# Conundrum of Cholesterol Management and Health Implications of Low Cholesterol Levels: A Narrative Review

**Authors:** Subodh Bashyal, Manoj Karki, Deepa Shah

PMC · DOI: 10.31729/jnma.9166 · 2025-07-31

## TL;DR

This paper reviews the risks of excessively lowering cholesterol and emphasizes the need for a balanced approach to cholesterol management.

## Contribution

The paper introduces the 'cholesterol paradox' and highlights the potential health risks of overly aggressive cholesterol reduction.

## Key findings

- Excessively low cholesterol levels may impair cell membrane integrity and neurotransmission.
- Aggressive cholesterol reduction could negatively affect immune function and overall systemic health.

## Abstract

Lowering cholesterol for the health benefit of dyslipidemia is a well-known fact, but emerging evidence highlights risks associated with excessive lowering. The use of lipid-lowering agents to reduce cardiovascular risk is well-established; however, excessive cholesterol reduction has raised concerns about the potential health implications of excessively low cholesterol levels. This review explores the “cholesterol paradox,” highlighting the dual nature of cholesterol as both a contributor to cardiovascular risk and an essential component for cellular integrity, hormone synthesis, brain function, and vitamin D production. A systematic search of PubMed, Google Scholar, JAMA, and Cochrane Library for eligible studies was conducted from 1980 until December 1, 2024. Evidence suggests that excessively low cholesterol levels may impair cell membrane integrity, neurotransmission, and immune function. This review underscores the need for balanced clinical approach to cholesterol management rather than solely aiming for aggressive reduction, ensuring both cardiovascular protection and broader systemic health.

## Linked entities

- **Chemicals:** cholesterol (PubChem CID 5997)
- **Diseases:** dyslipidemia (MONDO:0002525)

## Full-text entities

- **Genes:** LPL (lipoprotein lipase) [NCBI Gene 4023] {aka HDLCQ11, LIPD}, PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465] {aka NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR}, HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) [NCBI Gene 3156] {aka LDLCQ3, LGMDR28, MYPLG}, PCSK9 (proprotein convertase subtilisin/kexin type 9) [NCBI Gene 255738] {aka FH3, FHCL3, HCHOLA3, LDLCQ1, NARC-1, NARC1}
- **Diseases:** body aches (MESH:D010146), dyslipidemia (MESH:D050171), Alzheimer's and Parkinson's disease (MESH:D010300), coronary diseases (MESH:D003327), headache (MESH:D006261), inflammation (MESH:D007249), HYPERLIPIDEMIA (MESH:D006949), abdominal pain (MESH:D015746), hemorrhagic stroke (MESH:D000083302), diabetes (MESH:D003920), Chronic lymphocytic leukaemia (MESH:D015461), endothelial dysfunction (MESH:D014652), gallstones (MESH:D042882), Cancer (MESH:D009369), fatigue (MESH:D005221), diarrhea (MESH:D003967), stroke (MESH:D020521), CHOLESTEROL PARADOX (MESH:D019320), Vitamin D deficiency (MESH:D014808), nausea (MESH:D009325), burn (MESH:D002056), brain stroke (MESH:D001927), death (MESH:D003643), sore throat (MESH:D010612), malnutrition (MESH:D044342), atherosclerosis (MESH:D050197), runny nose (MESH:D000086722), leg cramps (MESH:D009120), vascular defects (MESH:D057772), dizziness (MESH:D004244), digestive dysfunction (MESH:D004066), hypersensitivity reaction (MESH:D006967), acute lymphoblastic leukaemia (MESH:D054218), infection (MESH:D007239), cardiovascular disease (MESH:D002318), ischemic heart disease (MESH:D017202), liver damage (MESH:D056486), muscle injury (MESH:D009135), Coronary artery disease (MESH:D003324), muscle pain (MESH:D063806), cardiac complications (MESH:D006331), CHOLESTEROL (MESH:C535937), bruising (MESH:D003288), rhinitis (MESH:D012220), stomach cramping (MESH:D013272), Hypercholesterolemia (MESH:D006937), Sepsis (MESH:D018805), bloating (MESH:C535647), indigestion (MESH:D004415), necrosis (MESH:D009336), LIPID-LOWERING (MESH:D011017)
- **Chemicals:** Ezetimibe (MESH:D000069438), vitamin D (MESH:D014807), triglyceride (MESH:D014280), 7-dehydrocholesterol (MESH:C016705), phospholipid (MESH:D010743), Cholesterol (MESH:D002784), GABA (MESH:D005680), adrenal and non-adrenal hormones (-), bile acids (MESH:D001647), Niacin (MESH:D009525), cholecalciferol (MESH:D002762), Lipid (MESH:D008055), Fibrates (MESH:D058607), resins (MESH:D012116), steroid hormone (MESH:D013256), creatinine (MESH:D003404), serotonin (MESH:D012701), calcium (MESH:D002118), dopamine (MESH:D004298)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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Source: https://tomesphere.com/paper/PMC12827868