2016 Omega-3 Science Update

Nutritional OutlookNutritional Outlook Vol. 19 No. 7
Volume 19
Issue 7

The latest crop of omega-3 research nets positive data for depression, eye health, children’s health, and more.

Photo © iStockphoto.com/Merrimon

Omega-3 fatty acids from fish and other sources are fats with a uniquely diverse range of health applications. Boosting intake of these healthy fats-particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)-through diet and supplementation can support the body in multiple ways.

For instance: aging results in lower neural concentrations of omega-3 fatty acids, leading to neuronal loss and a decline in cognitive function; however, recent studies show that omega-3 fats can enhance neuron signaling and synaptic plasticity, while preserving gray and white matter in the brain.1 Another example: inflammation is increasingly linked to chronic disease, but research shows that omega-3 fats play important roles in reducing inflammation by lowering the concentration of pro-inflammatory eicosanoids such as thromboxane B2 and leukotriene B4.2 And yet another example: studies show that omega-3 fatty acids may benefit arterial structure by reducing arterial stiffness and improving endothelial function, while simultaneously reducing oxidative stress and inflammation and favorably modifying the expression of enzymes involved in the process of atherosclerosis.3

The ability of omega-3 fatty acids to influence so many processes in the human body is what makes omega-3 research so exciting. Ahead, we highlight some of the most recently published human studies showing beneficial effects of supplementation with omega-3 fatty acids on several health conditions.


Reducing Heart Risk: Omega-3s Plus Vitamin B12

Given the role omega-3 fats play in heart health and vascular health, Tao Huang and colleagues from Zheijang University in China recently studied the effects of fish oil EPA and DHA on several risk factors of heart disease in healthy young adults.4 The researchers also had another objective: to evaluate possible synergistic effects of the omega-3 fatty acids and vitamin B12, a vitamin known to lower homocysteine levels (a risk factor for heart health).

In the eight-week randomized controlled trial, 30 subjects with a mean age of 23 were divided into three groups. One group supplemented with vitamin B12 (1,000 mcg/day). The second group supplemented with 2 g of fish oil daily (containing 490 mg DHA and 98 mg of EPA per gram). The third group was given a combination of both the fish oil and vitamin B12 supplements.

The researchers conducted blood tests to monitor the impact of supplementation on levels of plasma homocysteine, ferritin (a measure of iron status), triglycerides, uric acid, and C-reactive protein (a measure of inflammation). Measurements taken during the study at four and eight weeks showed that all groups experienced significant decreases in all measures. Plasma homocysteine concentration declined from baseline by 22% in the vitamin B12 group, by 19% in the fish oil group, and by 39% in the combination-supplement group. While each nutrient individually was able to significantly lower markers of heart risk, the fish oil and vitamin B12 combination had a substantial synergistic impact, indicating a powerful benefit for heart and vascular health.


Eye Health: Protecting Retinal Function

X-linked retinitis pigmentosa is a genetic condition affecting the retina of the eye that leads to progressive vision loss in boys and young men. In those with the condition, night blindness occurs initially with progressive constriction of the visual field, leading to blindness at an average age of 45. Where do omega-3 fatty acids come in? Science indicates that individuals with this condition have a reduced ability to synthesize the omega-3 fatty acid DHA from other fatty acids.5 For this reason, researchers believe that oral supplementation with DHA may help bypass this defect and potentially slow the progression of the disease.

In an earlier, 2014-published trial-the DHAX (DHA in X-linked Retinitis Pigmentosa) trial-researchers found no effect from DHA supplementation on slowing the loss of cone or rod function in males with retinitis pigmentosa6. Recently, however, those same researchers published a paper analyzing ancillary outcomes of the original trial. Specifically, they looked at the effects of DHA supplementation in those participants who completely adhered to the treatment protocol.7

This ancillary analysis included 49 males who were 7 to 31 years old. Of those subjects, 29 had received DHA (30 mg/kg body weight daily in the triglyceride form), while 22 received a placebo, for four years. Visual parameters were measured yearly, while DHA concentrations were assessed every six months.

The researchers found that red blood cell levels of DHA increased fourfold over placebo in those supplementing with DHA. While visual parameters like visual acuity, ability to discriminate shapes, or the appearance of the fundus of the eye were not significantly different between groups, the researchers did detect statistically significant benefits in favor of DHA supplementation for reducing the progression of dark adapted thresholds, a measure of night vision. Furthermore, DHA supplementation also helped to attenuate the decline in visual field sensitivity over the four-year period. This sensitivity was determined to be linked to red blood cell levels of DHA-that is, higher concentrations of DHA led to less of a decline.

These findings indicate that DHA supplementation can benefit certain parameters of retinal health and visual function in individuals with retinitis pigmentosa.

The researchers further advocated for additional studies using higher doses of DHA in order to try to induce greater benefits. Based on the DHA dose of 30 mg/kg body weight administered in the study, red blood cell DHA concentrations averaged 10.9%. By extrapolating the results comparing the mean red blood cell levels of DHA and loss of visual field sensitivity, the authors postulated that a red blood cell DHA concentration of 17% could fully attenuate the loss of visual field sensitivity. An estimated DHA dose to attain this level of red blood cell saturation would be 45 mg/kg body weight per day.7


Anti-Inflammatory Effects During Pregnancy

Obesity is a condition that can lead to the development of insulin resistance, with chronic metabolic inflammation a contributing factor. The onset of pregnancy in obese women often accelerates the development of insulin resistance, which can lead to complications for the developing fetus.8 Because omega-3 fatty acids have anti-inflammatory effects, theoretically they could help to lower inflammation in pregnant women who are obese.

Previous studies have shown benefits from increasing fish intake and omega-3 supplementation during pregnancy, including increasing gestation length and reducing the risk of pregnancy complications.9 A recently published study led by Maricela Haghiac from the Department of Reproductive Biology at MetroHealth Medical Center (Cleveland, OH) sought to evaluate the effects of omega-3 fatty acid supplementation in obese pregnant women on the inflammatory status of the placenta and adipose tissue.8

This randomized placebo-controlled trial enrolled pregnant women with a body mass index (BMI) greater than 25. The women were asked to consume a supplement containing DHA and EPA (2 g/day), or a placebo, from prior to 16 weeks of gestation until delivery. Blood measurements of cytokines and fasting glucose and insulin levels were conducted at enrollment and then again between weeks 34 and 36 of pregnancy. Placental samples and cord blood were obtained immediately after delivery. In the case of caesarean delivery, subcutaneous abdominal adipose tissue was taken. Samples were frozen in liquid nitrogen.

While omega-3 supplementation was not found to modify insulin resistance in this study, there was a significant decrease in C-reactive protein (a measure of inflammation) in the omega-3 supplement group versus the placebo group. The genetic expression of pro-inflammatory cytokines IL-6, IL-8, and TNF-α also significantly decreased in the adipose and placental tissue of those in the omega-3 group.

These findings suggest an overall reduced inflammatory response in the placenta and adipose tissue of obese pregnant women, supporting the benefits of omega-3 fats for this population.


Reduction of Brain Oxidative Stress in Depression

Psychiatric conditions, including depression, may share many of the same underlying imbalances that are associated with heart and vascular disease. These include increased inflammation, endothelial abnormalities, and increased plasma levels of homocysteine, a marker for heart and brain risk. For this reason, omega-3 supplements may be of benefit for psychiatric health. A recent meta-analysis including 19 randomized controlled trials found that supplementation with omega-3 fatty acids resulted in significant benefits in individuals diagnosed with major depression, as well as those with depressive symptoms but no diagnosis of major depression.10

Lately, researchers have been narrowing in on the impact of oxidative stress in brain tissue on the progression of major depression. Shantel Duffy and colleagues at the Brain & Mind Research Institute of the University of Sydney in Australia set out to study the benefits of omega-3 fatty acids for the reduction of oxidative stress in the brain of adults at risk of depression.11

Fifty-one adults were randomized to receive omega-3 fatty acid supplements (1200 mg DHA + 800 mg EPA daily) or a placebo for 12 weeks. Magnetic resonance imaging as well as neuropsychological and self-report assessments were performed at baseline and after 12 weeks. Depressive symptoms were tracked using a validated questionnaire. In addition, as an indicator of oxidative stress, glutathione levels were measured in the thalamus, a key area of the brain for processing sensory information. While glutathione is one of the most important antioxidants in the body, research has shown that increased thalamic glutathione levels are a marker for increased oxidative stress in brain tissue.

In the placebo group, glutathione concentration in the thalamus increased significantly by the end of the study, and the increase in thalamic glutathione concentration was associated with a rise in depressive symptoms. In the omega-3 supplement group, however, this increase was significantly attenuated.

This study demonstrates that omega-3 fatty acids may help improve symptoms of depression by effectively reducing the rise of oxidative stress levels in the brain.


Improvement of Liver Function in Children

The prevalence of childhood obesity grows hand in hand with associated health problems. A recent review of general population studies and studies in obese children suggests, for instance, that the occurrence of non-alcoholic fatty liver disease (NAFLD), a major cause of chronic liver conditions, is now approximately 7.6% in the general population of children under the age of 19; in obese children, this percentage is as high as 34.2%.12 Treatment protocols addressing NAFLD include dietary intervention and lifestyle modification. Additional targeted nutritional and drug therapies are often added as well, including those that address fat processing by the liver, insulin sensitivity, cholesterol lowering, and antioxidant support. Omega-3 fatty acids may play a significant role in addressing issues associated with NAFLD since these fatty acids control key pathways involved in liver fat metabolism.

A recent 12-month double-blind placebo-controlled trial investigated the effects of omega-3 fatty acid supplementation in 138 obese children with NAFLD.13 Led by Mehmet Boyraz from Turgut Özal University in Turkey, the study involved two groups of children aged 9-17. The placebo group received a recommended reduced-calorie diet (a reduction of 25-30 calories/kg body weight per day) and lifestyle intervention (one hour of exercise three times per week) plus the placebo supplement. The second group underwent the diet and lifestyle interventions along with supplementation of 1,000 mg of omega-3 fatty acids daily.

BMI significantly decreased in both groups. The omega-3 intervention group, however, experienced the greatest benefits. This group saw a greater decrease in BMI, for instance (an average reduction of 6.0 kg/m2 with omega-3s compared to a 3.6 kg/m2 reduction in the placebo group). The omega-3–supplemented subjects also had significantly better HDL cholesterol and triglyceride levels, as well as fasting insulin levels, versus the placebo group. Fasting glucose levels and insulin sensitivity were significantly improved with the omega-3 intervention.

Reductions were found in liver enzyme values in both groups, with more pronounced reductions evident in the omega-3 group. Nearly 68% of those in the omega-3 group had decreased frequency of a fatty liver on ultrasound, while only 40.3% of the placebo group experienced the same decrease.

These results suggest that omega-3 supplementation is a useful intervention, along with dietary and lifestyle modifications, to support the health of children with NAFLD.


Plenty of Promise

Because of the numerous ways in which omega-3 fatty acids impact both structural and biochemical processes in the human body, they remain one of the most unique natural therapeutics for promoting health. With research on certain conditions just beginning, omega-3 fatty acids may one day prove to provide valuable benefits unsurpassed by other natural compounds.



Also read:

AREDS2 Trial: Omega-3s Don’t Benefit Cognitive Health?

2016 Omega-3 Market Update: Fish Oil, Krill Oil, Astaxanthin, and More

“Mixed Results” of Omega-3s for Cardiovascular Health in New Government Report

Re-Esterified Omega-3s May Offer Benefits for Dry Eyes




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  2. Jiang J et al., “Effect of marine-derived n-3 polyunsaturated fatty acids on major eicosanoids: a systematic review and meta-analysis from 18 randomized controlled trials,” PloS One. Published online January 25, 2016.
  3. Zanetti M et al., “Omega-3 polyunsaturated fatty acids: structural and functional effects on the vascular wall,” BioMed Research International. Published online August 2, 2015.
  4. Huang T et al., “Effect of vitamin B-12 and n-3 polyunsaturated fatty acids on plasma homocysteine, ferritin, C-reaction protein, and other cardiovascular risk factors: a randomized controlled trial,” Asia Pacific Journal of Clinical Nutrition, vol. 24, no. 3 (2015): 403–411
  5. Hoffman DR et al., “Impaired synthesis of DHA in patients with X-linked retinitis pigmentosa,” Journal of Lipid Research, vol. 42, no. 9 (September 2001): 1395–1401
  6. Hoffman DR et al., “Four-year placebo-controlled trial of docosahexaenoic acid in X-linked retinitis pigmentosa (DHAX trial): a randomized clinical trial,” JAMA Ophthalmology, vol. 132, no. 7 (July 2014): 866–873
  7. Hoffman DR et al., “ Docosahexaenoic acid slows visual field progression in X-linked retinitis pigmentosa: ancillary outcomes of the DHAX trial,” Investigative Ophthalmology and Visual Science, vol. 56, no. 11 (October 2015): 6646–6653
  8. Haghiac M et al., “Dietary omega-3 fatty acid supplementation reduces inflammation in obese pregnant women: a randomized double-blind controlled clinical trial,” PloS One. Published online September 4, 2015.
  9. Carlson SE et al., “DHA supplementation and pregnancy outcomes,” American Journal of Clinical Nutrition, vol. 97, no. 4 (April 2013): 808–815
  10. Grosso G et al., “Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials,” PloS One. Published online May 7, 2014.
  11. Duffy SL et al., “The effect of 12-wk Ω-3 fatty acid supplementation on in vivo thalamus glutathione concentration in patients ‘at risk’ for major depression,” Nutrition, vol. 31, no. 10 (October 2015): 1247–1254
  12. Anderson EL et al., “The prevalence of non-alcoholic fatty liver disease in children and adolescents: a systematic review and meta-analysis.” PloS One. Published online October 29, 2015.
  13. Boyraz M et al., “Long-term treatment with n-3 polyunsaturated fatty acids as a monotherapy in children with nonalcoholic fatty liver disease,” Journal of Clinical Research in Pediatric Endocrinology, vol. 7, no. 2 (June 2015): 121–127
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