DHA Clinical Evidence

Weiser MJ, Butt CM, Mojaheri MH. Docosahexaenoic Acid and Cognition throughout the Lifespan. 2016 Feb; 8(2):99.

Topic:

What is the role of DHA in optimal cognition during development, adulthood, and aging?

Background:

DHA is the main omega-3 polyunsaturated acid found in the brain and affects neurological function in a variety of ways. What does human evidence say about DHA’s effects on cognition throughout the lifetime and how does it work?

Study Type:

Review paper

Summary:

The researchers outlined several findings from past research:

• • • There is substantial evidence regarding the importance of DHA during pregnancy and infancy on brain development, which affects the cognitive function of the child.
    • How much DHA is incorporated into neural tissues depends on the availability of DHA from the mother, which highlights the need for maternal consumption of dietary or supplemental sources of DHA to support optimal cognitive development.
    • It has been recommended that pregnant and nursing women consume at least 200 mg of DHA daily.
    • DHA supplementation may also extend the length of gestation.
    • Epidemiological studies and intervention trials probably underestimate the impact of DHA on cognition across the lifetime.

Conclusions:

“Overall, DHA appears to have the ability to influence many different signaling pathways, receptor systems, enzyme activities, membrane structures and dynamics that ultimately lead to overall better development, maintenance and aging of the CNS, resulting in optimal cognition throughout the lifespan. These benefits likely require a sustained supply of DHA across development, adolescence and adulthood to build and maintain sufficient pools and/or to replenish depleted neural stores. For those unable to obtain sufficient amounts of DHA via dietary means, supplemental DHA from fish oil or vegetarian (algal oil) sources is ideal. DHA-containing supplements are taken daily by millions of people worldwide and have been shown to be safe and well tolerated even at high doses.”

Harris WS, Kris-Etherton PM, Harris KA. Intakes of long-chain omega-3 fatty acid associated with reduced risk of death from coronary heart disease in healthy adults. 2008 Dec;10(6):503-9.

Topic:

In order to help prevent deaths from coronary heart disease (CHD) in the United States, what should an official target intake for EPA/DHA be?

Background:

Many organizations and agencies recommend consuming the omega-3 fatty acids EPA and DHA for overall cardiovascular health. How much is enough to help prevent death from CHD?

Study Type:

Meta-analysis

Results:

Of the six epidemiological studies analyzing the relationship between EPA and DHA intake and risk of death from CHD, five have reported statistically significant inverse trends. In other words, people consuming higher levels of these omega-3 fatty acids tend to have lower death rates from CHD. At an average EPA + DHA intake of 566 mg per day, the relative risk reduction is 37 percent.

Conclusions:

“Coincidentally, two servings per week of oily fish (the current American Heart Association recommendation) would provide 400 to 500 mg/d. We conclude, therefore, that an intake of 400 to 500 mg/d of EPA + DHA is achievable by diet alone and would be expected to significantly reduce risk for death from CHD in healthy adults.”

Lavie CJ, et al. Omega-3 polyunsaturated fatty acids and cardiovascular diseases. 2009 Aug 11;54(7):585-94.

Topic:

What is the target dosage for EPA/DHA for the prevention of cardiovascular disease?

Background:

Evidence from large randomized controlled studies, as well as retrospective epidemiological studies, indicates that omega-3 fatty acid therapy is beneficial in primary and secondary prevention of cardiovascular disease (CVD). How much should individuals consume daily?

Study Type:

Review

Results:

The researchers outlined several findings from past research:

• • • 4 controlled studies of nearly 40,000 participants who were randomly selected to supplement with either EPA alone or EPA plus DHA have shown that omega-3 therapy is helpful for primary prevention of CVD, recovery from heart attack, and with heart failure.
    • Retrospective epidemiological studies also show benefits of EPA and DHA in primary and secondary prevention of CVD.
    • The target EPA + DHA consumption should be at least 500 mg/day for healthy individuals and 800-1,000 mg/day for people with known coronary heart disease and heart failure.
    • Further studies are needed to determine the best dose and ratio of DHA and EPA for providing cardiovascular protection to people at risk of CVD as well as for the treatment of people with CVD.

Conclusions:

“Convincing evidence from extensive research over the past 3 decades points out the potential beneficial effects of ω-3 PUFA in primary prevention, CHD and post-MI, SCD, HF, atherosclerosis, and AF. Based on the growing evidence for the benefits of fish oils, we agree that this story represents a “fish tale with growing credibility.” We also agree with Rogans’ comment from over 20 years ago that “fish oil is a whale of a story, that not surprisingly gets bigger with every telling”

Bakerac SJ, Al-Najadah R. Effect of ingesting fish oil on serum lipid and lipoprotein concentration in exercising and nonexercising women. 1996;6(4):287-297.

Topic:

How do fish oil, fish oil plus exercise, or exercise only affect blood lipids in pre and postmenopausal women?

Background:

Elevated blood lipids are considered a risk factor for cardiovascular disease. Does fish oil have an effect on blood lipid levels?

Study Type:

Human clinical intervention trial

Study Design:

Randomized, controlled: Women were randomly divided into three groups: fish oil, fish oil plus exercise, or exercise only for 12 weeks. A control group followed their normal routine for the duration of the study period. Blood lipids were measured at baseline and at four intervals of 1 week in all subjects. Body fatness was also measured.

Dosage:

1 fish oil capsule daily, containing 171 mg EPA and 114 mg DHA

Subjects:

30 premenopausal and 30 postmenopausal women in the treatment groups, plus 10 women in the control group

Results:

Both the fish oil and fish oil plus exercise groups experienced a decrease in LDL cholesterol. There were no changes in HDL cholesterol or triglycerides in any group. Both groups that exercised experienced decreases in body fat.

Véricel E, et al. Moderate oral supplementation with docosahexaenoic acid improves platelet function and oxidative stress in type 2 diabetic patients. 2015 Aug;114(2):289-96.

Topic:

Can DHA supplementation correct platelet dysfunction and reduce oxidative stress in patients with type 2 diabetes?

Background:

Diabetics’ blood platelets — cell fragments responsible for blood clotting — are characterized by hyperactivation and high levels of oxidative stress. These alterations paves the way for the development of blood clots that can cause heart attack and stroke.

Study Type:

Human clinical intervention trial

Study Design:

Randomized, double-blind, placebo-controlled two-period crossover pilot study. Participants took either DHA or placebo for two weeks. After a six-week washout period, they then switched interventions. Because the study was double-blinded, neither the women nor the researchers knew which two-week period was the treatment period and which was the placebo period.

Dosage:

400 mg/day for 2 week periodsSubjects:11 post-menopausal women with type 2 diabetes

Results:

DHA resulted in a 46.5% reduction in platelet aggregation (clumping) and a decrease in metabolites of activated platelets as well as markers of oxidative stress. Placebo, on the other hand, had no effect on any parameters tested.

Conclusions:

“Our findings support a significant beneficial effect of low intake of DHA on platelet function and a favourable role in reducing oxidative stress associated with diabetes.”

Wang Q, et al. Effect of omega-3 fatty acids supplementation on endothelial function: a meta-analysis of randomized controlled trials. 2012 Apr;221(2):536-43.

Topic:

What effect does omega-3 fatty acid supplementation have on endothelial function?

Background:

Previous studies have reported an inverse association between omega-3 fatty acid supplementation and the risk of cardiovascular disease. This may be due to omega-3s’ effect on endothelial function. (Endothelial cells control blood pressure, vascular permeability, blood coagulation, arterial stiffness, and inflammation.)

Study Type:

Meta-analysis

Study Design:

Researchers identified randomized, placebo-controlled studies from several scientific databases and pooled their effects. Sixteen eligible studies, involving 901 participants, were included in the meta-analysis. They used two measures to assess whether omega-3s impacted endothelial function: flow-mediated dilation (FMD) and endothelium-independent vasodilation (EIV).

Dosage:

Varied by study

Results:

Omega-3 supplementation significantly increased FMD by 2.3% compared with placebo at a dose of 0.45 to 4.5 grams per day over a median of 56 days. There was no significant change in EIV after omega-3 supplementation.

Conclusions:

“Supplementation of omega-3 fatty acids significantly improves the endothelial function without affecting endothelium-independent dilation.”

Yamagat K. Docosahexaenoic acid regulates vascular endothelial cell function and prevents cardiovascular disease. 2017 Jun;16(1):118.

Topic:

What is the effect of DHA on vascular endothelial cells and what does the research say about its potential to prevent circulatory diseases?

Background:

Epidemiological studies have shown an association between high dietary consumption of oily fish and reduced rates of heart attack. What is the mechanism of action behind DHA for preventing cardiovascular disease?

Study Type:

Review

Results:

The researchers outlined several findings from past research regarding how DHA affects vascular endothelia cells:

• • • DHA has a protective effect on vascular endothelial dysfunction in vitro
    • DHA lowers plasma triglycerides and inflammation, and has been shown to suppress platelet aggregation.
    • Fish consumption has been shown to prevent coronary heart disease, stroke, and total mortality after stroke in humans.

Conclusions:

“Many studies have shown that DHA has an important role in the function of vascular endothelial cells. During regular consumption of n-3 PUFAs, DHA has the potential to decrease endothelial dysfunction and prevent CVD through effects on endothelial metabolism, inflammation, thrombosis, and arrhythmia. Thus, dietary DHA prevents endothelial dysfunction and regulates vascular health. Intake of foods rich in DHA such as fish has the potential to make a significant contribution to the prevention of CVD.”

Ebrahimi M, et al. Omega-3 fatty acid supplements improve the cardiovascular risk profile of subjects with metabolic syndrome, including markers of inflammation and auto-immunity. 2009 Jun;64(3):321-7.

Topic:

Do purified omega-3 fatty acid supplements improve the cardiovascular risk profile of subjects with metabolic syndrome?

Background:

Fish oil is rich in anti-inflammatory omega-3 fatty acids. Do omega-3 supplements positively impact various measures of health in people with metabolic syndrome?

Study Type:

Human clinical intervention trial

Study Design:

Randomized, controlled. Participants were randomly divided into two groups. Half were given one fish oil capsule daily for six months, while the other half did not receive any supplementation.

Dosage: 1 gram of fish oil per day (providing 180 mg EPA and 120 mg DHA)

Subjects:

89 participants with metabolic syndrome (47 in the fish oil group and 42 in the placebo group), average age 53 (SD +/- 12 years)

Results:

Omega-3 supplements caused a significant fall in body weight, systolic blood pressure, LDL cholesterol, total cholesterol, triglycerides, high-sensitivity C-reactive protein, and Hsp27 antibody titers. No significant changes occurred among controls.

Conclusions:

“It appears that omega 3 improves the cardiovascular risk profile of subjects with metabolic syndrome, having effects on weight, systolic blood pressure, lipid profile and markers of inflammation and autoimmunity.”

Neubronner J, et al. Enhanced increase of omega-3 index in response to long-term n-3 fatty acid supplementation from triacylglycerides versus ethyl esters. 2011 Feb;65(2):247-54.

Topic:

Is there any difference in absorption between EPA and DHA in triglyceride form versus ethyl ester form?

Background:

Whether or not the body absorbs different forms of EPA and DHA identically is the subject of much debate. This study determined to find out if there is a difference in absorption between the re-esterified triglyceride form versus the ethyl ester form.

Study Type:

Human clinical intervention trial

Study Design:

Randomized, double-blinded, placebo-controlled. Participants were randomly assigned to one of three groups: 1. Fish oil concentrate (re-esterified triglyceride form), 2. Placebo (corn oil), or 3. Fish oil concentrate (ethyl ester form). They took their assigned gelatin-coated soft gels (4 per day) for 6 months. Their omega-3 levels were ascertained at the beginning of the study, after 3 months, and at the end of the study using the omega-3 index.

Dosage:

1 gram + 0.67 gram per day

Subjects:

150 volunteers

Results:

Both groups treated with omega-3 supplements experienced significant increases in the omega-3 index from baseline to 3 months and 6 months. However, it increased 15% greater in the triglyceride group than the ethyl ester group.

Conclusions:

“A six-month supplementation of identical doses of EPA+DHA led to a faster and higher increase in the omega-3 index when consumed as triacylglycerides than when consumed as ethyl esters”

Burri L, et al. Marine omega-3 phospholipids: metabolism and biological activities. 2012 Nov 21;13(11):15401-19.

Topic:

What is the metabolic bioavailability of EPA and DHA in phospholipid form versus triglyceride form?

Background:

Previous research has shown that EPA and DHA are better absorbed in the triglyceride form than the ethyl ester form. New innovative marine raw materials, such as krill oil and herring roe, provide EPA and DHA in a phospholipid (PL) form. Is the PL form even more bioavailable than the triglyceride form?

Study Type:

Review

Results:

The researchers outlined several findings from past research on the biological activities and differences in bioavailability of omega-3s in the PL form versus the TG form:

• • • The PL form was better at improving the metabolic profile of obese mice than the TG form.
    • The PL form was more efficiently taken up by tissues such as liver, fat and muscle tissue when given in the PL form.
    • Some evidence in rats indicates the PL is a more efficient delivery form of omega-3s to the brain than the TG form. In fact, the incorporation of DHA was more than twice as high from the PL form as the TG form in the brain, liver and kidneys. Additionally, higher DHA incorporation was also seen in the adrenal gland, brown fat, thymus and ulveal tract/retina. DHA uptake was significantly higher in 11 out 14 brain regions after administration of the PL form versus the TG form.

Conclusions:

“Traditional PLs used within nutrition or for pharmaceutical and cosmetic applications do not normally contain n-3 PUFAs, or at best only very small amounts. The increased accessibility of marine PLs during recent years opens up new possibilities for the use of PLs not only as a superior nutritional source of n-3 PUFAs, but also for use in the pharmaceutical, cosmetic and functional food industries.”

DHA is an omega-3 fatty acid that is as important to human physiology as vitamins and minerals. In theory, this long-chain polyunsaturated fatty acid can be manufactured in the body from ALA, which is abundant in most diets; however in reality, the conversion process is very inefficient. Therefore, it is recommended that preformed DHA be consumed through the diet or supplements. DHA affects the physiology and function of cells and tissues through a variety of ways. It influences the structure and function of cell membranes, is involved in cell signaling and communication, affects how genes are expressed, and plays a role in the production of lipid mediators.