effective concentration of GGOH in the vitamin K2 study was about 20uM/L, assuming it was only GGOH that had T boosting effects as the second study with GGOH and POH actually claims. Just to make sure, I went with 100mg per dose for both POH and squalene as it would achieve 30uM/L as the second study with GGOH and POH found 30uM/L to be optimal.
     
  51. Going from 980 to 1250 should probably have some very significant effects. How much did your lifts go up?

    Does this supplement increase anabolic to androgenic ratio or keep it the same because of t>dht conversion?
     
  52. How much were you taking, how (orally , topically (on scortum?)) and for how long?
     
  53. DHT probably went up as gonadin was shown to be anti estrogenic so estrogen wouldn't rise and DHT most likely will go up when free T does as that would be the only open pathway.
     
  54. The same dose as in Gonadin, for a few weeks. I have not tried phytol on its own yet but that would be the next experiment.
     

  55. Wow you ARE a total homo-sapien!!

    I just submitted my order for a case of 20. Why so many? I have been orderring in bulk for when the corrupt feds come for my authentic meds.

    Question: Are you still using selsun blue for selenium on the scalp?
     
  56. Cant find where to order. Am I blind?
     
  57. Trimetazidine maybe?
     
  58. Nope, like I said, not related to Mildronate. Trimetazidine was under consideration as a separate supplement but FDA has given indication that it will treat it as prescription drug due to its status as a banned drug by WADA.
     
  59. yes, papi
     
  60. Oh yeah, they're both beta oxidation inhibitors. Brain fart.

    And Trimetazidine's a dopamine antagonist anyway unfortunately.
     
  61. Yes, the Parkinsonism it induces was another reason I decided to not release it. And now we know that niacinamide is also a fatty acid oxidation inhibitor just like Mildronate in reasonable human doses (<1g daily). So, there is really no reason to go with something more obscure and less tested. Hard to beat niacinamide in terms of safety.
     
  62. I have a question, does Idealabs sell anything that raises DHT? I know they used to sell 11-keto DHT but I don't know if they still. Is there anything else they sell which raises DHT?
     
  63. Androsterone.
     
  64. Thank you
     
  65. If I understand it correctly this product is useful even for those of us with low cholesterol?
     
  66. Pansterone may also raise DHT in tissues and maybe even in serum if applied to the scrotum.
     
  67. That I don't know. The study with geranylgeraniol and phytol only looked at the effects on stimulating StAR and cAMP, but raw material like cholesterol was needed. So, low cholesterol levels may be in impediment. That is why I added squalene as it is known to convert into cholesterol and other steroids in humans. So, the way I look at it - phytol is the spark and squalene is the fuel, but there may be additional pathways we don't know about. I would still try to raise cholsterol levels though if they are low. Sugar and coconut oil seem to be the best methods.
     
  68. 30% is pretty hefty for sure. I am trying to think of how it can be used to help those on TRT...or maybe to transition off TRT (if they so desire). Would it continue to raise T levels for those on TRT in your opinion?
     
  69. Interesting! Could this be used as a substitute for testosterone replacement therapy ?
     
  70. @haidut

    Thoughts on this?

    “Adult male and female inbred C57BL/6J mice were split into three groups (six/group) and given supplemented diets for 19 days. One group was supplemented with 0.5% phytol to study liver toxicity and animal mortality. The phytol-fed mice ingested approximately 250 mg/kg (10 mg/kg body weight/day). Control-fed female and male mice consumed food and gained weight at a similar rate, only females on the phytol diet lost weight (after 10 days). The weight loss was preferentially in fat tissue versus lean muscle. Phytol-fed male mice showed gross enlargement of the liver as indicated by a 27% increase in liver weight over male mice fed control food. Livers appeared normal based on gross examination. Phytol-fed females showed gross morphological changes in the liver when compared to control-fed females. Livers were consistently pale and friable, with a generalized mottled appearance. Histopathology revealed lesions, random hepatic cord disruption, and small multifocal areas of hepatocytes necrosis with early inflammatory cell infiltration of neutrophils and lymphocytes present in phytol-fed females (Atshaves et al., 2004).”

    From: http://www.sciencedirect.com/science/article/pii/S0278691509005286
     
  71. Will the aldosterone and potassium channel inhibition be decreased (or increased) if applied to scrotum? Specifically referencing Pansterone (and/or Androsterone and/or Gonadin) here.
     
  72. Anyone want to report their anecdotes with this yet?
     
  73. The 250mg/kg mouse dose corresponds to about 1g - 1.5g daily dose for a human. That's pretty high. As an unsaturated compound it an cause liver enlargement in those doses. The dose in Gonadin is an order or magnitude lower and it also has vitamin E to protect from any potential toxic effects of the unsaturation. The study used 30uM, which roughly corresponds to 100mg dose in humans. Same for squalene. I do not recommend abusing this and gobbling it up like candy. Vitamin A can have very similar toxicities when abused.
     
  74. If you have a question about Pansterone then please ask it in that thread. I don't see anything about squalene and phytol that would imply such effects for Gonadin.
     
  75. Wouldn't the oral vs transdermal route also make a big difference?
     
  76. Yes it can, as with topical it may have lower overall toxicity by avoiding the liver.
     
  77. Does this supplement increase endogenous 11 keto?
     
  78. There is no data on that, but if it increases endogenous T and inhibits aromatase then it should increase DHT as well.
     
  79. Did you pull Gonadin? Or ran out of supply?
     
  80. It's in the lab research section (add /lab to the usuall address).
     
  81. Mine is arriving today. Question @haidut I am planning on applying to scrotum as well as a couple drops to face (to support facial hair growth). Is it OK to apply before bed, or does it have a stimulating effect that might keep one awake at night?

    Also, I am currently using the Andro plus pansterone combo and having great results with mood, muscle (I lift weight a few times a week) etc. Would it be over kill to use together with this or just synergistic for boosting androgens and possibly test levels? Thanks!
     
  82. Btw my goals are to increase muscle mass, decrease body fat (prob at about 15 percent) and of course, support a healthy metabolism.
     
  83. I don't think it has stimulating effects so it should be usable at any time during the day. I would use on its own for at least a week to see it effects before stacking with anything else.
     
  84. I just got mine from papi H.

    I am eating and will take some orally. Should I started with 8 drops ?
     
  85. Yes, that's what I would start with on a rat but given that it contains MCT and tocopherol it can probably be taken an empty stomach as well.
    Keep us all posted please.
     
  86. Rat took 8mg, so far I felt an increase in mood, feels like a pro GABA effect but not totally like other GABA agonists, just feel good. Kinda like a similar feeling after taking high dose of K2 mk4, but more prominent. Other than that don't notice anything else yet. I plan to try 16mg tomorrow.

    I like the new dropper bottles though and it comes out very very easily.
     
  87. Applied 3 mg to rat's testicles and 5 to forearm. He didn't take this supplement by itself so I will have do that tomorrow. But so far results are promising. Huge increase in mood and libido. Will provide further details when he gets a better feel for the substance.
     
  88. Rat dosed with 8drops last night. 2 on face, 4 under tongue, 2 on scrotum. Rat has been doing "no FAP" for 60 days. Last night after applying gonadin and going to sleep, rat had a wet dream (first one since started on no fap). Rat slept deep, woke up 30 min before alarm this morning, and is voraciously hungry this morning.
     
  89. BTW, are we better off putting this in rat's food, or applying topically?

    Why did you choose tocopherol instead of DMSO?

    Would there be any risk or concerns about applying it on top of DMSO, pansterone for example?
     
  90. You mean 8mg or 8 drops? The recommended dose is 8 drops, and it has 100mg phytol and 100mg squalene. Btw, I am about to update the main thread with some more information from the phytol study on aromatase. It looks like in the same concentrations (1uM) phytol was more potent than formestane (a steroidal aromatase inhibitor similar to exemestane) in inhibiting aromatase. Perhaps even more importantly, phytol was very active in inhibiting the abnormal upregulation of aromatase, which (as the study discusses) is under the control of cortisol and inflammation.
     
  91. I personally like its effects more orally as it allows for its systemic effects. Many tissues synthesize steroids and many tissues express aromatase. So, oral use should give better chance to upregulate the former and inhibit the latter. As far as solvents - I like the effects more when it was dissolved in tocopherol than in DMSO. Since Gonadin is a topherol/oil formulation I would not mix with the DMSO supplements at the same time.
     
  92. I really think this reduces cortisol. My rat painted 8 drops on his ratsack and woke up in the middle of the night with symptoms of lower blood sugar/cortisol. Rat felt very relaxed 30 minutes after taking it. Rat possibly had higher libido, today. (Not entirely sure if this is related. Rat was in the big apple with lots of hot girls and women seemed to respond more positively even with no sleep)
     
  93. Same thing happened to me on the first night of using it :) I have been using nothing but Gonadin (daily at 8 drops) for the last week and honestly I may upgrade it to my favorite "male" suplpement so far. My muscles grew and don't even train any more. Had a few pimples appear on my face, which in the past always coincided when T levels went above 1200. Will do another blood test in a week to confirm.
    Btw, you may want to look at the original thread again. I updated it with more quotes from the effects of phytol on aromatase. If this works in vivo as it worked in vitro, phytol is nothing short of amazing!
     
  94. Yeah, I meant 8 drops, it won't let me edit my post above.

    I did 16 drops this morning today. What I have noticed:

    • Temps are definitely up, I was just sitting in the office all day today and mildy sweating most of the time despite really doing nothing
    • Muscles are definitely more full and my waist is tighter
    • The mood increase is definitely noticeable right after dosing
    • Libido increase for sure
    • hunger is up
    I took it around 9:00am this morning and my temps are still up and muscles still feel pumped. I'm wearing long sleeves today so it was hard to notice until I left work and started to carry grocery bags and my muscles got much more super pumped and hard despite not being in the gym for the past few days. It kind of feels similar to androsterone.

    I assume the effects are still going to progress as the T levels increase maybe at least until the one week mark. I will probably know more when I train in the gym too...I really like this stuff

    Thanks for that aromatase study too, this stuff definitely has estrogen lowering effects.
     
  95. One of the most reliable signs of higher T levels is "morning wood" and spontaneous erections even without stimulation. If you are having these then it is probably having the desired effects :):
     
  96. Good, similar effects to mine (on muscles). Not sure if you saw my post about updating the main thread. It looks like phytol is a long-lasting suicide aromatase inhibitor as potent as formestane/exemestane. I think even without the T boost, just inhibiting aromatase so potently and for so long would produce these effects we are observing. Can't wait for my blood tests next week.
     
  97. I had this the moment I applied Gonadin. Needless to say I think it's working