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Maximizing Omega-3 Health Benefits

June 2014

By S.R. Knowlton

Maximizing Omega-3 Health Benefits  

There are now close to 20,000 published studies on the benefits of omega-3 fatty acids. As researchers continue to discover new longevity mechanisms such as reducing brain shrinkage, protecting memory and improving endothelial function, scientists have begun to analyze how different omega-3 sources affect the body.

Emerging evidence suggests that omega-3s from fish oil as well as krill oil, provide complementary effects upon different cellular targets.1 In addition, scientists are finding that cellular uptake of omega-3 fatty acids from fish and krill oil occur at different rates depending on their destination.2

Intriguing data suggest that combining fish oil and krill oil may provide enhanced support for cardiovascular health and the nervous system, including the brain. This is due to the different levels and rates of uptake observed for omega-3 fatty acids from fish and krill oil in plasma, platelets, and red blood cells.

As scientists continue to study uptake of marine oils into various cells and tissue components in the body, the evidence suggests that by combining both fish and krill oil, you may optimize the protective benefits provided by these different sources of omega-3 fatty acids.

What you need to know

  • Omega-3-rich oils from deep-sea fish have long been known to provide outstanding anti-inflammatory benefits that can protect you from heart disease.
  • New findings show that these marine oils can also prevent age-related brain shrinkage, protect cognitive function and memory, and prevent dementia and possibly depression.
  • Another marine oil, extracted from tiny crustaceans called krill, provides additional benefits not found in fish oil alone.
  • Emerging research suggests intriguing pharmacodynamics and pharmacokinetic differences for omega-3 fatty acids bound to phospholipids (such as in krill oil) as well as fish oil, which offer differential advantages to the cardiovascular and nervous system/brain.
  • Krill oil has benefits that add to and amplify those from fish oil alone, in neuroprotection, cardiovascular health, diabetes, obesity, metabolic
syndrome, and even osteoporosis and arthritis.

Benefits Of Both Fish Oil And Krill Oil

Fish oil and krill oil share many important similarities, such as effectively reducing the ratio of omega-6 to omega-3 fatty acids in the body. This is an important biomarker associated with lower levels of chronic inflammation.2 Both krill and fish oil also increase plasma and cell membrane concentrations of omega-3 fats.3.4

However, there are differences. What scientists have found is that the uptake of omega-3 fatty acids from fish oil and krill oil is different for the plasma, platelets, and red blood cells.5

For example, clinical data from human test subjects suggest that omega-3 fatty acids like DHA from fish oil result in a more rapid uptake into plasma triglyceride and platelet phospholipids,6 which offers benefits given the effects of plasma triglycerides and platelet function on endothelial function, and cardiovascular health in general.

In comparison, the omega-3s found in krill appear to be more rapidly incorporated into red blood cell phospholipids.7 This is important, because not only do scientists view the uptake of essential fatty acids in red blood cells as a biomarker for uptake into the brain,8 but additional research suggests that when omega-3 fatty acids such as DHA are bound to phospholipids as they are with krill, it increases their uptake to the brain.9 This is further supported by human clinical research, which suggests ingestion of phospholipid-bound EPA and DHA increase cognitive function scores to a greater degree compared with scores obtained when the fatty acids in the ingested oil were provided in the triglycerides storage form.10

When combined, krill and fish oil appear to offer enhanced benefits for both the cardiovascular and nervous system than either form by itself.

Let’s now look at how fish oil and krill oil work together to provide the broadest spectrum of coverage for brain health, heart health, and much more.

Omega-3s And Brain Health

Omega-3s And Brain Health 

Both omega-3 fatty acids DHA and EPA are well known to provide systemic benefits throughout the body and reduce the risk of early death.11

DHA is vital for early brain development and maintenance, while EPA seems to be closely related to behavior and mood. Together, both molecules provide critical neuroprotective benefits.11 These neuroprotective effects are important for the prevention of age-related brain shrinkage (cortical atrophy). Aging adults with brain shrinkage often experience memory loss, cognitive decline, and an increase in depression.12-14

Studies show that people with higher levels of omega-3 fatty acids in their blood experience brain benefits such as better cognitive outcomes, larger gray matter volume for their age, fewer signs of brain blood flow disturbances, and lower rates of dementia, compared with those having lower omega-3 fatty acid levels.15-20

Those with lower DHA levels have poorer scores on cognitive testing, smaller brain volumes, and more “white matter hyperintensity” (also called leukoaraiosis), a condition that is associated with accelerated brain aging.21

One important way omega-3 fatty acids protect your brain is by shielding the chief memory processing area of your brain, the hippocampus. Studies show that people with lower total omega-3 levels have smaller hippocampus volumes.22

Because patients with depression experience rapid shrinking of their hippocampus, many strategies for relieving depression focus on increasing new brain cell growth in that specific area of the brain.23 There’s now evidence that increasing omega-3 intake, especially DHA, may be an effective way of treating or preventing depression, partly by protecting the hippocampus from further shrinkage.23

In addition to depression, chronic stress leads to loss of volume of the hippocampus—and also causes enlargement of the amygdala, the portion of the brain that regulates anxiety and anger.24 When rats were supplemented with omega-3s during exposure to stress, they showed lower corticosterone levels (a marker of stress), and improved learning on a maze—indicating that the omega-3s helped preserve memory and reduce anxiety.24

Diabetes is a key factor in accelerated brain aging. Neuroprotective and cognition-improving effects have been shown in diabetic animals when they were supplemented with omega-3s.25

Omega-3s are also credited with slowing the rate of cognitive decline in patients with very mild early Alzheimer’s disease. This study demonstrates the importance of early intervention with omega-3s for aging adults.26

Krill Oil’s Additional Brain Benefits

Both krill and fish oil are rich in the long-chain fatty acids EPA and DHA.

An important difference, however, is that EPA and DHA found in krill oil are bound to phospholipids, a form of fat that makes up the cell membrane. Phospholipids also enhance cell signaling, which is especially important for the healthy functioning of the nervous system and the brain.

Studies show that when omega-3 fatty acids such as DHA are bound to phospholipids as they are with krill, it increases their uptake to the brain.27

In lab experiments, animals given krill showed improved navigation skills. What this means is that they achieved higher levels of cognition and memory required to navigate complex territory.28 In addition, research shows that animals supplemented with krill oil showed significantly fewer signs of depression and resignation. This improvement in mood was equivalent to the effect of the prescription anti-depressant drug imipramine (Tofranil®).29

Human studies also confirm cognition and memory improvement with omega-3 supplementation. For example, a study showed that both fish oil and krill oil enhanced cognitive function in a group of older men by increasing oxygen delivery to their brains. Interestingly, for those taking krill oil this effect was more prominent than those taking fish oil, though both groups were significantly better than placebo.30 As we pointed out earlier, because the omega-3 DHA is bound to phospholipids in krill it may be more effectively incorporated into the critical cell membrane in brain cells.

Enhanced Cardio Protection With Fish And Krill Oil

It has long been known that higher levels of omega-3 fatty acids like EPA and DHA are strongly linked to improved cardiovascular health; while lower levels of omega-3s in the blood are linked to increased rates of hypertension and risk of heart attack. That association continues to grow stronger in a host of heart disease-related areas.

Ample evidence from animal studies supports regular supplementation with omega-3 oils as a means of lowering long-term cardiovascular risk. This may be due to omega-3 fatty acids’ effects on reducing inflammation, lowering triglycerides, reducing blood pressure, improving endothelial function, inducing new blood vessel formation after heart attack or stroke, and favorable modification of obesity-related inflammatory molecules.35-39

Human clinical trials also abound demonstrating the benefits of omega-3s for heart health. Here are a few highlights:

  • Taking 4 grams per day of a prescription EPA supplement led to marked reductions in plasma triglyceride levels, especially in people with very high levels; reductions of 33 to 45% have been reported.40-42
  • Similarly, 4 grams per day of prescription EPA led to significant reduction in triglycerides and other dangerous lipids in people already on statin-type lipid-lowering medications.43,44
  • Taking 4 grams per day of prescription EPA led to significant reduction in oxidized LDL-cholesterol and C-reactive protein (CRP), measures of oxidation and inflammation, respectively.45  
  • In patients with cardiac complications from metabolic syndrome, taking 1,440 mg/day of omega-3 fatty acid supplements led to improvements in endothelial function, including improved blood flow resulting in vessel dilation.46
  • Taking 520 mg/day of DHA and 120 mg/day of EPA led to decreased platelet aggregation (clot-forming).47
  • In obese adults, 4 grams per day of a 46% EPA, 38% DHA supplement, and diet changes led to increases in both large and small artery elasticity.48
TABLE: Impact Of Omega-3 Status On Cardiovascular Risk


Omega-3 Measure

Difference in Risk

Complex Coronary Lesion (high risk for heart attack)

Low ratio of EPA to arachidonic acid (Arachidonic acid is a source of inflammatory mediators)

110% higher risk with low EPA31


Higher phospholipid omega-3 level

57% lower risk with higher phospholipid omega-3 level32

Atrial Fibrillation (heart arrhythmia)

Higher total omega-3 level

29% lower risk with higher total omega-3 level33

Risk of hospitalization for heart failure after heart attack

Low EPA level

140% higher risk with low EPA level34

Additional Heart Health With Fish Oil

Additional Heart Health With Fish Oil 

Both fish oil and krill oil are rich sources of heart-healthy omega-3 fatty acids. However, fish oil may provide advantages for cardiovascular health beyond those found in krill oil.

An interesting human study directly compared the ingestion of phospholipid-bound DHA found in krill with the form of DHA naturally found in fish oil. The results showed that the DHA found in fish oil was absorbed much quicker than the phospholipid-bound DHA uptake into plasma from krill by almost 3-fold.49

This data has important implications and suggests that the form of DHA found naturally in fish oil provides a more rapid uptake into plasma triglycerides, as well as platelet phospholipids, both of which are important considerations for optimizing cardiovascular health.

The omega-3 fatty acids found in krill oil and bound to phospholipids provide additional cardio- vascular benefits, as you will see in the next section.

Heart Benefits From Krill Oil

To these impressive heart health findings on fish oil, we can now add complementary cardiovascular benefits from krill oil.

Laboratory studies in rats showed that krill oil reduced harmful triglyceride concentrations in the liver more than the fish oil.50-53

Krill oil was able to reduce structural and molecular changes found in the hearts of rats after a heart attack. After the heart attack, only the rats supplemented with krill oil were observed to have a significant reduction in heart weight, inflammation, and left ventricle dilation as compared to controls.54

Omega-3 Fights Metabolic Syndrome And Diabetes

People with metabolic syndrome (the combination of central obesity, high blood pressure, disturbed lipid profile, and impaired glucose tolerance) are at increased risk of death from cardiovascular disease, diabetes, cancer, and other apparently “age-related” disorders. Because metabolic syndrome is closely associated with chronic low-grade inflammation, the powerful anti-inflammatory effects of omega-3 fats are especially important as a means of slowing or stopping the progression of this deadly disorder.

Studies indicate that supplementing with omega-3s can reduce various factors involved in the metabolic syndrome. The following is a list of the benefits of supplementing with omega-3s to reduce the impact of metabolic syndrome:

  • Reduces body weight55,56
  • Lowers blood pressure55
  • Normalizes lipid profiles (lowering LDL, total cholesterol, and triglycerides)55,57
  • Reduces fasting and after-meal glucose and insulin levels while improving insulin sensitivity,38,56-60 and
  • Reduces total body inflammatory status, as measured by elevated cytokines and other markers of inflammation such as C-reactive protein.55,57,61,62

An exciting animal study recently showed that, in diabetic rats, DHA supplementation not only helped to prevent diabetic eye disease, but also increased the survival rate of animals by around 25%, compared with the diabetic rats supplemented with soybean oil.63

Krill Oil And Weight Loss

Animal studies show potent reduction of liver fat stores, glucose levels, and cholesterol levels in mice supplemented with krill oil while being fed a high fat diet.64,65 While many of these effects are seen with fish oil as well, studies show that krill oil, with its unique phospholipid structure, had the added benefit of increasing fat-burning in mitochondria while reducing new glucose production in the liver.66,67 As with so many other complex disease processes, utilizing multiple pathways to reduce disease is a highly effective strategy.67

Synergy In Bone And Joint Health

Synergy In Bone And Joint Health  

People used to believe that osteoporosis and osteoarthritis were the result of aging and reduced intake of calcium and milk products. Science has now shown that these bone and joint disorders are, in part, due to inflammation. Because of this, bones and joints are prime targets for the anti-inflammatory properties of omega-3 oils from both fish and krill.

In both animal and human studies, omega-3s from fish oil have been found to reduce post-menopausal bone loss.68-71 This effect appears to be related mainly to a decrease in the number and activity of bone-destroying cells, due to reduced inflammation because of increased levels of omega-3s.72-77

On the other hand, people with lower blood levels of omega-3s are more likely to experience arthritis-related cartilage loss, compared to those with higher levels.78

And in osteoarthritis, when a DHA/EPA formulation was added to chondroitin sulfate, people experienced more complete relief of symptoms such as stiffness and pain. One study found a significant increase in walking speed in people who supplemented with fish oil versus those who did not.79,80 As with the beneficial results seen in people with bone loss, these positive findings may have been the result of the decreased inflammatory destruction of joint cartilage.81

In arthritis-prone guinea pigs, omega-3 supplementation significantly reduced the occurrence of the disease. In addition, omega-3 supplementation in osteoarthritic dogs and cats led to increased levels of daily activity.82-84

Krill oil is joining the toolkit for fighting arthritis, thanks to its exceptional anti-inflammatory properties resulting from its phospholipid form of omega-3s. A study in mice with experimental arthritis showed that krill oil supplements reduced arthritis scores and markedly diminished joint swelling. When examined under a microscope, the animals’ joints were remarkably free of inflammatory infiltrates of immune system cells.85

A study on humans has also shown the benefits of krill oil on arthritis.86 In a double-blind, randomized, placebo-controlled study, 90 patients who had cardiovascular disease and/or rheumatoid or osteoarthritis along with high levels of C-reactive protein (CRP, an indicator of inflammation), received either 300 mg/day of krill oil or placebo.

After just seven days, those supplementing with krill had their CRP levels reduced by 19.3%, while in the placebo group, CRP levels rose by 15.7%. Even more impressive, the krill benefit was long-lasting. The krill group’s CRP levels continued to fall by 29.7% at 14 days, and 30.9% at 30 days. More importantly from the patients’ points of view, the krill oil supplement reduced pain scores by 28.9%, reduced stiffness by 20.3%, and reduced functional impairment by 22.8%.