Essential Fatty Acid Levels Low in Fragile X Patients, Study Finds

Supplementing fatty acids may improve brain health, researchers say

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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People with fragile X syndrome have significantly lower levels of fatty acids — a type of fatty molecule essential for brain health — in the blood than do healthy people, a study showed.

These findings add to data from previous studies reporting lower-than-normal cholesterol levels in this patient population. Overall, according to the investigators, the research highlights an association between fragile X and a general deficiency in fatty molecules.

“Our results provide new directions for preclinical research to explore the underlying causes and effects of low [blood fatty molecules] in [fragile X] and further explore treatment strategies,” the team wrote.

Some of these strategies could involve supplementation with fatty acids. Such approaches have shown promise in mouse models of the disease, and in trials of people with attention deficit hyperactivity disorder (ADHD) — a psychiatric disorder that also affects fragile X patients.

The study, “Alteration of Fatty Acid Profile in Fragile X Syndrome,” was published in the International Journal of Molecular Sciences.

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Fragile X is caused by a deficiency in the fragile X mental retardation protein (FMRP) that’s critical for proper brain function. The most well-recognized fragile X symptoms include intellectual disabilities and behavioral problems, such as autism spectrum disorders (ASDs) and ADHD.

Previous research showed that an absence of the FMRP protein is also associated with a number of metabolic changes. These include decreased fat storage and low levels of cholesterol in the blood and in specific cellular structures involved in nerve cell function.

Essential fatty acids in fragile X

Changes in the profile of fatty acids — the most abundant fatty molecules in the brain along with cholesterol — have been reported in a number of neuropsychiatric disorders, including intellectual disability, ADHD, and ASDs.

These molecules play an important role in brain development, blood flow, inflammation, and production of brain-protective molecules.

However, the fatty acid profile of fragile X patients has not yet been investigated.

Now, researchers in Canada, Argentina, and Chile compared the blood fatty acid profile between fragile X patients and healthy people.

Two sets of patients were evaluated: one including 23 Argentinian patients, and the other involving 11 French-Canadians. Altogether, data from 34 children, adolescents, and adults with fragile X — 28 males and six females, with a mean age of 22.8 years — were analyzed. The team also factored in data from 34 age- and sex-matched healthy people.

Blood samples were collected and analyzed for fatty acids belonging to three families: saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs).

PUFAs include omega-3 and omega-6 fatty acids, which are two types of essential fatty acids that must be obtained from dietary sources. Both are critical for the body to function.

Fragile X patients showed lower levels for all essential fatty acids relative to matched healthy people. These differences reached statistical significance for the majority of measured SFAs, PUFAs, and MUFAs.

The largest difference involved total PUFAs, with fragile X patients having 22% lower omega-6 levels and 16% lower omega-3 levels than healthy controls.

The levels of all omega-6 PUFAs, and two of the four omega-3 PUFAs measured, were significantly lower in patients relative to the control group.

Comparable results were obtained when analyses were limited to males in both groups.

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A significant decrease in the ratio between certain omega-3 fatty acids also was observed in fragile X patients, which suggests alterations in the activity of enzymes involved in fatty acid metabolism, according to researchers.

These findings highlight that fragile X patients “present an abnormal profile of FAs, specifically FAs belonging to the [omega-3] family, that might open new avenues of treatment to improve core symptoms of the disorder,” the team wrote.

New therapeutic targets

Notably, subgroup analyses showed that differences in essential fatty acid levels were only observed among adults, but not in children or adolescents. The team noted, however, that this may be due to the relatively low number of participants in these age groups — nine children and four adolescents.

“Further studies including young children are warranted to characterize the FA [fatty acid] profile abnormalities and, thus, to determine if there is an age range for early intervention in terms of FA supplementation that could benefit this population,” the researchers wrote.

The essential fatty acid profile observed in fragile X patients shared many similarities with those reported for people with ASDs and ADHD, both of which are commonly observed in fragile X patients.

Previous studies have suggested that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), two types of omega-3 PUFAs present in fish oil, might be of therapeutic benefit for ASD and ADHD, and could therefore also benefit fragile X patients.

In line with that hypothesis, DHA administration was found to restore nerve cell function and improved social behavior in a mouse model of fragile X.

Among the limitations of this new study, according to the team, was the lack of monitoring of a number of factors that could influence fatty acids profiles. Those include sex, diet, and measures of body fat. Potential associations between essential fatty acid levels and clinical features also were not analyzed, due to “inconsistent and insufficient data,” the team wrote.

“The identification of clinical traits related to specific PUFAs will help identify potential outcomes for future trials with FA supplementation,” the researchers wrote.

The team noted the difficulties of recruiting and reaching a sufficiently large sample size, given that fragile X is a rare disease.

“Multi-centric studies can help to perform larger scale population studies to validate our results,” they concluded.