Can Low Iron Cause High Cholesterol?

Iron and cholesterol are essential to human health, playing key roles in oxygen transport, energy production, and cell membrane integrity. While they serve distinct functions, research suggests a possible link between iron levels and cholesterol regulation, raising questions about how deficiencies might impact lipid metabolism.

Understanding this relationship is important for those managing cholesterol levels or addressing iron deficiency. Researchers are investigating whether low iron contributes to elevated cholesterol and the biological mechanisms involved.

Iron’s Role in Lipid Metabolism

Iron influences cholesterol synthesis, transport, and breakdown. As a cofactor for various enzymes, it plays a role in metabolic pathways regulating lipid homeostasis. In the liver, iron affects HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Studies indicate that iron availability can modulate this enzyme’s expression and activity, potentially altering cholesterol production. A deficiency may lead to compensatory changes in lipid metabolism, contributing to dyslipidemia.

Beyond cholesterol synthesis, iron is involved in lipid peroxidation, where free radicals oxidize lipids, impacting their stability and function. Iron’s redox properties make it essential for normal cellular function, but imbalances can lead to oxidative stress, disrupting lipid metabolism. Research in The Journal of Lipid Research suggests iron deficiency may impair lipoprotein turnover, particularly low-density lipoprotein (LDL), which could contribute to altered cholesterol levels. LDL oxidation is a known factor in atherosclerosis development.

Iron also affects mitochondrial function, which is central to fatty acid oxidation. Mitochondria rely on iron-containing enzymes such as acyl-CoA dehydrogenases. When iron is insufficient, mitochondrial efficiency declines, disrupting lipid utilization and storage. This can lead to lipid accumulation in the liver, observed in conditions like non-alcoholic fatty liver disease (NAFLD). A study in Hepatology found that individuals with iron deficiency anemia exhibited altered lipid profiles, including increased triglyceride levels, indicating broader metabolic effects.

Potential Mechanisms Linking Low Iron and Elevated Cholesterol

Iron deficiency has been associated with disruptions in lipid metabolism, and several pathways may explain how inadequate iron contributes to elevated cholesterol. One mechanism involves hepatic cholesterol synthesis. Iron modulates sterol regulatory element-binding proteins (SREBPs), transcription factors controlling cholesterol and fatty acid biosynthesis. Under normal conditions, iron helps regulate SREBP activation, ensuring balanced cholesterol production. When iron levels are low, SREBP activity may become dysregulated, leading to increased cholesterol synthesis.

Iron deficiency also affects cholesterol transport and clearance. The liver relies on iron-containing enzymes to convert cholesterol into bile acids, a primary route for cholesterol excretion. A reduction in iron-dependent enzymes such as cholesterol 7 alpha-hydroxylase (CYP7A1) can impair bile acid synthesis, leading to inefficient cholesterol elimination. This may cause cholesterol accumulation in the bloodstream, raising LDL levels. Clinical research in Arteriosclerosis, Thrombosis, and Vascular Biology has reported that individuals with iron deficiency anemia often exhibit higher LDL cholesterol, supporting the idea that insufficient iron impairs cholesterol clearance.

Mitochondrial dysfunction further complicates the relationship between iron and cholesterol. Iron is a necessary cofactor for mitochondrial enzymes involved in fatty acid oxidation and energy metabolism. A deficiency compromises mitochondrial efficiency, shifting metabolism toward lipid storage rather than utilization. This can lead to hepatic lipid accumulation and altered cholesterol homeostasis. A study in Metabolism: Clinical and Experimental found that patients with iron deficiency exhibited increased hepatic lipid deposition, correlating with higher serum cholesterol levels. This suggests disturbances in mitochondrial function due to iron deficiency contribute to metabolic dysregulation.

Key Biomarkers for Assessing Iron and Cholesterol

Evaluating iron and cholesterol levels requires biomarkers reflecting storage, transport, and metabolic activity. Serum ferritin is a key measure of iron status, representing the body’s iron reserves. Low ferritin levels indicate depleted iron stores, even before anemia develops. However, as an acute-phase reactant, ferritin can be elevated by inflammation or infection, potentially masking deficiency. To account for this, clinicians often assess transferrin saturation, which measures the percentage of iron bound to transferrin, the primary transport protein. A transferrin saturation below 20% generally indicates iron deficiency, while levels above 50% may signal iron overload, both of which can affect metabolism.

Lipid panels provide a comprehensive view of cholesterol status. Total cholesterol, LDL, high-density lipoprotein (HDL), and triglycerides each offer insights into lipid transport and storage. Elevated LDL is linked to increased cardiovascular risk, while low HDL may indicate impaired reverse cholesterol transport. Triglycerides can be influenced by metabolic shifts related to iron availability. Research in Clinical Chemistry has shown that individuals with iron deficiency anemia often exhibit altered lipid profiles, including elevated triglycerides, reflecting disruptions in lipid mobilization and utilization.

The interplay between iron and cholesterol metabolism also involves enzymatic and transport markers. Hepcidin, a hormone regulating iron absorption and distribution, provides insight into iron availability. Suppressed hepcidin levels are common in iron deficiency, leading to increased intestinal iron absorption, whereas elevated levels can indicate iron sequestration or inflammation. Additionally, apolipoproteins such as ApoB and ApoA1, which are responsible for lipoprotein transport, offer a more precise assessment of lipid metabolism than traditional cholesterol measurements. ApoB, associated with LDL particles, serves as a marker of atherogenic risk, while ApoA1 reflects HDL functionality in cholesterol efflux.