Testosterone Boost via Polyphenolic antioxidants in Aging Men

A group of experts examined the utilization of naturally occurring polyphenolic chemicals to increase testosterone production and shield aging guys against age-related hypogonadism in a recent review that was published in Nutrients.

Context

The growth and maintenance of male sex organs as well as secondary sexual traits depend on androgens, which are mostly produced by Leydig cells in the testes.

Testosterone serves important roles during puberty, such as spermatogenesis and gonadotropin control. It also supports the development of male reproductive organs in the embryo.

Beginning in the thirties, there is a 1% annual fall in testosterone production, which causes late-onset hypogonadism, which is characterized by a decrease in bone density, muscular mass, and libido, among other symptoms.

To determine the effectiveness and safety of polyphenolic compounds as therapeutic agents for preventing late-onset hypogonadism in aging guys, as well as to completely comprehend the mechanisms by which they improve testosterone synthesis, more research is required.

Biosynthesis of testosterone in Leydig cells

The testis’s manufacture of testosterone is carried out by Leydig cells. They also produce dehydroepiandrosterone (DHEA) and androstenedione, yet testosterone is more potent than these hormones at activating the androgen receptor.

The aromatase enzyme (CYP19A1), present in Leydig cells, primarily moderates the production of steroids in these cells by converting small amounts of androgens into estrogens.

Multiple steroidogenic enzymes are required for the biosynthesis of testosterone, with cholesterol serving as the initial substrate. These enzymes include cholesterol side-chain cleavage enzyme (CYP11A1), cytochrome P450 17α-hydroxylase/20-lyase (CYP17A1), 3β-hydroxysteroid dehydrogenase (HSD3B), and 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3).

Acetyl Coenzyme A (acetyl-CoA) can be used to make cholesterol or extracted from plasma by receptor-mediated endocytosis of low-density lipoprotein (LDL) particles. Leydig cells mostly rely on endogenous cholesterol synthesis for testosterone biosynthesis, and they store cholesterol as esters in lipid droplets under normal circumstances.

The first stage of the synthesis of steroids is the translocation of cholesterol into mitochondria, which is made possible by a complex of proteins that includes the translocator protein (TSPO) and the steroidogenic acute regulatory protein (STAR).

Nicotinamide Adenine Dinucleotide Phosphate (NADPH) and ferredoxin reductase enable CYP11A1 inside mitochondria to convert cholesterol to pregnenolone. Next, pregnenolone travels to the smooth endoplasmic reticulum (SER), where HSD3B, CYP17A1, and HSD17B3 continue to convert it to testosterone.

Control of the steroidogenic process

Luteinizing hormone (LH) is the primary regulator of steroidogenesis in Leydig cells. It does this by inducing the Cyclic Adenosine Monophosphate (cAMP)/protein kinase A (PKA) signaling pathway, which in turn affects the expression of steroidogenic enzymes. STAR, which is essential for the transport of cholesterol within mitochondria, and several transcription factors that control the expression of steroidogenic genes are examples of PKA substrates.

This control is also influenced by other signaling pathways, including Janus kinases/signal transducer and activator of transcription proteins (JAK/STAT), Ca2+-calmodulin-dependent protein kinases (CAMK), mitogen-activated protein kinases (MAPK), and protein kinase C (PKC).

Late-onset male hypogonadism development

The hallmark of late-onset male hypogonadism is an aging-related reduction in testosterone production. The standard treatment for this illness is testosterone replacement medication, which can have adverse consequences on the brain and pituitary including diminished spermatogenesis and decreased fertility.

Maintaining muscle mass, bone density, sexual function, energy levels, metabolic health, cognitive function, and general well-being all depend on testosterone.

Men may develop sarcopenia, decreased bone mineral density, decreased libido, erectile dysfunction, weariness, and cognitive decline when their testosterone levels diminish with age. For older men to remain healthy and feel good, their testosterone levels must be kept at a sufficient level.

Organic antioxidants and androgen synthesis

Phenols

Important plant chemicals called flavonoids can be found throughout the plant. They are important for the growth of plants as well as their defense against infections. Anthocyanidins, flavonones, flavones, and flavonols are the different subtypes of flavonoids.

They have been linked to a host of health advantages, including as the prevention of cancer and a decreased risk of neurological and cardiovascular disorders. Celery, thyme, and parsley contain flavones called luteolin and apigenin, which can increase the production of androgen in Leydig cells and induce the expression of steroidogenic genes.

Isoflavones

Soybeans and chickpeas include isoflavones including genistein and daidzein, which can interfere with estrogen signaling in the testis.

Flavonols

Berries, apples, and tea include flavonols like quercetin and myricetin, which improve testicular function and steroidogenesis. When endocrine disruptors are administered to male mice, quercetin raises their testosterone levels. Species-to-species differences may exist in its effects on testosterone production.

Flavanones

Found in grapefruits, flavanones like naringenin can raise serum testosterone levels and stop endocrine disruptors from causing testosterone levels to drop.

Catechins

Male rats’ plasma testosterone levels can be raised by the catechins in tea, red wine, and apples. Green tea polyphenols, however, have been shown in some studies to block the synthesis of androgen.

The anthocyanidins

Berries and grapes contain anthocyanidins, which are recognized for their antibacterial and antioxidant qualities. By suppressing Cyclooxygenase-2 (COX2) and modifying MAPK signaling, they might enhance steroidogenesis.

Derivatives of hydroxycinnamic acid phenethyl ester

In Leydig cells, hydroxycinnamic acids, such as ferulic acid phenethyl ester, can increase androgen synthesis by promoting the expression of genes linked to steroidogenesis.

Gigantol and resveratrol

While resveratrol in red wine and grapes promotes spermatogenesis and the synthesis of testosterone, it can also, under certain circumstances, decrease the synthesis of androgen. Isolated from orchids, gigantol can enhance steroidogenesis and progesterone synthesis in Leydig cells.

In conclusion

To summarize, a diet high in fruits and vegetables can support optimum Leydig cell activity by achieving plasma levels of natural polyphenolic chemicals in the low micromolar range.

The enhancement of Star expression and androgen production by flavonoids with a 5,7-dihydroxychromen-4-one backbone suggests possible synergistic effects on steroidogenesis.

For more information: Prevention of Male Late-Onset Hypogonadism by Natural Polyphenolic Antioxidants, Nutrients,  https://doi.org/10.3390/nu16121815