Let’s start from the top. Testosterone synthesis begins in the hypothalamus, then the pituitary and then the testes. GnRH -> LH -> testosterone synthesis.

However, some compounds can actually increase testosterone synthesis without affecting LH levels or sensitivity.

In this article I want to cover a variety of compounds that can increase testosterone, either by increase LH, boosting StAR (the rate limited step in steroidogenesis) and lastly, but increasing enzymatic activity of those enzymes that convert pregnenolone to testosterone.

#1 Cordyceps

Both Cordyceps sinensis and militaris are parasitic fungus that parasitizes insects.

Cordyceps sinensis is classified as a medicinal mushroom, and its use has a long history in traditional Chinese medicine as well as traditional Tibetan medicine.

Traditional healers in Sikkim recommend the fungus/mushroom Cordyceps sinensis for “all illnesses” as a tonic, because they claim that it improves energy, appetite, stamina, libido, endurance, and sleeping patterns (R).

Cordyceps (sinensis and militaris) has been shown to increase testosterone in animal models, and cordycepin plays a big role in this.

The polysaccharides and/or glycoproteins in Cordyceps sinensis may be similar to luteinizing hormone in structure and have the ability to recognize luteinizing hormone receptors on Leydig cells to stimulate testosterone production (R).

Cordyceps sinensis are also able to activated both PKA and PKC signal transduction pathways, which stimulate cell steroidogenesis, by promoting StAR (R).

Cordyceps can also increase the protein levels of androgen receptors, FSH receptor, and LH receptor (R).

This study found that cordyceps militaris increased the secretion of testosterone and DHT by primary testicular cells, while no changes in the mRNA expression of steroidogenic enzymes were found (R).

Additionally, the aphrodisiac activity of C. sinensis has been reported because of the testosterone-like metabolites and libido-promoting activity (R). 

In summary, Cordyceps can increase testosterone:

• without increasing LH
• through LH mimetic compounds
• by increasing LH receptors
• by upregulating StAR, which is the rate-limited step in steroidogenesis
• or exert testosterone-like effects, with its testosterone-like metabolites

Supplements

• 30% cordyceps sinensis dual extract (10% off code) (SA orders)
• Nootropicsdepot (10:1 dual extract)

#2 Longdan Xiegan Tang

Long dan Xiegan Tang is a Chinese herbal combination, long used for lowering prolactin, reducing insomnia and supporting the liver (removes heat from the organs according to TCM).

This study found that Long dan Xiegan Tang extract inhibits pituitary estrogen receptors (R).

The administration of estrogen to aromatase-deficient men discloses the effects of circulating estrogens on LH secretion, exerted both at pituitary level, as shown by the decrease of basal and GnRH-stimulated secretion of LH and the LH pulsed amplitude, and at hypothalamic level as shown by the reduction of the frequency of LH pulses.
…circulating estrogens play an inhibitory role in LH secretion by acting on the hypothalamus and the pituitary gland of men.

Reference

Estrogen receptors in the pituitary not only inhibit LH release, but also increase the release of prolactin, growth hormone, ACTH (R), oxytocin (R) and TSH (R, estrogen prevents to TSH suppressive effect of T4).

Long dan Xiegan Tang has been shown to lower prolactin induced by anti-dopamine drugs, mainly by 1) antagonizing estrogen receptors in the pituitary, 2) restoring olanzapine-induced decrease in protein expression of the key components of the TGF-beta1 signaling, TGF-beta1, type II TGF-beta receptor, type I TGF-beta receptor and phosphorylated SMAD3 in the pituitary and hypothalamus and 3) restoring pituitary and hypothalamic dopamine D2 receptor (D2R) protein level (R).

Other pituitary estrogen receptors antagonists that are widely used as testosterone boosters are tamoxifen, clomid, etc, however, they also have other side effects.

• Long Dan Xie Gan Pian

#3 Fructus Hordei Germinatus (FHG)

Although FHG is mainly used for lowering prolactin, as documented in the ancient book Zhonghuazi of Song Dynasty, it can also help to restore low testosterone, induced by low dopamine and high prolactin.

FHG has been shown to have an obvious curative effect in treating hyperprolactinemia in rats (R). It’s been shown to increase serum estradiol, progesterone, FSH and LH levels back to normal, while
decreasing prolactin, pituitary prolactin positive cell number and mRNA expression level as well as inhibiting the hyperplasia of mammary gland in hyperprolactinemia model rats effectively.

FHG is also able to restore dopamine signalling, which then boosts testosterone levels, since dopamine increases cAMP/PKA, which stimulates StAR.

• FHG

#4 Tiancan Zhuangyang Powder

This seem like a very interesting Chinese herbal mix, but apart from a few abstracts, I can’t find a full study explaining what’s in this mix. I also can’t find a vendor selling it. If anyone knows more about it or know where to buy it, please let me know.

TCZYP could prevent serum TT and FT levels from decrease, improve StAR protein activities, and attenuate the depression state and muscular tension in PADAM [partial androgen deficiency of aging male] rats. Its action was equivalent to that of testosterone propionate.

Reference

Like most other herbs that improve sexual function in TCM, this mix tonify Yang energy in the kidney, which is responsible for its benefits.

#5 Vitamin K2 (MK-4)

This supplement is part of my “outstanding stack for bigger balls (and higher libido)” and the following text I just copied out of that article.

In short vitamin K2 (MK-4) has been shown to increase testosterone through a LH independent mechanism, mainly by upregulating StAR.

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There are multiple animal studies showing that vitamin K (only MK-4) boosts testosterone production by increasing StAR, which is the rate-limited step in transporting cholesterol into the mitochondria for conversion to pregnenolone.

In this study, rats were given 75mg/kg MK-4 for 5 weeks and their testosterone increased significantly. MK-4 is the predominant vitamin K form present in the testes.

The MK-4 increases protein kinase A (PKA) signaling, which stimulates the steroidogenic acute regulatory protein (StAR) to transport cholesterol from the outer to the inner mitochondria. Furthermore, MK-4 increases CYP11A activity and also its mRNA gene expression. CYP11A is the enzyme that converts cholesterol into pregnenolone (the first steroid).

The increase in testosterone is independent of LH secretion as LH remains unchanged with vitamin K2 administration.

As the study concluded: “expression of CYP11A, the rate-limiting enzyme in steroidogenesis, and phosphorylation levels of protein kinase A (PKA) and the cAMP response element-binding protein were all stimulated by the presence of MK-4” (R).

Although that’s a really big dose used in the rat study, direct testicular application of vitamin K2 could spot specific increase local concentrations of vitamin K, thus exerting the same effects are oral doses of vitamin K. Oral absorption of vitamin K is very low, and then the liver and all other tissue in the body get their share, so only a small amount reaches the testes.

Also, vitamin K is important for the post-translation of Gla proteins in various tissues, including the testes and is directly involved in steroidogenesis. The mRNA of steroidogenic genes is low in vitamin K deficient tissue.

Furthermore, vitamin K2 increases osteocalcin, which acts on Leydig cells of the testis to stimulate testosterone biosynthesis and therefore affect male fertility. More on osteocalcin here and how to boost it.

Vitamin K boost dopamine and lowers serotonin

Serotonin is a major inhibitor of testosterone production and it correlates very well with prolactin. Prolactin is well known for inhibiting libido and fertility.

Dopamine on the other hand promotes libido and sexual function.

Vitamin K2 and other quinones (such as beta-lapachone, emodin, PQQ, etc) enhance serotonin uptake (by redox modification) and increase dopamine levels, by inhibiting MAO-B (R, R, discussed in this thread).

Vitamin K2 lowers estradiol

As mentioned earlier, estrogen causes vascular dysfunction and contributes to sexual dysfunction. Vitamin K2 can actually lower estradiol.

This study found that vitamin K2 binds to 17beta-HSD4, a key enzyme that regulates important redox reactions at the C17 position of steroid hormones, converting estradiol (E2) to estrone (E1).

We found in the present study that vitamin K2 decreased E2:E1 ratio and inhibited the amount of ERa-DNA binding in a dose-dependent
manner, although the precise relationship between the binding and functional modulation of vitamin K2 by 17h-HSD4 remains to be elucidated. These results may provide new knowledge of the linkage
between vitamin K and estrogen function.

Reference

Vitamin K2 improves mitochondrial function

Improves mitochondrial function. a study in Drosophila proposes vitamin K2 as a promising compound to treat mitochondrial pathology. In this study, MK4 can act as a mitochondrial electron carrier, like ubiquinone, facilitating ATP production, rescuing mitochondrial defects and restoring its function. Vitamin K2 combined with vitamin C supported ETC function and ATP production, thus improving glucose oxidation and lowers lactate and we all know by now how essential proper energy metabolism is in the testes for testosterone production (R).

Few additional benefits of vitamin K2. Vitamin K2:

• Improves neurological health (R). Neural damage is a major reason why people get erectile dysfunction, and it can be caused by excess gut issues, excess iron, PUFA accumulation, etc.
• Inhibits 12-lipoxygenase (12-LOX) and protects against oxidative stress in the testes (R).
•  Lowers concentrations of inflammatory markers in vivo, and exerts an anti-inflammatory role by suppressing nuclear factor κB (NF-κB) signal transduction (R).
• Inhibits endotoxin increased inflammation (R).
  • After LPS treatment, plasma testosterone levels were significantly reduced in the vitamin K-free diet group compared with the control diet group. Testicular mRNA and protein levels of Cyp11a, a rate-limiting enzyme in steroidogenesis, corresponded to plasma testosterone levels. However, plasma luteinizing hormone levels were unaffected by diet and LPS. Phosphorylated nuclear factor κB p65 in the testis was significantly increased in the LPS-treated, vitamin K-free diet group compared with control. These results indicate that dietary vitamin K affects testicular vitamin K levels and ameliorates the LPS-induced reduction in testicular testosterone synthesis. Testicular vitamin K might facilitate the inhibition of inflammation signal transduction and maintain steady levels of testosterone (R).
• Inhibits lipid peroxidation (R).
• Promotes sperm maturation. “Vitamin-K-dependent γ-glutamyl carboxylase (GGCX) and matrix Gla protein (MGP) were essential in extracellular calcium signaling of the intercellular communication required for epididymal sperm maturation” (R).

Dosing

After my evening shower, I apply 5 drops of Kuinone (which gives me 10mg K2) on my scrotum and then read a book for 30 minutes just so that it can be absorbed completely.

#6 Aspirin

Good old aspirin is one of my favourite multifunctional supplements.

COX2, the enzyme that uses arachidonic acid (an omega 6 made from linoleic acid) to create highly inflammatory prostaglandins, are inversely correlated with StAR protein in the Leydig cells.

It was found that inhibition of COX2 activity with DFU, as assessed by measuring prostaglandin E2 levels, increased blood testosterone concentrations (P < 0.05) and StAR protein in Leydig cells in a dose-dependent manner.

Reference

This human study has found that aspirin is able to increase testosterone levels in humans.

…The main result of this study is that in our group of moderately trained athletes, a short-term ASA treatment compared to placebo was associated to significantly reduced after-treatment morning plasma F (cortisol) absolute concentrations (Fig. 1). Also, significant differences in the absolute and percentage of variation for F, T, and T/F ratio were observed. In particular, F concentration showed a significantly greater decrease and T concentration a significantly greater increase after ASA treatment, with respect to placebo treatment.

…In fact, after ASA treatment, four volunteers showed individual plasma T concentrations slightly higher than the upper level of the reference range for their age (e.g., 30.67, 30.81, 35.15, and 39.48 nmol/L, respectively) (Fig. 3). 

Reference

As you can see, as with all supplements, there are a lot of interindividual differences. In most of the men it increased their testosterone, but in some, it slightly decreased T. But I’d say that the aspirin wasn’t the cause for the drop in T, because in the placebo group, some also experience slight increases or decreases in testosterone.

I personally use sodium salicylate.

#7 Cistanche

Cistanche is another herb long used by the Chinese to increase kidney yang and improve libido and sexual function.

Some of its properties include, increasing dopamine (lower MAO-B (R)) and DHT (R) and lowers cortisol and serotonin, which helps against stress and improves mood and libido.

Surprisingly, the central 5-HT [serotonin] concentration was downregulated by herb Cistanche decoction treatment (data not shown), because previous research showed that the reduced central 5-HT activity is associated with depression.

Reference

Some of the glycosides in Cistanche are found to be anti-estrogenic, by blocking the estrogen receptors (R).

It’s testosterone boosting properties start all the way from the top, but restoring low kisspeptin 1 levels (R). Kisspeptins are proteins that are ligands of the G-protein coupled receptor, GPR54. Kisspeptin-GPR54 signalling has an important role in initiating secretion of gonadotropin-releasing hormone (GnRH) at puberty. GnRH in turn acts on the anterior pituitary triggering the release of LH, and FSH. Disruption of GPR54 signalling can cause hypogonadotrophic hypogonadism in rodents and humans.

Further down the line it’s been shown to upregulate the expressions of the key steroidogenic enzymes including CYP11A1 and 3β-HSD and also protect the testes from BPA toxicity (R).

Pretty interesting herb. Just make sure you get it from a good quality source, such as Jing herbs, Samsara herbs or LostEmpireHerbs.

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