The Study

The EPOCH trial is a randomized, double-blind study assessing the influence of long-chain omega-3 fatty acids on mental faculties and contentment in healthy elderly people.


Nutrition and living habits that are ideal can help to lower the possibility of having a disability, sustaining physical and mental faculties, as well as improving the overall quality of life for both genders. Therefore, these are major determinants of healthy aging . The declining levels of nutrients that come with age, as well as the decrease in absorption and metabolism of those nutrients, can lead to nutritional deficiencies. Particular nutrients, such as omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), may have a positive impact on elderly people and the population as a whole by lessening and avoiding medical problems and death.

It is fascinating to note that people who generally follow the Western diet consume about 10 times more omega-6 polyunsaturated fatty acids than omega-3 polyunsaturated fatty acids. Vegetable oils that have been altered during refining are the main source of omega-6 Polyunsaturated Fatty Acids, which are commonly present in packaged goods.

Within the past one and a half centuries, a rise in the eating of omega-6 fatty acids has been seen while the ingestion of omega-3 has declined, related to a boost in circumstances of heart illness. It was discovered that a ratio of omega-6 to omega-3 fatty acids in the diet would be optimal. According to some scientists, the best supplementation rate for omega-6 to omega-3 fats is two to one; however, the specific proportion that correlates to a decreased chance of heart issues has yet to be found. Experts are now proposing that exact amounts of intake are more significant than the ratio of these amounts. Additionally, both omega-6 and omega-3 fatty acids contend for the same enzymes (delta-4, 5, 6 saturase, and elongase) that transform fatty acids into their active biological states. An even-keeled diet should be low in vegetable oils and high in omega-3. A research project carried out in the past showed that a diet plentiful in omega-3 fatty acids is both beneficial and safe; the researchers proclaimed a small amount of heart disease in the persons of the Eskimos, who ate items loaded with long chain polyunsaturated fatty acids. Studies were carried out to confirm the heart-protecting properties of polyunsaturated fatty acids.

The omega-3 LC-PUFA set consists of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and the less common docosapentaenoic acid (DPA). All three acidic compounds are created from alpha-linolenic acid (ALA). Once ALA is ingested by a human, it is transformed into eicosapentaenoic acid (EPA) 20:5ω3 (which only occurs 1-10% of the time) and, less often, to docosahexaenoic acid (DHA) 22:6ω3 (which is seen 0.5-5% of the time). It is likely that estrogen has an impact on the elevated conversion rate seen in women. In addition, there are genetic variations, although the data accessible is rather limited; APOE and FADS rank among the most significant genotypes. Turning something into something else is apt to be decreased in such circumstances like insulin resistance, which is highly connected with growing older.

A variety of plant-based foods contain both LA and ALA, including walnuts, corn, purslane, spinach, soybeans, safflower, sunflower, pumpkin seeds, and other varieties of seeds like flax, hemp, and chia. These two fatty acids are also present in certain animal-based fats. The capacity for humans to convert linoleic acid (18:2ω6) and ALA (18:3ω3) into long-chain (≥C20) PUFAs is extremely low. Even though Omega-6 Polyunsaturated fatty acids are frequently seen in the food we consume, the overall intake of Omega-3’s, especially by those of older age, is substantially low. An imbalance between omega-6 and omega-3 makes taking omega-3 supplements a secure and beneficial choice for maturing well. There is a double bond situated three carbon atoms away from the methyl termination when it comes to Omega-3 PUFAs. Arachidonic acid is created through the LA pathway using gamma-linolenic acid (18:3ω-6) and dihomo-gamma-linolenic acid (20:3ω-6) as stepping stones. AA interacts with buoyant oxygen via cyclooxygenase, lipoxygenase, and cytochrome P450 processes, causing the creation of eicosanoids, comprising of prostaglandins, thromboxanes, and leukotrienes- significant regulators of the irritation reaction. Most of the AA which is released gets quickly added back into the membrane lipids, thus reducing its availability for oxidation.

The EPA and DHA have impacts that are advantageous over a lot of metabolic operations, like those that assist in lowering serum triglyceride and blood sugar levels, curbing platelet merging, controlling an inflammatory response, aiding the working of the vascular endothelium and progressing the functioning of the heart, brain and immune system.

Fish and other forms of seafood are the primary dietary source of omega-3 long-chain polyunsaturated fatty acids. Fish species including herring, sardines, tuna, trout, and salmon are especially high in omega-3 polyunsaturated fatty acids. Nursing mothers provide the milk, ocean animals such as whales and seals offer the marine mammal variety, and the sea’s plants, like algae, and tiny crustaceans, like krill, are also sources. Elderly people usually need to take supplements since it is usually difficult for them to get enough omega-3 through diet alone. The ESFA panel determined in 2012 that even with up to 5 g of EPA and DHA consumed each day, no safety issues would arise for adults. Omega-3 PUFAs could demonstrate cardiovascular advantages, which include decreasing blood lipids, avoiding blood clots, lowering blood pressure, preventing irregular heart rhythms, and reducing inflammation. Conclusively, experts in science have seen omega-3 PUFAs as possibly vital nutrients for advancing through life well. In addition, the Omega-3 Index (the sum of EPA and DHA in blood cells’ membranes) has been accepted as a measure of the possibility of coronary heart disease and is given as a ratio of total fatty acids. It is best to have an Omega-3 Index of 8% or higher. This level has the highest level of protection, while an Index of 4% or lower has the lowest.




The United States Food and Drug Administration has declared that omega-3 supplements which include EPA and DHA are secure to take as long as the suggested dosage does not exceed 3 g/d. The European Food Safety Authority states that adult intakes of up to 3 to 5 grams of EPA + DHA per day from nutritional supplements are non-toxic in the long run. There is no cause for alarm when adult consume an extra 1.8 grams of EPA (eicosapentaenoic acid) daily. Nevertheless, the unfavorable impacts can include bleeding episodes, weakened immune system, hampered lipid and sugar metabolism, and a higher level of lipid oxidation. Mounting proof suggests that both EPA and DHA have both unique and common effects.

EPA, DHA, and DPA are distinct in terms of their biochemical makeup and the way they are metabolized. DHA is the most significant omega-3 polyunsaturated fatty acid in the brain, and research has demonstrated that it has a noteworthy effect on the neuronal membrane. DHA is beneficial for protecting neural health and is essential for keeping the brain functional and sharp in maturity, as well as aiding in cognitive development. It appears that EPA is a more accurate marker of omega-3 PUFA intake than DPA and DHA likely because of the dissimilar methods by which it is interjected into membrane phospholipids. The concentration of EPA in the body is primarily determined by its exchange with plasma lipoproteins while the presence of DPA and DHA are generally found in the inner membrane and their amounts in the system are largely affected by red blood cell turnover.

The results of a consolidated evaluation of different research indicated that EPA was responsible for lessening the risk of death from heart conditions, as well as helping with depression, rather than DHA or DPA.


A number of investigations indicate a potential relationship between omega-3 long-chain polyunsaturated fatty acids (n-3 LC PUFAs) and enhanced cognitive performance in senior citizens. Up to this point, only two different controlled, randomized trials have looked at the impact of n-3 LC PUFA supplementation on the mental abilities of elderly people who show no signs of cognitive decline. Of these tests, only one showed an advantage for individuals who had the ApoE-ε4 gene. It is still not understood how taking n-3 LC PUFA supplements affects how well the brain functions in older people who are generally healthy. The primary intent of this research was to look into the possibility of n-3 LC PUFAs delaying cognitive handicaps in elderly, accounting for ApoE-ε4 allele ownership as a potential mediator. The detailed methodology of the trial is reported herein.





The goal of this investigation was to determine over an 18-month time period if a product containing DHA-rich fish oil could have a beneficial effect on delaying the mental decline experienced by elderly people with no forms of dementia. It was predicted that the group which received n-3 LC PUFA supplementation would experience a slower decline in cognitive faculties than the group that did not take the supplement. The research was conducted to investigate how nutrition, well-being, and lifestyle choices can lead to improved mental and physical health in the elderly population, both at present and in the long term.

The main purpose of the study was: 1) to evaluate the connection between intake of n-3 LC PUFA and cognitive performance at the start; 2) to understand if taking n-3 LC PUFA supplements diminishes cognitive decline moderated by ApoE-ε4 allele, initial cognitive status, and measures of n-3 LC PUFA intake; 3) to look into the impact of the intervention on functional capacity and contentment; and 4) to study the relationship between intake of n-3 LC PUFA and functional capacity and contentment initially.

This paper provides information about the approach that was taken in the investigation, such as the plan, evaluation tools, and the procedures followed.

Study Design

This study was an 18-month long experiment in which participants were randomized into groups and neither they nor the researchers knew who was receiving the placebo or the actual treatment. Measurements were taken every 6 months, making a total of 4 times the data was collected. By having multiple instances of measuring the changes over time, the rate of changes can be established and the impact of an intervention can then be evaluated not just in one moment, but through its progression. This is due to the fact that the main hypothesis surrounding change is part of a continual development process. The deterioration of brain abilities prone to the effects of getting older typically begins in the early 30s, so despite the fact that all individuals were tested to check their cognitive skills, everybody was assumed to experience a decrease of mental capability to a certain point. For example, studies of data from people of different ages indicate on average that processing speed decreases by around 20% by 40 years old and by 40-60% at age 80. Studies have shown that using n-3 PUFA supplements over a period of three to four months can produce important cognitive benefits. Studies on clinical populations illustrated rapid changes, though this level of effect might not be expected in a normal population. A longer period of multiple tests was implemented in order to best assess the hypothesis, affording more power to detect the impact.

The research was managed from CSIRO Food and Nutritional Sciences, situated in Adelaide, Australia. The details of the protocol were outlined to the participants, and all of them gave their written consent before the study began. The Human Research Ethics Committee of CSIRO gave their consent for all of the experimental activities to be carried out, in line with the guidelines stated in the Helsinki declaration. The study follows Good Clinical Research Practice. The study’s research officer urged people taking part in the investigation to inform them of any negative occurrences that happened; these were then documented by the officer. The trial clinical doctor was informed of negative reactions believed to have been caused by the taking of dietary supplements. These were monitored accordingly. The individuals who took part visited the facility every few months – every 6 months to have their assessments done and 3 months afterwards to receive more capsules and be monitored. At each of these appointments, information was logged about any unfavorable events that happened, any changes to drug or supplement utilization, or overall health.

Participant Recruitment

Sampling and Criteria

People were chosen to take part in the study from the greater Adelaide region in South Australia by calling on resources of organizations for elderly people, through releasing advertisements and through news announcements. Answers to inquiries of interest were disseminated in the form of datasheets outlining the specifics of the experiment and requesting participation from volunteers. In order to qualify for the study, participants had to be between the ages 65 and 90 at the beginning, must be able to communicate in English, and must agree not to begin taking n-3 fish-oil (or algal) supplements during the trial. Individuals who were using n-3 fish-oil (or algal) supplements, had experience with any illness that has been proven to lead to mental issues (i.e., head injury, other brain trauma, transient ischemic attacks, stroke, coronary artery bypass surgery, open heart surgery, degenerative neurological disorder, history of abusing drugs/alcohol), were taking medicine that hampers cognitive skills, had a severe disease, were diagnosed with an intellectual handicap, had a major episode of clinical depression, diabetes or any form of dementia, or scored below 22/27 on a telephone-administered version of the Mini-mental State Examination (MMSE) (which stands for lower than 24/30 on the standard MMSE, which is the traditional cutoff for potential dementia), were excluded from study entrance.


This paper gives a thorough description of a double-blind, randomized controlled experiment to analyze the effectiveness of an DHA-enriched fish-oil supplement at delaying cognitive deteriorating, for 18 months, among cognitively fit elderly individuals. This study is one of the few research efforts so far that have studied the effects of n-3 LC PUFA supplementation on the reduction of intellectual decline in elderly individuals who are not suffering from any form of cognitive impairment. The current research has a wide array of benefits, including a full-scale evaluation of brain activity and data collected across multiple time points. This allows the assessment of the treatment’s impact over a period of time rather than the effect at a particular moment. The potential implications for society could be massive if this ready and affordable dietary approach has the capacity to safely lessen mental deterioration as people age, considering how these issues are attached to the individual and communal responsibility of dependence and poorer quality of life as one gets older.





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