# Micronutrients in polycystic ovary syndrome: molecular pathways, deficiencies, and therapeutic potential

**Authors:** Madhumitha Natarajan, Shweatha H. E., Raghu Nataraj

PMC · DOI: 10.3389/fendo.2026.1766838 · Frontiers in Endocrinology · 2026-02-10

## TL;DR

This paper explores how micronutrient deficiencies affect PCOS through molecular pathways and suggests targeted supplementation as a potential treatment.

## Contribution

The paper introduces a precision-nutrition strategy for PCOS by linking micronutrient deficiencies to specific molecular pathways.

## Key findings

- Micronutrient deficiencies worsen insulin resistance and inflammation in PCOS via PI3K/Akt and NF-κB pathways.
- Targeted micronutrient supplementation may improve metabolic and reproductive outcomes in PCOS patients.
- Bioavailability and nutrigenomics are critical factors in determining the effectiveness of micronutrient therapy.

## Abstract

Polycystic Ovary Syndrome (PCOS) represents a complex endocrine–metabolic condition which presents with hyperandrogenism and anovulation together with insulin resistance and chronic low-grade inflammation affecting 21% of women during their reproductive years globally. Nutrition has always played a pivotal role in managing PCOS. Emerging evidence demonstrates that micronutrients play an essential part in regulating molecular processes that drive the pathophysiology of PCOS. The deficiency of micronutrients exacerbates insulin resistance, oxidative stress and hormonal dysregulation through their negative impact on PI3K/Akt, NF-κB and Nrf2 and steroidogenic enzyme signaling pathways, all of which play a key role in the pathophysiology of PCOS. This review synthesizes a comprehensive analysis of scientific findings which demonstrate how micronutrient levels influence the regulation of insulin function, inflammatory reactions, oxidative balance, methylation activities and ovarian health in PCOS patients. It also evaluates the potential advantages of targeted micronutrient supplementation used alongside standard management strategies, considering factors such as bioavailability and nutrigenomics, while emphasizing the need for robust large-scale randomized clinical trials. Overall, a molecularly targeted approach to micronutrients represents an emerging precision-nutrition strategy aimed at improving metabolic, reproductive, and inflammatory outcomes in women with PCOS.

## Linked entities

- **Genes:** PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290], AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207], NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790], GABPA (GA binding protein transcription factor subunit alpha) [NCBI Gene 2551]
- **Diseases:** Polycystic Ovary Syndrome (MONDO:0008487)

## Full-text entities

- **Genes:** PTK2B (protein tyrosine kinase 2 beta) [NCBI Gene 2185] {aka CADTK, CAKB, FADK2, FAK2, PKB, PTK}, PRDX5 (peroxiredoxin 5) [NCBI Gene 25824] {aka ACR1, AOEB166, B166, HEL-S-55, PLP, PMP20}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}, GNRH1 (gonadotropin releasing hormone 1) [NCBI Gene 2796] {aka GNRH, GRH, LHRH, LNRH}, CAT (catalase) [NCBI Gene 847], MARCHF8 (membrane associated ring-CH-type finger 8) [NCBI Gene 220972] {aka CMIR, MARCH-VIII, MARCH8, MIR, RNF178, c-MIR}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, HSD3B1 (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1) [NCBI Gene 3283] {aka 3BETAHSD, HSD3B, HSDB3, HSDB3A, SDR11E1}, SLC2A4 (solute carrier family 2 member 4) [NCBI Gene 6517] {aka GLUT4}, SELENOP (selenoprotein P) [NCBI Gene 6414] {aka SELP, SEPP, SEPP1, SeP}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 282306], IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, KEAP1 (kelch like ECH associated protein 1) [NCBI Gene 9817] {aka INrf2, KLHL19}, Slc2a4 (solute carrier family 2 member 4) [NCBI Gene 25139] {aka Glut4}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, Akt1 (AKT serine/threonine kinase 1) [NCBI Gene 24185] {aka Akt}, AMH (anti-Mullerian hormone) [NCBI Gene 268] {aka MIF, MIS}, SHBG (sex hormone binding globulin) [NCBI Gene 6462] {aka ABP, SBP, TEBG}, GCLC (glutamate-cysteine ligase catalytic subunit) [NCBI Gene 2729] {aka CNSHA7, GCL, GCS, GLCL, GLCLC}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, INSR (insulin receptor) [NCBI Gene 3643] {aka CD220, HHF5}, AMHR2 (anti-Mullerian hormone receptor type 2) [NCBI Gene 269] {aka AMHR, MISR2, MISRII, MRII}, TPO (thyroid peroxidase) [NCBI Gene 7173] {aka MSA, TDH2A, TPX}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, VDR (vitamin D receptor) [NCBI Gene 7421] {aka NR1I1, PPP1R163}, AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 497024] {aka NRF2}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 280991] {aka AKT}, Pik3cb (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta) [NCBI Gene 85243], CYP17A1 (cytochrome P450 family 17 subfamily A member 1) [NCBI Gene 1586] {aka CPT7, CYP17, P450C17, S17AH}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, NQO1 (NAD(P)H quinone dehydrogenase 1) [NCBI Gene 1728] {aka DHQU, DIA4, DTD, NMOR1, NMORI, QR1}
- **Diseases:** ovarian dysfunction (MESH:D010049), Magnesium deficiency (MESH:D008275), sleep apnea (MESH:D012891), neuropathies (MESH:D009422), chronic (MESH:D002908), Thyroid dysfunction (MESH:D013959), Type 2 diabetes mellitus (MESH:D003924), depression (MESH:D003866), hyperhomocysteinemia (MESH:D020138), ovulatory dysfunction (MESH:D006331), Chronic low (MESH:D009800), cardiovascular disease (MESH:D002318), infertility (MESH:D007246), endocrine disorder (MESH:D004700), Insulin Resistance (MESH:D007333), anovulation (MESH:D000858), micronutrient abnormalities (MESH:D000014), hyperandrogenism (MESH:D017588), endometrial cancer (MESH:D016889), Nutritional deficiencies (MESH:D044342), hyperinsulinemia (MESH:D006946), Deficiencies (MESH:D007153), PCOS (MESH:D011085), metabolic and reproductive abnormalities (MESH:D060737), metabolic abnormalities (MESH:D008659), obesity (MESH:D009765), Vitamin D deficiency (MESH:D014808), non-alcoholic fatty liver disease (MESH:D065626), anxiety (MESH:D001007), hirsutism (MESH:D006628), B- complex vitamin deficiencies (MESH:D014804), chronic inflammation (MESH:D007249), metabolic syndrome (MESH:D024821), hyperlipidemia (MESH:D006949), dyslipidemia (MESH:D050171), disturbances (MESH:D014832)
- **Chemicals:** 1,25-dihydroxyvitamin D3 (MESH:D002117), vitamin B6 (MESH:D025101), B9 (MESH:C014499), DHT (MESH:D013196), T3 (MESH:D014284), LH (MESH:D007986), Magnesium (MESH:D008274), glucose (MESH:D005947), Calcium (MESH:D002118), Folate (MESH:D005492), ROS (MESH:D017382), steroid hormone (MESH:D013256), pyrimidines (MESH:D011743), cysteine (MESH:D003545), lipid (MESH:D008055), alpha-tocopherol (MESH:D024502), iodine (MESH:D007455), vitamin B12 (MESH:D014805), vitamin D3 (MESH:D002762), Chromium (MESH:D002857), Hcy (MESH:D006710), Se (MESH:D012643), MDA (MESH:D008315), Antioxidant vitamins (-), T4 (MESH:D013974), potassium (MESH:D011188), sodium (MESH:D012964), chromium picolinate (MESH:C030614), progesterone (MESH:D011374), Vitamin C (MESH:D001205), water (MESH:D014867), purines (MESH:D011687), B12 (MESH:C034730), metformin (MESH:D008687), testosterone (MESH:D013739), iron (MESH:D007501), Vitamin A (MESH:D014801), Vitamin E (MESH:D014810), C (MESH:D002244), methionine (MESH:D008715), secosteroid (MESH:D012632), Vitamin D (MESH:D014807), phosphate (MESH:D010710), phosphorus (MESH:D010758), Zinc (MESH:D015032)
- **Species:** Bos taurus (bovine, species) [taxon 9913], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12929159/full.md

## References

61 references — full list in the complete paper: https://tomesphere.com/paper/PMC12929159/full.md

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Source: https://tomesphere.com/paper/PMC12929159