Author- Marina McDonald, MS, PhD. March 31, 2020, Allergy Research Group
Are you familiar with DHA, also known as docosahexaenoic acid (pronounced doh-koh-sah-hex-ah-een-oh-ick acid)? DHA is the longest-chain omega-3 fatty acid, found in fish oil and in the diet in general.
Along with its omega-3 companion, eicosapentaenoic acid (EPA), DHA is essential for health at all ages, which is why they are also commonly referred to as essential fatty acids.[1],[2] Studies have shown that higher intakes of DHA and EPA are associated with a reduced risk of chronic diseases, including Alzheimer’s disease, age-related eye diseases, heart disease, stroke, joint pain, chronic fatigue, and total mortality.[3],[4],[5],[6],[7],[8]
Most organs in the body contain both EPA and DHA, but the brain and retina (the layer of tissue at the back of the eyeball) are unique in having very high levels of DHA and virtually no EPA.[9] In fact, DHA comprises nearly half of the polyunsaturated fatty acids (PUFAs) in the brain.[9],[10] It’s not surprising that a continuous supply of DHA is needed to keep our brains working throughout the lifespan.[11],[12],[13],[14]
Only small amounts of DHA can be made in the body from precursors such as ALA (alpha-linolenic acid, found in plant oils),[15] and it’s difficult to consume adequate amounts of DHA from the diet because it is found in so few food sources. The main way to obtain DHA is to consume seafood and/or omega-3 supplements, particularly formulations that are enriched in DHA. Let’s look at why DHA is so important, with a focus on the brain and eyes.
DHA and Alzheimer’s disease
Low levels of DHA are associated with cognitive decline, even in young adults. In a study of young women with an average age of 27 years, cognitive function (specifically attention) was poorer in those with lower DHA blood levels.[16] This reduced but normal level of cognition potentially provides a lower baseline from which cognition would continue to decline with age.
Individuals with Alzheimer’s disease (AD) have significantly less DHA in their blood and brain than those without AD.[17],[18] They also have lower levels of neuroprotectin D1 (NPD1),[19] a bioactive substance derived from DHA that keeps brain cells happy and healthy.[20],[21],[22]
Individuals who consume diets containing high levels of omega-3 fatty acids have a reduced risk of AD and other neurodegenerative conditions.[2] AD is characterized by an accumulation of beta-amyloid, a peptide that triggers the disease process.[23],[24] Studies suggest that both DHA and NPD1 inhibit beta-amyloid accumulation via multiple mechanisms.[22],[25],[26],[27]
The accumulation of beta-amyloid can begin decades before the clinical symptoms of AD become apparent,[28] so it is important to consume enough omega-3s throughout life.[16],[29],[30],[31] In one remarkable study, healthy postmenopausal women were first assessed for omega-3 levels in the blood, and then they were followed up with a brain MRI eight years later.[32] The researchers found that higher initial blood levels of DHA and EPA were associated with larger brain volumes after eight years, suggesting that DHA and EPA may protect against brain atrophy. The changes were especially pronounced in the hippocampus, a region associated with long-term memory.
In a placebo-controlled clinical trial, which directly tested the effects of DHA supplementation in adults age 55 and older with age-related cognitive decline, supplementation with 900 mg of DHA per day for six months doubled the plasma DHA levels and significantly improved memory and learning scores.[33]
Because brain lipids turn over slowly, it can take months of DHA supplementation to increase the brain levels of DHA.[34] In a study of patients with AD, supplementation with 2.3 grams of DHA daily produced a small but significant increase in the DHA levels in cerebrospinal fluid after six months.[35] However, it’s difficult to alter the course of AD once neurodegeneration has occurred.
Individuals with a genetic predisposition to AD may have difficulty transporting DHA into the brain, and are thus more resistant to DHA supplementation at any age.[36] The main culprit is a cholesterol carrier gene known as APOE4 (apolipoprotein E4), which is present in approximately 25% of the population.[37],[38],[39] Testing for APOE4 is not routine, so most of us do not know if we are carrying this gene (unless there is a family history of AD, which can be a clue).[40] DHA supplementation may help slow the progression of AD in APOE4 carriers, but only if supplementation begins at a very early stage.[30],[41]
Because inadequate levels of DHA and/or vitamins B and/or D are associated with cognitive decline,[42],[43] it makes sense that supplementation with multiple nutrients may be more effective than DHA alone.[44],[45] This concept was validated in a clinical trial in individuals with mild cognitive impairment, who had insufficient B vitamins as indicated by elevated blood homocysteine levels.[46] B vitamin supplementation helped slow the rate of cognitive decline, but only when DHA levels were in the upper normal range. DHA may also synergize with nutritional antioxidants such as astaxanthin. In an animal model of AD, the combination of DHA and astaxanthin helped slow the disease progression to a greater extent than astaxanthin alone.[47]
DHA and attention deficit hyperactivity disorder
Just as it sounds, the condition known as attention deficit hyperactivity disorder (ADHD) is characterized by difficulty concentrating, hyperactivity, and impulsive behavior. It affects 2 to 5% of the general population and is more prevalent in boys than girls.[48],[49] Although ADHD generally starts in childhood, it often continues into adulthood.
Children with ADHD were found to consume significantly less EPA and DHA on average,[50] and to have lower blood levels compared to their peers without ADHD.[49],[51],[52],[53] Moreover, children with lower blood EPA and DHA levels had more severe behavioral symptoms than those with higher levels.[54],[55],[56]
An intriguing study suggests that an insufficient supply of omega-3s during adolescence may hinder the development of impulse control, an aspect of ADHD.[57] Impulse control is required to control risky behaviors, and it develops during adolescence as the prefrontal cortex (PFC) of the brain matures. In 87 adolescent boys and girls enrolled in a brain imaging study, omega-3 intake was correlated not only with ADHD behavior, but also with localized PFC brain activity during a standardized test of impulse control.[57]
Clinical trials suggest that DHA supplementation can be beneficial for individuals with ADHD.[13],[58],[59],[60] In one placebo-controlled trial, 66 children with ADHD (between 6 and 18 years of age) were supplemented with 1,000 mg of DHA per day.[61] Improvements in behavioral measures were seen in the supplemented group compared to the placebo group after three months. This study provides further evidence of the benefits of DHA for the management of ADHD.
DHA and eye health
DHA is the most abundant polyunsaturated fatty acid (PUFA) in the retina, representing more than half of the total fatty acids.[62] Similar to the brain, the DHA-derived neuroprotective substance known as NPD1 helps support retinal health.[63],[64],[65],[66]
Several studies show that low blood DHA levels may increase the risk of age-related macular degeneration and that DHA may reduce this risk, as long as supplementation begins at an early stage of the disease.[67],[68],[69] In addition, DHA supplementation may improve dry eye disease,[70] diabetic retinopathy,[71] and some forms of glaucoma.[72]
Published case studies also suggest that dietary supplementation with DHA may improve reading ability in children with dyslexia.[73],[74] One theory is that the difficulty in reading experienced by children with dyslexia may be caused by abnormal development of their visual magnocellular (M) nerve cells, which mediate the ability to rapidly identify letters and their order.[75] M cell membranes require DHA to maintain their rapid responses, which would explain why DHA may be beneficial.[75]
As a nutraceutical for the eyes, DHA may be used alongside antioxidant or multivitamin formulations that provide lutein and zeaxanthin.[76],[77] Supplementation with highly concentrated DHA plus a multivitamin/mineral supplement containing lutein and zeaxanthin was associated with a progressive and significant improvement of macular function in individuals with diabetic retinopathy.[71] The DHA dosage was 1050 mg daily for 90 days.
How much DHA do we need?
The American Heart Association recommends consuming 3.5 ounces of fish at least twice per week, which would provide an average of about 500 mg of combined EPA and DHA per day.[78] (For children, the recommendation is for one to two servings of fish per week.)[79] Fewer than one in ten individuals in the population actually achieve this recommended level of fish intake.[80] Unless we take omega-3 supplements, many of us may thus have inadequate intakes.
Concerns related to the contamination of fish with heavy metals and organic pollutants also means that, despite the benefits of omega-3s in fish, we may not want to consume excessive quantities of wild fish.[81] Of further concern, a recent publication reports that the EPA and DHA content of farmed salmon has halved due to altered fish production and feeding methods,[82] meaning that average intakes of these nutrients are probably lower than ever before.[83]
Many standard fish oil supplements have more EPA than DHA, but newer supplements containing highly concentrated DHA are available. Such DHA-enriched supplements are often made with a process known as molecular distillation, which allows the preparation of highly concentrated and purified DHA.[1],[84]
Regarding dosage, studies correlating DHA levels in blood lipids with health statistics suggest that more than 1 gram of DHA daily, from food and/or supplements, may be required.[11],[35],[85],[86] The intake of up to 3 grams of omega-3s per day is generally recognized as safe.[13]
In short, to take care of your brain and eyes throughout life, reach for some pure DHA !
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