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Herbs and Nutrients That May Assist
Liquorice
Glycyrrhiza glabra, root dry
White Peony
Paeonia lactiflora, root dry
Inositol
Chromium
Chromium chloride hexahydrate
Folic acid
Actions
- Reduces abnormal androgen production
- Improves insulin resistance
- Promotes healthy oocyte development
Clinical Applications
-
Polycystic ovarian syndrome
- Improves hormonal dysfunction
- Reduces hirsutism and acne
- Reduces metabolic dysfunction
- Enhances ovulation and cycle regularity
- Supports fertility and assisted reproductive technology outcomes
Clinical Overview
Polycystic ovarian syndrome (PCOS) is a complex disorder involving excess androgen activity, arrested ovulation and insulin resistance (IR) (Figure 1). [1] These factors collectively perpetuate overproduction of testosterone within ovarian theca cells, which sustains hormonal and metabolic dysregulation in PCOS. [2] Botanical extracts liquorice and white peony have been shown to decrease abnormal androgen production [3] and improve aberrant metabolic patterns. [4],[5] Further, human clinical trials indicate the benefits of myo-inositol, folic acid and chromium for the treatment PCOS-related IR [6],[7] and hirsutism, [8],[9] supporting menstrual cycle regularity, [10] ovulation, [11] and enhanced fertility outcomes in conjunction with assisted reproductive technology (ART). [12] By addressing the drivers of PCOS, these therapies promote hormonal and metabolic wellbeing.
Figure 1: Clinical features commonly seen in PCOS. [13]
Background Information
PCOS is associated with reproductive abnormalities caused by hormonal and metabolic disturbances, including hyperandrogenism (HA) and IR. [14] Clinical diagnosis of PCOS is determined by the presence of at least two of the following features:
- Biochemical HA [15];
- Ovulatory dysfunction (OD) [16]; and
- Polycystic ovarian morphology (PCOM). [17]
With a global prevalence of 6% to 11%, [18] PCOS is the leading cause of infertility in reproductive-aged women. [19] Clinical manifestations of PCOS can include HA-related symptoms such as hirsutism (male-pattern hair growth in women) and acne. [20] Further, in pregnancy, the syndrome is associated with an increased risk of complications, such as gestational diabetes and pre-eclampsia. [21] Moreover, women diagnosed with PCOS have an increased risk of major depression, panic disorder and generalised anxiety disorder, [22] adding to the complexity of patient care.
The aetiology of PCOS is multifactorial and involves interactions between genetic, metabolic, foetal, and environmental influences. [23] While these individual factors can vary amongst patients, the presence of HA and IR is common, and strongly contributes to the condition’s pathophysiology. [24],[25] For instance, in animal models, HA has been shown to cause the same reproductive, endocrine and metabolic features seen in PCOS. [26] In addition, treatments that lower androgen activity in women diagnosed with the syndrome restore both menstrual regularity and ovulation. [27] Interestingly, research indicates that IR is associated with elevated androgens and PCOS irrespective of body mass index (BMI). [28] In individuals with IR, use of insulin-sensitising interventions has led to the successful management of clinical symptoms, in addition to reducing OD and decreasing testosterone production by 20%. [29] As such, addressing both HA and IR are fundamental in supporting treatment outcomes in PCOS.
Androgens and Insulin in PCOS
In healthy women, the adrenal glands and the ovaries produce androgens in response to adrenocorticotropic hormone (ACTH) and luteinizing hormone (LH) respectively. [30] In approximately 30% to 50% of individuals with PCOS, the adrenal gland contributes to total androgens due to enhanced responses to ACTH. [31] However, ovarian theca cells are the main source of excess androgen production in PCOS, occurring in response to increased LH stimulation and hyperinsulinemia. [32] Various steroid hormones and enzymes contribute to androgen activity in PCOS, including:
- Testosterone (T) [33];
- Androstenedione (A4) [34]; and
- Dehydroepiandrosterone sulfate (DHEA-S). [35]
These androgenic compounds perpetuate HA by increasing the pulsatile release of LH via neuroendocrine pathways. [36] Specifically, elevated androgen activity in the body stimulates gonadotropin-releasing hormone (GnRH) neurons in the brain, leading to greater GnRH-mediated LH pulsatility, [37] which upregulates androgen synthesis in the ovary (Figure 2). [38] This subsequently increases the ratio of LH to follicle-stimulating hormone (FSH). [39] FSH normally minimises T levels by enhancing ovarian aromatase (CYP19A1), which converts locally produced T into estradiol (E2); therefore, reduced FSH relative to LH increases androgen synthesis. [40],[41] As such, excess LH activity leads to a state of tissue HA. [42]
Figure 2: Influence of androgens in PCOS. [43],[44]
Key: AMH: Anti-Müllerian hormone, GnRH: Gonadotropin-releasing hormone, LH: Luteinizing hormone, FSH: Follicle-stimulating hormone, SHBG: Sex hormone binding globulin, AR: Androgen receptor.
This cascade of events is associated with PCOM features. For example, elevated androgens stimulate the growth of small antral follicles [45] (2 mm to 6 mm in diameter) [46] in the ovary, while simultaneously inhibiting follicular development and maturation. This causes arrested follicle growth, anovulation (due to impaired follicle maturation) and abnormal ovarian morphology featuring many small follicles. [47] Further, small antral follicles amplify LH signalling through the greater presence of Anti-Müllerian hormone (AMH), which is predominantly produced by ovarian follicles up to 7 mm in diameter. [48] This, in turn, stimulates GnRH-dependant LH secretion, [49] further potentiating excess androgen activity in PCOS.
Beyond these effects, HA states also contribute to metabolic dysfunction by increasing fat deposition, enlarging adipocyte cells, and reducing adiponectin, a fat-derived hormone involved in glucose regulation and fatty acid oxidation. [50] These changes are strong predictors of IR, [51] which exacerbates PCOS pathophysiology. [52]
In a healthy state, insulin binds to insulin receptors, generating a cascade of signals that promote the cellular uptake and metabolism of glucose. [53] In IR, however, insulin signalling is disturbed and cells no longer respond appropriately to circulating insulin. [54] This results in elevated insulin levels (hyperinsulinemia) produced by the pancreas in an attempt to restore glucose homeostasis and overcome IR. [55]
Hyperinsulinemia intensifies androgen activity through two mechanisms (Figure 2), including:
- Stimulation of LH secretion via GnRH, thus amplifying LH-mediated androgen production [56],[57]; and
- Inhibiting hepatic synthesis of sex hormone binding globulin (SHBG), which normally binds to and inactivates circulating androgens, resulting in a greater serum concentration of free androgens. [58]
In addition to this, several inflammatory mediators have been linked to increased IR, including tumour necrosis factor alpha (TNF-α), [59] inflammatory protein kinases, including c-JUN N-terminal kinase (JNK), [60] nuclear factor kappa B(NFκB), [61] and diet-induced inflammation (associated with excess proinflammatory fatty acids and reduced anti-inflammatory omega-3 fatty acid intake). [62] Collectively, these inflammatory mediators, alongside physiological adipocyte overexpansion (associated with excess caloric intake [63] and HA [64]), cause inflammation in fatty tissue through the activation of hypoxia-inducible factor 1 (HIF-1) genes, resulting in IR within adipocytes. [65] These effects increase hormone-sensitive lipase (HSL) activity, which stimulates the breakdown of fatty tissue, thereby increasing serum levels of free fatty acids (FFA), which deposit in the liver and skeletal muscle, leading to IR within these tissues. [66] Higher levels of inflammation have been observed in PCOS women compared to healthy controls,[67] which indicates that lowering inflammation is important aspect of IR treatment in this patient population.
HA and IR are interdependent factors within PCOS pathophysiology, which directly perpetuate its inherent complexity. [68] However, causes of inflammation such as dysbiosis of gut microbiota [69] and exposure to environmental toxins such as bisphenol A (BPA) [70] have also been linked to PCOS phenotypes, indicating that inflammation is a third interdependent factor in its pathophysiology. Therefore, an approach that addresses hormonal, metabolic and inflammatory issues is necessary for achieving successful treatment outcomes in PCOS.
Actions
Reduces Abnormal Androgen Production
Liquorice has traditionally been used for female infertility, and has been found to reduce androgen synthesis and serum T levels in women. [71] Constituents of liquorice limit the activity of enzymes that contribute to androgen synthesis (Figure 3). For example, glycyrrhetinic acid reduces the conversion of A4 to T by inhibiting 17-beta-hydroxysteroid dehydrogenase (17β-HSD) activity in rat ovarian tissue in vitro. [72] Moreover, an in vitro study revealed that liquorice constituent, isoliquiritgenin, effectively reduces mRNA expression of CYP17A1 enzymes, which catalyse the formation of A4 and DHEA within ovarian antral follicles, and therefore may limit downstream A4 and T synthesis mediated by 17β-HSD. [73]
Figure 3: Major pathways involved in androgen biosynthesis. [74]
Key: CYP11A: cholesterol desmolase, CYP17A1:17 alpha-hydroxylase/17,20 lyase, 3B HSD: 3 beta-hydroxysteroid dehydrogenase, 17B HSD: 17 beta-hydroxysteroid dehydrogenase, CYP19A1: Aromatase.
Similarly, paeoniflorin, a key constituent of white peony, also limits enzymatic activation of androgens as demonstrated by a 2019 study in murine theca cells. [75] Ovarian tissue treated with corticosteroids resulted in elevated T secretion (p<0.05), which was reversed by white peony extract (WPE) standardised to contain 70% paeoniflorin. [76] Researchers also found that WPE decreased the expression of steroidogenic enzymes, including CYP17A1 and CYP11A1, which lie upstream of androgen synthesis. By limiting the activity of enzymes that contribute to androgen steroidogenesis, white peony may mitigate hyperandrogenic follicular environments in PCOS. [77]
In combination, liquorice and white peony have been shown to effectively lower T production in animal models [78],[79]; interestingly, this was only observed in ovarian tissue, and not adrenal tissue. [80] In addition, liquorice and white peony did not significantly affect serum LH or FSH levels, suggesting that their T-lowering effects are not mediated by neuroendocrine mechanisms. From these results, researchers postulated that the herbs inhibit enzymes involved in A4 to T conversion, or potentially up-regulate aromatase-mediated conversion of T to E2. [81]
Improves Insulin Resistance
Animal studies indicate that administration of liquorice constituents attenuates IR through multiple mechanisms. [82] , [83] Specifically, glycyrrhizin, was shown to reduce elevated blood glucose, insulin, blood lipids and inflammatory byproducts of IR through the activation of peroxisome proliferator activated receptor gamma (PPAR-γ) and glucose transporter four (GLUT4) proteins. This led to improved fatty acid oxidation and glucose uptake in skeletal muscle, thereby enhancing metabolism and removal of excess FFA and glucose from the bloodstream. [84] In addition, liquorice constituent, glycyrrhizic acid, administered to obese rats over 28 days, effectively decreased tissue lipid deposition associated with IR by raising tissue lipoprotein lipase (a PPAR-regulated enzyme), and thus enhanced insulin sensitivity through increasing fatty acid metabolism. [85]
Further to this, white peony has been shown to moderate inflammation-induced IR in adipocytes. [86] When treated with paeoniflorin, insulin-stimulated glucose uptake was restored in isolated human adipocytes through attenuating levels of IR-inducing adipokine, TNF-α. In addition, paeoniflorin reduced interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) associated with chronic, low-grade inflammation implicated in the development of IR in adipose cells. [87]
Inositol is a glucose isomer largely produced by the kidneys, and serves as a structural basis for cellular membranes and inositol phosphates, which are important secondary messengers in glucose metabolism, involved in healthy insulin activity. [88] Intracellularly, inositol is incorporated into two inositol phosphoglycans (IPG); IPG-A contains myo-inositol (MYO), and IPG-P contains D-chiro-inositol (DCI) (Figure 4), which both display strong insulin-mimicking actions shown to reduce hyperglycemia [89] and inhibit lipolysis. [90] Research suggests that both forms of inositol work synergistically in healthy glucose metabolism. [91] For instance, DCI is a central compound within insulin second messenger 2 (INS-2), an intracellular messenger that activates mitochondrial pyruvate dehydrogenase, and promotes the oxidation and metabolism of glucose. [92] In contrast, MYO increases cellular sensitivity to glucose independent of insulin by enhancing GLUT4 translocation to plasma membranes, thereby assisting cellular glucose uptake. [93]
Figure 4: Conversion of myo-inositol (MYO) into myo-inositol phosphoglycans (MYO-IPG-A), D-chiro inositol (DCI) and D-chiro inositol phosphoglycans (DCI-IPG-P). [94],[95]
Normally, MYO is converted into DCI via epimerase enzymes, which is then incorporated into IPG-P and stored in cellular membranes until they are liberated by phospholipase enzymes (Figure 4). [96] This process in a healthy individual is facilitated by insulin; however, in insulin resistant tissues, MYO to DCI conversion is severely reduced, limiting IPG-P and therefore impairing glucose metabolism. [97] In theory, therefore, improving insulin activity should restore inositol-mediated functions, however, in PCOS, D-chiro inositol phosphoglycans (DCI-IPG-P) were shown to be unresponsive to insulin stimulation. [98] This suggests that other factors beyond insulin influence IPG-P levels, such as reduced MYO availability.
Data indicates that MYO deficiency is associated with hyperglycemia, [99] which is linked to other metabolic features seen in PCOS, such as hyperinsulinemia and reduced SHBG. [100] Moreover, in a recent survey, 19.6% of Australian women were shown to have diabetes or impaired glucose tolerance, both conditions associated with hyperglycaemia, and may therefore be suffering from MYO deficiency due to the following mechanism. [101] In hyperglycemic states the kidneys excrete glucose in an attempt to protect the body from excess glucose exposure, and due to its glucose-like structure, MYO is also excreted. [102] As a result, inositol levels are compromised, leading to intracellular MYO depletion and reduced DCI levels, potentiating IR. [103] Research indicates MYO supplementation enhances insulin communication in PCOS, supporting the role of MYO repletion in reversing IR. [104],[105]
Chromium has been shown to enhance insulin sensitivity in IR. [106] Data from animal models indicates that chromium potentiates insulin signaling, blunts inflammatory mediators that contribute to IR, attenuates oxidative stress, and boosts intracellular 5’adenosine monophosphate-activated kinase (AMPK) that promotes fatty acid oxidation. [107] These effects of chromium, together with its low-risk profile, support its use in IR management. [108] Moreover, folic acid supplementation appears to raise insulin sensitivity through its role as a nutritional cofactor in DNA methylation. [109] In a murine model, folic acid induced beneficial changes in DNA methylation and the expression of genes related to obesity and insulin secretion and was also associated with improved IR and decreased fat mass. [110] Further to this, folate deficiency was linked to glucose intolerance and IR in mice fed a folate-deficient diet over 16 weeks,[111] underscoring the importance of adequate folate intake in IR.
Promotes Healthy Oocyte Development
In addition to its role in insulin communication, inositol supports healthy oocyte development by facilitating intracellular calcium release in ovarian tissue. This process plays an important role in oocyte maturation, fertilisation and embryo development, particularly in the final stages of oocyte progression. [112] Inositol is an important component of intracellular second messenger, inositol-1,3,4-triphosphate (InsP3). During the luteal phase, a surge in LH indirectly activates the binding of InsP3 to calcium ion channels, triggering the release of stored calcium from the smooth endoplasmic reticulum into the cytosol. [113] The integral role of inositol in intracellular calcium release highlights the importance of adequate inositol availability in oocyte development.
In PCOS patients, ratios of MYO to DCI within follicular fluid are significantly lower compared to healthy participants (0.2:1 vs. 100:1). [114] Moreover, MYO supplementation enhances oocyte quality and promotes the success of embryo transfer. [115] MYO has also been associated with increased expression of genes, GK 1, RGS2 and CDC42, which play a role in enhancing oocyte energy synthesis, preventing premature intracellular calcium release (and therefore immature oocyte release), and fostering oocyte development, respectively. [116] As such, inositol supports several pathways involved in oocyte development, ovulation and reproductive health.
Clinical Applications
Polycystic Ovarian Syndrome
Improves Hormonal Dysfunction
Several natural compounds address the HA, abnormal LH activity and subsequent IR associated with PCOS. For instance, in healthy women liquorice was shown to reduce serum T (27.8±8.2 to 17.5±6.4 ng/dL, p<0.05) when administered at a dose of 3.5 g/d during the luteal phase of two consecutive menstrual cycles. [117] Comparably, data supports both inositol and folic acid in lowering serum androgens. [118] Results from 30 PCOS patients receiving a combination of MYO (4 g/d) and folic acid (400 µg/d) over 12 weeks revealed a reduction in serum T (1.4±4.2 to 0.7±1.4 nmol/L, p<0.001). In addition to this, the same combination of MYO and folic acid given to 25 women with PCOS, and was demonstrated to lower LH, total T, A4 and DHEA-S (p<0.05), highlighting the effectiveness of specific herbs and nutrients in lowering androgen activity in PCOS patients. [119]
Further to this, inositol and folic acid limit LH activity and IR in PCOS. In a randomised clinical trial conducted in 50 overweight PCOS women, subjects received 2 g/d of MYO combined with 200 µg/d of folic acid (group A), or 400 µg/d of folic acid alone (group B), over 12 weeks prior to undergoing an in vitro fertilisation (IVF) cycle. [120] Participants were assessed for changes in plasma LH, FSH and insulin. In group A, significant reductions in LH and LH:FSH ratios were observed (p<0.005) compared to group B. Moreover, group A also experienced a reduction in insulin levels (11.4±2.2 vs. 5.5±1.1 µU/mL, p<0.005) and enhanced insulin sensitivity as demonstrated by a reduction in homeostatic model assessment of IR (HOMA-IR) values (2.5±0.6 compared with 1.1±0.3, p<0.01). Further, inositol has been shown to significantly improve LH:FSH ratios, and lower serum A4 independent of its effects on insulin sensitivity (p<0.05), supporting the therapeutic value of inositol in this population group. [121]
Reduces Hirsutism and Acne
Elevated androgens are associated with hirsutism in 70% of women who experience male-pattern hair growth. [122] Additionally, symptoms of HA are also associated with acne [123]; however, its aetiology involves a variety of factors outside of androgen excess. [124] Evidence supports the effects of inositol and folic acid in reducing HA-associated hirsutism in PCOS. Over 12 weeks, 30 female patients supplementing MYO (4 g/d) and folic acid (400 µg/d) experienced a reduction in Ferriman-Gallwey (mFG)[*] scores (p<0.01) in association with reduced T levels (p<0.03). [125] Further to this, in 46 women with mild to moderate hirsutism, 4 g/d of MYO in addition to 400 µg/d of folic acid over six months led to a significant reduction in mFG scores compared to baseline (p<0.001), also associated with reduced serum T levels (p<0.002) (Figure 5). [126]
Figure 5: Effect of 4 g/d of MYO and 400 µg/d of folic acid in HA-associated hirsutism over six months. [127]
Moreover, chromium displays favourable effects on HA-associated symptoms. In a study of 30 PCOS patients supplementing 200 µg/d of chromium picolinate over eight weeks, participants experienced a significant reduction in mFG scores (p<0.002) and acne (p<0.04) compared to placebo, demonstrating the beneficial effects of this nutrient in hirsutism and acne. [128]
Reduces Metabolic Dysfunction
Inositol and folic acid have also been associated with positive changes in metabolic health in PCOS patients. Fifty women with IR or hyperinsulinemia were randomised to receive either insulin-sensitising medication, metformin, or MYO at a dose of 4 g/d combined with folic acid at 400 µg/d, over six months. [129] Researchers assessed participants for changes in insulin secretion, HOMA-IR, serum androgens and menstrual cycle length. MYO and folic acid were found to be as efficacious as metformin in lowering IR (p<0.05) and hyperinsulinemia (p<0.01), and were also correlated with reduced serum androgens and improved menstrual cycle regularity (p<0.05). Further, in 42 obese PCOS patients, MYO (4 g/d) and folic acid (400 µg/d) administered for eight weeks was associated with reductions in hyperinsulinemia and BMI. [130] Subjects were divided into two groups based on their baseline fasting plasma insulin levels: group A (insulin <2 µU/ml, n=15) and group B (insulin >12 µU/ml, n=27) to determine the effects of treatment on metabolic health. Improvements in fasting insulin levels and BMI were correlated with advanced hyperinsulinemic states (i.e. insulin >12 µU/ml, p<0.04), indicating that positive changes in metabolic status were related to the degree of IR. Together, this data supports the efficacy of inositol and folic acid in metabolic dysfunction.
Chromium also supports markers of metabolic health. A meta-analysis and systematic review of seven studies involving 198 PCOS patients found that chromium decreased BMI, free T and fasting insulin. [131] In another study, PCOS patients supplementing 200 µg/d of elemental chromium for eight weeks experienced a significant reduction in fasting insulin, HOMA-IR, serum triglycerides and total cholesterol. [132] Further, in a study of 92 PCOS patients, those receiving 200 µg/d of chromium picolinate demonstrated similar benefits in fasting insulin and insulin sensitivity to patients receiving 1.5 g/d of metformin. [133]
OD is a key diagnostic feature of PCOS. [134] In a normal ovarian luteal phase, the event of ovulation is characterised by a sharp elevation in LH activity relative to FSH, followed by the release of a fully matured oocyte alongside rising serum progesterone concentrations. However, even when ovulation occurs in PCOS, subnormal progesterone concentrations have been observed, indicating suboptimal follicular maturation and OD. [135]
Enhances Ovulation and Cycle Regularity
Inositol and folic acid increase ovulation frequency in PCOS, as evidenced by improved luteal phase activity and normal progesterone concentrations. [136] Ninety-two PCOS patients with oligomenorrhoea or amenorrhea receiving MYO (4 g/d) and folic acid (400 µg/d) or a placebo for 14 weeks were evaluated for ovulation frequency and luteal activity. MYO and folic acid were shown to increase ovulation frequency (determined by adequate serum progesterone and normal LH levels) compared to the placebo group (p<0.001). Specifically, women in the treatment group experienced greater ovulation frequency across 14 weeks (two and four ovulations), compared to lower rates in the placebo group (between zero and one ovulations). In addition, active treatment was also associated with a reduction in days until first ovulation (24.5 days, compared to 40.5 days). Moreover, the same combination of MYO and folic acid in 25 PCOS women supplemented over six months was shown to reduce mean cycle length from 93±60 to 57±50 days (p<0.001). [137] In this study, 44% of women experienced improvements in cycle length, indicating the benefits of enhanced intake of key nutrients on reproductive health in PCOS.
Supports Fertility and Assisted Reproductive Technology Outcomes
Research supports the combined use of inositol and folic acid in enhancing ART outcomes. These nutrients are associated with significant improvements in oocyte size and quality, [138],[139] ovulation rates [140] and pregnancy rates, [141],[142] as well as a reduction in the dose and duration of exogenous recombinant FSH treatment (rFSH) administered as part of ovarian hyperstimulation protocols. [143],[144] For example, MYO (2 g/d) and folic acid (200 µg/d) supplemented in 25 PCOS women resulted in 82% of oocytes being of the highest quality level, compared to 36% in the folic acid group (p<0.05). [145] The treatment group also displayed a greater number of follicles >16 mm (p<0.03), which is associated with better ART outcomes. [146] Additionally, MYO and folic acid increased the number of clinical pregnancies carried to term (p<0.05) and reduced the dose and duration (p<0.002) of rFSH units required to achieve ovulation. [147]
Similarly, in 34 infertile PCOS patients receiving either MYO (4 g/d) plus folic acid (400 µg/d), or folic acid alone (400 µg/d), follicle size and quality was enhanced in the inositol group (p<0.05). [148] Further, the same doses of MYO and folic acid in 86 PCOS patients over 12 weeks significantly increased day 21 (mid luteal) serum progesterone (p<0.01) compared to folic acid alone, indicating better ovulatory function. Additionally, MYO and folic acid resulted in more pregnancies (p<0.02) and lowered the dose and duration of rFSH required for ovulation to occur (p<0.03). [149] In another study conducted in 26 women with PCOS, eight weeks of MYO and folic acid supplementation (1,200 mg/d and 200 µg/d respectively) prior to clomiphene citrate (CC)-induced ovulation resulted in higher ovulation rates compared to infertile women receiving CC alone (p<0.0001), [150] substantiating the use of inositol and folic acid in infertile PCOS patients.
Safety Information
Disclaimer: In the interest of supporting health Practitioners, all safety information provided at the time of publishing (October 2025) has been checked against authoritative sources. Please note that not all interactions have been listed.
For further information on specific interactions with health conditions and medications, refer to clinical support on 1800 777 648(AU), anz_clinicalsupport@metagenics.com, or via Live Chat www.metagenics.com.au
Pregnancy
- Avoid use. Liquorice is unlikely to cause adverse effects if used for preconception and in the early weeks of pregnancy. However, liquorice should be discontinued once pregnancy is confirmed. Two studies have shown that high glycyrrhizin intake during pregnancy significantly increased the likelihood of early delivery, although did not affect birth weight or maternal blood pressure. Additionally, children who were exposed to high glycyrrhizin exposure prenatally (≥500 mg/week) experienced changes to cognitive and psychiatric development. Therefore, it is recommended to avoid the use of liquorice during pregnancy.
Breastfeeding
Appropriate for use
Prescribing Tips and Notes
Dosing of folate
- In healthy patients, supplemental doses of 1,000 µg/d are considered safe and beneficial.
- Use of higher supplemental doses >1,000 µg/d, should be limited to a three-month period.
- Always use with methylating cofactors such as B6 and B12, to support normal physiological use of folate derivatives, and avoid potential masking of B12 deficiency.
Contraindications
-
Digoxin: Due to the effects of liquorice in combination with digoxin, monitor patients and avoid long-term use.
- Due to the potassium-decreasing activity of liquorice, the combination of liquorice with digoxin may increase the risk of cardiac/digitalis toxicity due to potassium loss.
- This cardiac glycoside drug is metabolised by cytochrome P450 3A4 and has a narrow therapeutic range.
- Diuretics: Due to the potassium-decreasing activity of liquorice, the combination of liquorice with diuretics (including loop, thiazide and potassium-depleting) may compound diuretic-induced potassium loss, thus increasing the risk of hypokalaemia. Avoid long-term use (e.g. more than two weeks) and monitor potassium levels in patients taking diuretic drugs.
- Heart disease: The mineralocorticoid effects of liquorice can worsen congestive heart failure and fluid retention, as well as increase the risk of arrhythmias, therefore avoid use in patients with heart disease.
- Hypokalaemia: The mineralocorticoid effects of liquorice can decrease serum potassium levels and exacerbate hypokalaemia, therefore avoid use in patients with this condition.
- Severe renal (kidney) disease/insufficiency: The mineralocorticoid effects of liquorice may worsen renal function. Avoid use in patients with severe kidney insufficiency/renal disease.
Cautions
- Anticoagulant / antiplatelet drugs: Theoretically, combining peony with anticoagulant or antiplatelet drugs might increase the risk of bleeding.
- Antidiabetic drugs: Theoretically, chromium and insitol may have additive effects with antidiabetic agents and increase the risk of hypoglycaemia.
- Antihypertensive medication: Theoretically, liquorice might reduce the effects of antihypertensive drugs.
- Chemotherapy drugs (Paclitaxel and Cisplatin): Theoretically, liquorice might reduce the effects of certain chemotherapy.
- Corticosteroids: Theoretically, concomitant use of liquorice and corticosteroids might increase the side effects of corticosteroids, as liquorice may increase potassium loss and increase the risk of potassium depletion. Use with caution in patients on acute or chronic corticosteroid therapy.
- Clozapine (Antipsychotic): Theoretically, peony might increase the levels and clinical effects of clozapine.
- Contraceptive drugs: Theoretically, peony might interfere with contraceptive drugs due to competition for oestrogen receptors.
- Cytochrome P450 (CYP) CYP1A2, CYP2B6, CYP2C19, CYP2C8, CYP2C9, CYP3A4 substrates: Theoretically, liquorice and/or peony might increase levels of drugs metabolised by these CYP enzymes.
- Insulin: Theoretically, concomitant use of chromium and insulin might increase the risk of hypoglycaemia.
- Levothyroxine: Chromium might bind levothyroxine in the intestinal tract and decrease levothyroxine absorption.
- Methotrexate: Folic acid might reduce the efficacy of methotrexate as a cancer treatment when given concurrently.
- Midazolam (Benzodiazepine): Theoretically, liquorice might decrease levels of midazolam.
- Oestrogens: Theoretically, liquorice might increase or decrease the effects of oestrogen therapy.
- Phenylbarbitol: Folic acid might have antagonistic effects on phenobarbital and increase the risk for seizures.
- Phenytoin: Folic acid and peony might reduce serum levels of phenytoin in some patients.
- Pyrimethamine: (Antiparasitic medication for toxoplasmosis infections): Folic acid might antagonize the effects of pyrimethamine.
- Warfarin: Theoretically, liquorice might decrease plasma levels and clinical effects of warfarin.
- Hypertension: The mineralocorticoid effects of liquorice can increase blood pressure. [173] Use with caution in patients with hypertension, and not for prolonged periods (e.g. more than two weeks). [174]
Footnotes
[*] mFG involves visual assessment of nine body areas for terminal hair growth. A cumulative score of three to five is associated with HA
References
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[6] Fruzzetti F, Perini D, Russo M, Bucci F, Gadducci A. Comparison of two insulin sensitizers, metformin and myo-inositol, in women with polycystic ovary syndrome (PCOS). Gynecol Endocrinol. 2017 Jan;33(1):39-42. doi: 10.1080/09513590.2016.1236078.
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