From ... in Biology — Nov 27, 2024

High Linoleic Acid Intake During Pregnancy May Harm Fetal Growth and Raise Obesity Risk

If you're pregnant or planning to become pregnant, you might want to take a closer look at your diet, particularly your intake of linoleic acid (LA).

Consuming too much of this omega-6 fatty acid during pregnancy could have negative effects on your baby's growth and long-term health, according to research published in Nutrients.

LA is found in seed oils, processed foods and even some seemingly healthy options like chicken, nuts and seeds. While it's believed to be an essential fatty acid that your body needs, the modern Western diet typically provides far more than necessary. It is virtually impossible to not receive the necessary amount of 500 mg in any diet that includes food, making it questionable at best if it is indeed an essential fat. Over the past few decades, LA consumption has skyrocketed from about 2% of daily energy intake, or about 2 to 4 grams a day, to 7%, or 19 grams daily. This dramatic increase is causing unintended consequences for pregnant women and their developing babies. Remember you likely only need 500 mg (one half of one gram) to meet your requirements.

Your body uses linoleic acid and its omega-3 counterpart, alpha-linolenic acid (ALA), to produce longer-chain fatty acids crucial for fetal development. These include arachidonic acid (AA) from LA, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from ALA. These fatty acids play vital roles in brain and retinal development, cell membrane formation and overall growth. However, LA and ALA compete for the same enzymes in this conversion process. When you consume too much LA, it interferes with the production of beneficial EPA and DHA from ALA. The optimal ratio of LA to ALA in your diet should be around 1:1 or 2:1. Unfortunately, the current excess of LA in many diets has pushed this ratio to as high as 20:1, disrupting the delicate balance needed for optimal fetal development.

High levels of LA in your diet during pregnancy may trigger increased infiammation, negatively impacting fetal growth. When your body metabolizes LA, it produces AA and other proinfiammatory compounds like prostaglandins, leukotrienes and thromboxane.

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These substances increase levels of infiammatory markers such as interleukin-6, tumor necrosis factor-alpha and C-reactive proteins. Chronic infiammation during pregnancy has been linked to various adverse outcomes, including premature labor, intrauterine growth restriction and low birth weight. Animal studies have shown that a high-LA diet increases the production of these infiammatory compounds in pregnant mothers. These findings suggest that excessive LA intake creates an infiammatory environment that's harmful for your developing baby. LA intake during pregnancy may also have a significant infiuence on the baby's birth weight and length — two important indicators of long-term health. Interestingly, the relationship between LA and birth weight isn't straightforward. Some studies have found an inverted U-shaped correlation, where both low (<4% of energy) and high (>8% of energy) LA intakes were associated with lower birth weights. Other research has shown that high maternal LA intake in early pregnancy is linked to decreased birth weight and higher rates of small-for-gestational-age babies.

The effects of high maternal LA intake don't stop at birth — they may extend well into the child's future. Studies have shown that children born to mothers who consumed high levels of LA during pregnancy have an increased risk of obesity by age 7. This heightened risk of childhood obesity is concerning because it sets the stage for various chronic diseases later in life, including high blood pressure, dyslipidemia, chronic infiammation, hyperinsulinemia and endothelial dysfunction. Animal studies support these findings, showing that offspring of mothers fed high-LA diets during pregnancy had higher body weights at weaning and increased fat deposition. The mechanisms behind these long-term effects are still being investigated, but they likely involve changes in gene expression, alterations in fat metabolism and disruptions

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to the endocannabinoid system, which plays a role in regulating appetite and metabolism.

A separate animal study also uncovered concerning effects of consuming too much LA during pregnancy and early life. Australian researchers found that high maternal LA intake altered the fatty acid composition and plasmalogen levels in offspring brains, with more pronounced changes in males. Plasmalogens are a class of lipids vital for brain cell protection and function. The researchers observed increased levels of infiammatory mediators like arachidonic acid in the brains of male offspring exposed to high-LA diets. Additionally, they found decreased ratios of DHA to n-6 docosapentaenoic acid (DPA) in both male and female offspring brains when fed high-LA diets after birth. DHA is crucial for optimal brain development, while elevated n-6 DPA has been linked to learning and memory deficits. These findings suggest that excessive LA consumption during pregnancy and early life negatively impacts neurodevelopment, particularly in male offspring. Intriguingly, the study revealed sex-specific effects of high-LA diets on offspring brain composition. Male offspring showed greater diversity in brain fatty acid concentrations compared to females when exposed to elevated LA levels. This suggests that the developing male brain may be more susceptible to the effects of high-LA intake.

Consumption of high-LA diets during pregnancy and early life also impact children's endocannabinoid system, which is crucial for early brain development. The study found

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that several endocannabinoids and related compounds, including anandamide (AEA), 2- arachidonoylglycerol (2-AG) and AA, were significantly elevated in offspring exposed to postnatal high-LA diets. Male offspring showed more pronounced changes in endocannabinoid levels compared to females, further emphasizing the sex-specific nature of LA's effects. Additionally, the research revealed that high-LA diets significantly increased testosterone levels in male offspring. These alterations in endocannabinoid signaling and hormone levels could have far-reaching consequences for brain function, behavior and overall health. The endocannabinoid system plays vital roles in neurotransmitter regulation, synaptic plasticity and various cognitive processes, making these findings particularly concerning for long-term brain health and development.

Diet during pregnancy doesn't just affect the baby's brain — it also impacts kidney development. Recent research on rats has shown that a maternal diet high in LA alters the expression of genes crucial for kidney formation in embryonic offspring. Specifically, the study found decreased expression of Ret and Gdnf, genes responsible for branching morphogenesis — a critical process in early kidney development. This reduction could lead to decreased nephron formation, which is essential for proper kidney function. The study also noted that these genetic alterations occurred despite no changes in kidney weight at the embryonic stage, highlighting the importance of looking beyond organ size when assessing developmental impacts. The findings raise concerns about the long-term consequences of excessive LA consumption during pregnancy, as reduced nephron endowment in humans has been linked to an increased risk of various diseases in adulthood. Further, high linoleic acid intake during pregnancy could disrupt important cellular signaling pathways in the baby's developing kidneys. The study revealed that offspring

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from mothers consuming a high-LA diet showed decreased expression of mTOR, Akt3 and Prkab2 — key components of the megalin signaling pathway. Megalin, an endocytic receptor, plays a vital role in the reabsorption of macromolecules filtered by the kidneys. The mTOR pathway, in particular, is crucial for cell metabolism, proliferation and growth. Its reduced expression could impact protein synthesis and mRNA translation in cell growth. Additionally, the downregulation of both mTOR and Prkab2 might affect autophagy processes, infiuencing cell viability and development. These alterations in cellular signaling could have far-reaching consequences for kidney function and overall health. Importantly, these changes were observed at the embryonic stage, which means the maternal diet's impact on fetal kidney development begins very early in pregnancy. The effects of excessive LA intake during pregnancy extend to other organ systems as well.

A mother's diet during pregnancy also has lasting impacts on her child's liver function. Research published in the International Journal of Molecular Sciences shows that consuming high levels of LA while pregnant may alter lipid metabolism in offspring, setting them up for liver issues later in life. In this study, researchers fed pregnant rats either a low-LA diet (1.44% of calories from LA) or a high-LA diet (6.21% of calories from LA) to mimic typical Western consumption levels. They then examined the effects on the adolescent offspring's liver health and function. The results revealed concerning changes in cholesterol storage, fatty acid handling and expression of key genes involved in lipid metabolism. In other words, a mother's high intake of vegetable oils and other LA-rich foods during pregnancy could negatively impact her child's liver development and function. Male and female offspring were affected differently by their mother's high-LA intake. In male offspring, maternal high LA decreased liver cholesterol levels and increased

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expression of PPAR γ , a gene involved in fatty acid storage. For female offspring, maternal high LA increased expression of genes involved in cholesterol synthesis. The changes observed could increase risk of nonalcoholic fatty liver disease (NAFLD) or other metabolic issues later in life, especially when combined with a poor diet in adulthood. While this study was in rats, it raises important questions about how maternal diet may be impacting human liver development and long-term health outcomes. An additional concerning finding was that the mother's high-LA intake increased blood levels of uric acid in male offspring. There was also an interaction effect on uric acid levels in females. While the levels were still within normal physiological range, elevated uric acid is associated with a range of health issues including kidney disease, metabolic syndrome and cardiovascular disease. Uric acid activates the immune system and alters kidney cell function, promoting infiammation and tissue damage. These findings add to the growing body of evidence that consuming high levels of seed oils rich in linoleic acid during pregnancy may have unintended negative consequences for offspring health across multiple organ systems.

Research continues to build showing that excessive LA intake during pregnancy puts your future children at risk. Scientists explained in Current Medicinal Chemistry that high intake of foods rich in omega-6 polyunsaturated fats (PUFAs), like LA, are "transformed into infiammatory metabolites promoting the pathogenesis of cardiovascular diseases, cancer, and autoimmune or infiammatory conditions." Further: "An elevated intake of n-6 PUFA, specifically LA, during pregnancy [negatively] infiuences children's motor, cognitive, and verbal development during infancy and early childhood. Similarly, they could harm the placenta and the

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development of other fetal organs such as the fat tissue, liver, and cardiovascular system …" A growing fetus requires lots of energy, so supporting cellular energy production is key to a healthy pregnancy and ensuring future generations are full of vitality. Optimizing your mitochondrial function is crucial for improving your cellular energy, but LA is a mitochondrial poison. To optimize your mitochondrial function, reduce consumption of LA as much as possible. I recommend keeping your intake below 5 grams a day. To achieve this, it's best to eliminate seed oils and even fruit-based oils like olive or avocado from your diet, as these are often mixed with less expensive seed oils. Instead, use ghee, butter or beef tallow for cooking. Stay away from ultraprocessed foods, which typically contain high amounts of seed oils. It's advisable to avoid dining out as well, since most restaurants use seed oils in their cooking, sauces and dressings. Additionally, limit your consumption of chicken and pork, which are typically high in LA. Focus on incorporating bison, lamb and other ruminant meats as your primary protein sources instead. By making these dietary adjustments, you help create an optimal nutritional environment for your developing baby, reducing the risk of adverse outcomes due to excessive LA intake and setting the stage for optimal long-term health.

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