High linoleic acid intake during pregnancy may harm fetal growth and raise obesity risk

Sep 10 2024

New research reveals potential dangers of common dietary fats during pregnancy, highlighting the need for balanced nutrition to protect future generations.

Review: Effect of a High Linoleic Acid Diet on Pregnant Women and Their Offspring. Image Credit: Bulgn / Shutterstock

A recent study by researchers in Australia, published in the journal Nutrients, reviewed the effects of high maternal dietary intake of linoleic acid (LA) in pregnancy on birth outcomes, inflammation, and obesity.

Nutritional intake in pregnancy influences gestation, fetal weight and length, and offspring development. Excess or deficient maternal nutrition in pregnancy may adversely affect offspring’s health and elevate the risk of chronic diseases later in life.

A balanced diet is necessary to support healthy placental development, fetal needs, and the increased requirements related to maternal adaptation to pregnancy.

Amino acids and glucose are the primary nutrients required by the fetus. Inadequate levels of micronutrients and macronutrients, such as folate, thiamine, vitamins, iron, and fats, may predispose the offspring to chronic conditions.

Fatty acids (FAs), particularly LA and alpha-LA (ALA), are crucial in fetal neurodevelopment and cell membrane formation. However, the journal article emphasizes the competition between LA and ALA for enzymatic conversion, which is critical in maintaining a balance of essential fatty acids (EFAs) necessary for fetal development.

LA is a precursor of arachidonic acid (AA), while ALA is a precursor of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are essential for fetal brain and retinal development. Excess LA relative to ALA disrupts the balance of essential FAs (EFAs) in the fetal brain by competing for the same enzymes, impairing neurological and cognitive development.

The present study reviewed the impact of ALA and LA on fetal growth and health.

Linoleic acid (LA) and alpha-LA (ALA)

LA and ALA are polyunsaturated FAs that can be desaturated and elongated into longer-chain FAs through enzymatic action. The paper elaborates that higher intake of dietary LA may lead to an overproduction of AA, which, in turn, triggers the production of inflammatory compounds, such as thromboxane, leukotriene B4, and prostaglandin E2. ALA and LA compete for enzymes involved in FA chain elongation and desaturation, reducing the production of DHA and EPA.

LA levels in the diet have substantially increased in Westernized regions. Since ALA and LA are metabolized by the same enzymes, increased intake of LA reduces ALA conversion to DHA and EPA. The optimal dietary LA-to-ALA ratio of 1:1 or 2:1 has increased manifold, now ranging between 4:1 and 20:1. This interference in the production of DHA and EPA is significant because DHA and EPA are critical for cardiovascular health and reducing inflammation. Therefore, this interference in the production of DHA and EPA may contribute to the health implications of excess LA intake.

Effects of linoleic acid (LA)

The paper discusses that while animal studies consistently show a correlation between high LA intake and increased inflammation, human studies are more varied, with some showing no significant relationship. The metabolism of LA leads to the synthesis of AA and pro-inflammatory eicosanoids (thromboxane prostaglandins and leukotrienes). This increased production of pro-inflammatory compounds can elevate inflammatory biomarkers,  such as tumor necrosis factor-α, interleukin-6, and C-reactive protein, which are associated with elevated incidence of chronic diseases. By contrast, metabolites of ALA are anti-inflammatory.

Animal studies suggested that weight gain due to LA stems from AA synthesis. For instance, the weight of pups of rodent dams fed a 7% LA diet was considerably elevated compared to those fed a 3% ALA diet. Further, rats on a high LA diet and low ALA increased weight in successive generations. However, the paper notes that human studies have shown mixed results, with some not observing the same degree of weight gain as seen in animal models. Besides, a strong association between leptin and LA has been reported.

The adipokine leptin can influence fetal development and regulate maternal metabolic conditions. The authors highlight that while LA alone has no effect on basal leptin synthesis, it significantly reduced leptin secretion in rat adipocytes in the presence of insulin.

Higher maternal intake of LA reduced plasma levels of leptin in rodents. In addition, altering dietary intake of LA between 1% and 8% of total energy showed varying effects on adiponectin and leptin in pregnant mice, suggesting a complex interaction that needs further exploration, particularly in human studies.

Linoleic acid (LA) and birth weight and length

LA intake and birth weight exhibit an inverted U-shaped correlation in humans. For instance, a low birth weight was observed at higher (> 8%) and lower (< 4%) maternal intake of LA in South Indians. The paper provides additional context, noting that this relationship may vary significantly based on ethnicity and environmental factors. Moreover, increased LA intake negatively affected erythrocyte ALA levels in mothers with low-birth-weight neonates.

An increased LA-to-ALA ratio in pregnancy resulted in lower placental blood flow but higher blood viscosity, leading to insufficient fetal growth. The authors suggest that this imbalance may also affect bone mineralization, contributing to shorter infant femur lengths.

Further, increased LA intake in pregnancy has been associated with shorter infant femur lengths. One study found that higher dietary intake of ALA and LA in the third trimester of pregnancy increased birth length.

Endocannabinoids and linoleic acid (LA)

Endocannabinoids (ECs) are mediators of placentation and are crucial in hormone development and regulation. ECs are generated from LA metabolism and act via the cannabinoid receptors 1 (CNR1) and CNR2.

These receptors play a significant role in body weight regulation, cardiac functions, and lipid and glucose metabolism, making their alteration by high LA intake a matter of concern, particularly during fetal development. They are associated with inflammation, obesity, cardiac functions, and lipid and glucose metabolism. Elevating dietary LA has been found to increase obesity in pregnant mice.

Further, a maternal diet with LAs constituting 6.21% of total energy has been reported to modulate CNR2 in fetal and maternal cardiac tissues in Wistar Kyoto rats.

Maternal dietary linoleic acid (LA) in pregnancy and obesity

A high LA intake during pregnancy influences childhood obesity risk and increases the risk of numerous chronic diseases, including hypertension, dyslipidemia, hyperinsulinemia, and endothelial dysfunction.

The paper emphasizes that this risk is particularly pronounced in animal studies, where a high LA-to-ALA ratio led to significant weight gain in offspring, but human data is more varied and requires further investigation. One study reported that pregnant mice fed a diet with a high LA-to-ALA ratio had male offspring with increased body weight.

Increased dietary LA in pregnancy correlated with a higher obesity risk in children at age 7. Besides, positive associations have been observed between increased LA-to-ALA ratio in cord blood and childhood obesity at age 10.

Concluding remarks

Together, studies in animals and humans have demonstrated that higher maternal LA intake in pregnancy potentially influences fetal growth and may predispose offspring to metabolic disorders. However, the paper stresses the need for further human studies to clarify these effects, given the mixed results observed in different populations.

Besides, excess LA in the diet during pregnancy may increase inflammatory markers in maternal blood and promote AA production and FA transfer across the placenta.

Further research is necessary to uncover the mechanisms underlying the observed effects.