Various foods and nutrients can up- or down-regulate the steroidogenic pathways, resulting in increased or decreased synthesis of steroid hormones. (124) This may occur through a variety of mechanisms, including enzymatic induction or inhibition, and positive or negative feedback mechanisms. (21)(127) There are six major nutrients, botanicals or exogenous hormones that affect steroidogenic hormone levels in humans, including DHEA, pregnenolone, licorice, saw palmetto, Coleus forskohlii, and zinc. Table 1 lists additional ingredients that may affect the steroidogenic pathways.
This diagram represents the steroidogenic pathways.
DHEA
Exogenous DHEA has been used to improve symptoms of aging, physical and psychological well-being, strength and body composition, and sexual function. (103) DHEA may induce or inhibit enzymes involved in regulating the steroidogenic pathways. Specifically, DHEA may induce 17,20 lyase and 5ɑ reductase, while it may also inhibit CYP21, CYP11β1, (117) 3βHSD, and 17βHSD. (19) Administration of oral DHEA increases serum DHEA, (79)(143)(22)(51) DHEA-S, (22)(45)(48)(51)(55)(70)(85)(130)(143) testosterone, (22)(45)(55)(70)(85)(143) androstenedione, (18)(22) estradiol, (45)(51)(55)(85) estrone, (45)(55) and insulin-like growth factor-1 (IGF-1). (45) A study with postmenopausal women showed that supplementation over one year with 25 mg of DHEA increases progesterone, DHT, 17-hydroxyprogesterone, allopregnanolone, beta-endorphin, sexual hormone-binding globulin, LH, FSH, growth hormone, and IGF-1 without affecting endometrial thickness. (34) Evidence of the effect of DHEA on cortisol levels is conflicting as cortisol may either increase, (34)(90) or decrease (35)(117) as a result of DHEA intake. Overall, research supports the use of DHEA to improve cognitive and physical function in older women, (55)(143) and in treating hypoadrenalism, (69) infertility, (11)(97)(109)(137) sexual dysfunction, (93) depression, (94) and atherosclerosis. (73)
Exogenous DHEA has been shown to improve cognitive and physical function in post-menopausal women.
Pregnenolone
Pregnenolone is a precursor to steroid hormones. (135) Administration of pregnenolone or its derivatives may result in the inhibition of CYP11A1, STAR, (68) 17-hydroxylase, 17,20 lyase, (9)(108) and 5ɑ-reductase. (9) Pregnenolone administration has led to increased levels of pregnenolone, allopregnanolone, pregnenolone sulfate, DHEAS, and progesterone. (74) There is evidence that it may also induce CYP3A4. (76)
Pregnenolone is also considered a neurosteroid that increases neuronal activity and may play a major role in neurological conditions. (135) In addition to pregnenolone, other steroids including DHEA, progesterone, and their derivatives can act as neurosteroids and are synthesized by steroidogenic enzymes in the brain. They may regulate gene expression through nuclear receptor binding, modulate neurotransmitter release, and regulate GABA, NMDA, and sigma-1 receptor activities. (138) Pregnenolone, in particular, may improve attention deficits and executive function, (62) as well as working memory (100) and functional capacity (75) in patients with schizophrenia. Additionally, it may be used to treat depressive symptoms in bipolar disorder (17) and improve scores for irritability, lethargy/social withdrawal, and short sensory profile in patients with autism. (32) Evidence exists for its use in treating manic and depressive symptoms in substance-use disorders. (86)
Licorice (Glycyrrhiza glabra)
Licorice has antibacterial, anti-inflammatory, antiviral, antioxidant, and antidiabetic functions. (91) Licorice and its flavonoids mainly act as inhibitors of steroidogenic pathway enzymes, specifically 17,20 lyase, (23) 3βHSD, 11βHSD, (52) 5β, (123) and CYP19. (4) Human trials examining the effects of oral licorice supplementation support its use in alleviating symptoms of menopause including hot flashes, (36)(81) increasing muscle mass, (60) and reducing total fat, visceral fat, and BMI. (6)(71)(125) Licorice administration can decrease testosterone levels (5)(7) and aldosterone, (112) but increase deoxycorticosterone, DHEA, and testosterone. (2) Another study showed that DHEAS decreased in men in response to licorice. (111) Licorice can increase the urinary cortisol/free cortisone quotient. (113) The children of pregnant mothers who had consumed greater than 500 mg per week of glycyrrhizin in licorice during pregnancy also demonstrated higher salivary cortisol concentrations compared with the children of mothers consuming low levels of glycyrrhizin in licorice (less than 250 mg per week). (99) Therefore, high levels of licorice consumption are not recommended during pregnancy due to increased associations with harmful cognitive development in offspring. (98) The consumption of licorice may result in side effects of increased blood pressure, possibly as a consequence of an increased cortisone quotient. (113)
Forskolin (Coleus forskohlii)
Forskolin, a constituent of Coleus forskohlii, may induce many enzymes of the steroidogenic pathways, including STAR, (19) 17-hydroxylase, (101) 3βHSD, (13) 17βHSD, (56) and CYP19. (133) The oral administration of 500 mg (10% extract) per day of forskolin over 12 weeks may weakly increase testosterone levels, but with interindividual variability. (37) Forskolin has also been shown to increase cortisol and DHEA secretion, while increasing 3 beta-HSD and P450c17 expression and activity in human adrenocortical cells. (13) Forskolin can also induce increases in aldosterone. (122) Forskolin may decrease body fat percentage, fat mass and bone mass in conjunction with increased testosterone levels in overweight and obese men. (37) It may also mitigate weight gain in women (40) and treat hypertension. (46)
Saw palmetto (Serenoa repens)
Saw palmetto is well known for its inhibition of 5ɑ-reductase. (87)(136) This may be of particular importance for reducing the conversion of testosterone to DHT, which is linked to benefits seen in treating benign prostatic hyperplasia (BPH) and lower urinary tract symptoms in a similar manner to the pharmaceutical, finasteride. (87) Treatment with saw palmetto has been shown to decrease DHT and epidermal growth factor, and increase testosterone in BPH tissues, suggesting inhibition of 5ɑ-reductase. (25) In vitro studies suggest that saw palmetto’s treatment of BPH may be linked to its inhibition of 5ɑ-reductase. (88)(134) It has been shown to reduce prostate size and improve urinary flow, (104) as well as chronic prostatic inflammation. (64) Saw palmetto extract can also increase average and terminal hair count and thus may have potential in treating male pattern baldness with topical (136) or oral administration. (102) Evidence also suggests that saw palmetto extract can be used in the treatment of prostatitis, (80) sexual dysfunction, (121) and polycystic ovarian syndrome. (15) Doses of up to 960 mg over 18 months have been shown as safe and non-toxic. (8)
Zinc
Zinc has been shown to inhibit 5ɑ-reductase (30)(116)(119) and induce 17-hydroxylase (129) in vitro. In humans, treatment with 10 mg of zinc sulfate (43) or 50 mg of elemental zinc acetate (72) can lead to increased testosterone, DHT levels, and sperm count. (83) Similarly, daily supplementation with 3 mg/kg of body weight of zinc sulfate can prevent decreased testosterone and thyroid hormones associated with exercise in sedentary (58) and athletic men. (59) In male patients with end-stage renal disease on hemodialysis, 250mg per day of supplemental zinc sulfate led to an increase in testosterone and luteinizing hormone. (47) Higher doses of 50 mg three times per day may lead to nausea, vomiting, gastrointestinal cramping, loss of appetite, diarrhea, headaches, lethargy, anemia, and dizziness, (96)(105) while chronic ingestion of greater than 100 mg per day over ten years has been associated with a higher incidence of prostatic cancer. (67)
Additional ingredients that may affect the steroidogenic pathways
The nutrients presented in this table may up-regulate (induce) or down-regulate (inhibit) steroidogenic pathway enzymes, resulting in increased or decreased levels of specific steroid hormones.
Table 1. Natural ingredients that affect the steroidogenic pathways.
The bottom line
Certain nutrients, including DHEA, pregnenolone, licorice, forskolin, saw palmetto, and zinc, have been shown to impact the steroidogenic pathways. These nutrients, which can be found in food and supplements, may induce or inhibit steroidogenic pathway enzymes.