Almost the only natural sources of omega-3 fatty acids are oily marine fish like salmon, herring, mackerel and halibut. In addition, some plant-sourced foods (e.g., rapeseed, soybean and walnut oil) contain the omega-3 fatty acid alpha-linolenic acid (ALA), which the human body is able to convert to some extent to EPA and DHA. Findings from several large studies indicated health-promoting effects and disease-preventive activity of omega-3 fatty acids. However, data, in particular results from studies into the treatment of pre-existing diseases with these macronutrients, is inconclusive. Moreover, many investigations were carried out with participants who were already at increased risk of disease and in some cases already undergoing treatment with medication. The best recommendation for disease prevention appears to be for a long-term, regular intake of omega-3 fatty acids, either from food – e.g., consumption of oily fish once or twice weekly – or as dietary supplements.
Omega-3 fatty acids in the prevention of
Omega-3 fatty acids like long-chain docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) possess extensive anti-inflammatory properties which can support the prevention and treatment of numerous inflam- matory diseases. Interventions center on reducing amounts of omega-6 fatty acid arachidonic acid (AA), from which inflammatory intermediates, i.e., the substances that mediate inflammation, are formed. The recommendation is therefore to reduce the intake of AA, which is found mainly in pork, egg yolk, tuna and liver pâté, whilst simultaneously increasing consumption of omega-3 fatty acids (especially EPA and alpha-linolenic acid), which are AA antagonists. This means consuming more oily marine fish (like salmon, herring, mackerel, sardine and tuna) and plant oils (rapeseed, flax and walnut oil). Omega-3 fatty acids can displace pro-inflammatory AA from some metabolic pathways and hence combat the formation of inflammatory intermediates – like eicosanoids (hormone -like substances, for instance prostaglandin E2) and inflammatory cytokines (regulatory proteins which control the immune response, such as tumor necrosis factor alpha [TNF-alpha] and interleukin-1), as well as C-reactive protein (1-3). Further, several families of lipid media- tors that are formed from EPA and DHA appear to be involved in the resolution of inflammation. These locally active mediators (e.g., resolvin and protectin) act on specific receptors and activate pro-resolving processes in various target cells (4). Moreover, the anti-inflammatory effect of omega-3 fatty acids evidently also derives from their anti- oxidative abilities, inasmuch as they neutralize aggressive oxygen radicals (oxidants) which are also involved in inflammatory processes (5). Overall, these anti-inflammatory properties of omega-3 fatty acids could play an important role in the prevention and treatment of many chronic and acute inflammatory diseases, such as rheumatoid arthritis, chronic inflammatory diseases of the intestines (e.g., colitis ulcerosa and Crohn’s disease), asthma, cancer, atherosclerosis and other cardiovascular diseases, neurodegenerative diseases, autoimmune diseases, inflammation of the gums (periodontitis), and also diabetes, obesity and mental disorders (1, 6, 7).
The increased production of anti-inflammatory mediators from DHA and EPA appears to have a beneficial effect in particular on inflammatory asthma, as well as on rheumatoid arthritis (8, 9). In clinical studies daily administration of on average 3.5 mg omega-3 fatty acids to patients with rheumatoid arthritis showed posi- tive effects such as reduction in pain, swelling, joint stiffness and tiredness, as well as making it possible to reduce administration of standard medications (e.g., non-steroid anti-rheumatic drugs and antiphlogistics), which have many side effects (2). With gum inflammation (periodontitis), one clinical study in which 300 mg omega-3 fatty acids were given daily led to a distinct reduction in inflammation and in the depth of perio- dontal pockets (10). The autoimmune disease multiple sclerosis is a chronic inflammation of the central nervous system (brain and spinal cord), in the course of which a substance called myelin that normally forms a protective sheath around the nerve fibers becomes increasingly damaged. Several studies were able to show that omega-3 fatty acids can combat the inflammatory process and myelin loss (11). Patients with obstructive sleep apnea (when breathing stops during sleep) also experience inflammation, mediated by the cytokine TNF-alpha that can lead to cardiovascular disorders. Blocking the inflammatory processes through consumption of sufficient omega-3 fatty acids could prove beneficial (12). Studies into the preventive effects of omega-3 fatty acids on cancers involving inflammatory processes have not, as yet, delivered any conclus- ive results (13). The most promising indications from epidemiological and clinical studies relate to a redu- ction in the risk of developing prostate cancer through the consumption of adequate amounts of omega-3 fatty acids (14, 15).
The key cause of cardiovascular diseases is atherosclerosis (hardening of the arteries). This occurs when LDL - cholesterol, for instance, accumulates on the lining of the arteries and forms so-called plaques. These can thicken the walls of the blood vessels and cause them to stiffen. Gradually, the arteries narrow, causing a rise in blood pressure. The blood-pressure-lowering properties of DHA and EPA described in various studies could be due to their anti-inflammatory and anti-atherosclerotic activity. An essential factor in the formation of plaques is inflammation of the walls of the blood vessels (endothelium) (16, 17). Both clinical studies and a meta-analysis have shown that increasing consumption of omega-3 fatty acids (e.g., 1 g per day, in the form of either dietary fish or food supplements) could, because of their anti-inflammatory and antioxidant proper- ties, help combat the formation of atherosclerotic plaques and hence lower the risk of developing cardiova- scular diseases such as hypertension (18-20). A randomized controlled study involving patients with meta- bolic syndrome was able to show that administration of 2 g omega-3 fatty acids per day for 12 weeks could reduce the inflammation markers in the blood, improve endothelial function and diminish the degree of arterial stiffness (21).
Like high levels of blood cholesterol, raised concentrations of triglycerides (neutral fats) can encourage the development of atherosclerosis. Omega-3 fatty acids lower triglyceride levels. Further, they have long-term positive effects on blood cholesterol levels: they can positively influence the ratio of harmful LDL and VLDL cholesterol to protective HDL cholesterol in the bloodstream by increasing the share of the latter (22). In particular, patients with metabolic syndrome, who suffer from a disorder of lipid metabolism, blood glucose metabolism (insulin resistance), hypertension and substantial accumulation of abdominal fat (visceral obe- sity) and are therefore at considerably higher risk for coronary heart disease, could benefit from the trigly- ceride-lowering activity of omega-3 fatty acids (23).
Apart from heart rhythm problems (arrhythmia), including irregular heartbeat, palpitations and tachycardia which occur only occasionally and are not connected with a pre-existing heart condition, atrial fibrillation is one of the commonest forms of arrhythmia. Left untreated, atrial fibrillation, which is usually associated with hypertension and cardiac insufficiency, is linked to the risk of stroke, among others. The positive, protective effects of omega-3 fatty acids on the blood vessels could not only help prevent general disturbances to heart rhythm (24) but even help prevent atrial fibrillation and sudden cardiac death (25). According to one meta- analysis, omega-3 fatty acids could also lower the risk of cardiac death by 9% and overall mortality by 5%, especially in people with a high cardiac risk (26).
Research also reveals promising approaches in secondary prevention. In one randomized controlled study involving patients who had suffered a myocardial infarction (heart attack) three months previously, it was revealed that those subjects who took one gram of omega-3 fatty acids a day for three years were almost as effectively protected against another infarction as those patients who were treated with statins as part of a standard therapy (27).
The cardiovascular system reacts with extreme sensitivity to mental stress: the autonomic nervous system raises blood pressure and accelerates the heart rate. Constant tension due to persistent mental stress can damage the heart. Stress management and stress control are already among the most important preventive strategies for disorders of the cardiovascular system. Clinical studies were able to demonstrate, inter alia, that daily intake of a fish-oil product with omega-3 fatty acids (1.6 g EPA and 1.1 g DHA) for eight weeks reduced cardiovascular reactivity to mental stress and hence can reduce the risk to cardiac health (28, 29).
Despite the many positive findings, one recent meta-analysis of several studies into the preventive and therapeutic potential of polyunsaturated fatty acids for coronary diseases highlighted the lack of evidence regarding their health-promoting effects and also questioned current guidelines relating to the consumption of omega-3 fatty acids (3.5 g/day in the USA) (30). Experts criticized that the results of the data analysis, based on studies of varying quality, and the conclusions drawn regarding the influence of omega-3 fatty acids on multifactorial heart diseases – as the only component of a complex lifestyle – were not valid. In the final instance, the analysis showed an approximately 25% reduction in the risk of developing coronary heart disease with higher blood concentrations of DHA and EPA.
A good supply of omega-3 fatty acids to mother and child is essential for the development of healthy eyes prior to birth and in infancy (31). Targeted consumption of docosahexaenoic acid (DHA), in particular, can support this development (32). In the first four to six months of life, especially high concentrations of DHA are stored in the cell membranes of the photoreceptors in the retina and the visual cortex in the occipital lobe at the back of the brain. DHA is thus of crucial importance for the development and maintenance of visual acuity and visual performance. In older age the focus changes to the protective effect of omega-3 fatty acids on blood vessels for the prevention of eye diseases like age-related macular degeneration (AMD). The macula lutea is a yellow-pigmented area in the center of the retina and the “point of sharpest vision”. The yellow pigments (lutein and zeaxanthin) in the macula function almost like sunglasses and protect the eyes from most of the short-wave UV B radiation in sunshine. UV B rays intensify the oxidation and hence destruction of retinal cells over the course of the lifetime. The gradual degeneration of the retinal cells causes loss of focus and blurred vision, and can even lead to the complete loss of visual acuity. Depending on the severity of the damage in the macula, AMD is classed as “dry” or “wet”. Whilst the dry form does not respond to medication, the wet (neurovascular) form, in which abnormal blood vessels develop in the center of the retina, is treated with medication. Otherwise there is a risk that visual acuity will be completely lost within a few weeks or months. The ability of the macula to function is therefore also dependent on the presence of intact blood vessels in the retina. Macular function becomes limited as we age, due to restrictions in blood flow and inflammation of the retina (retinitis pigmentosa). Omega-3 fatty acids can combat inflam- matory processes in the retina (33). The potential for prevention of AMD by increasing the intake of omega-3 fatty acids was demonstrated in several studies, in particular in one large cohort study (34). Moreover, in the cross-sectional observational Age-Related Eye Disease Study 2 (AREDS 2) a dietary supplement which contained the two omega-3 fatty acids docosahexaenoic acid (350 mg/day) and eicosapentaenoic acid (650 mg/day), as well as carotenoids, was found to have a preventive effect on AMD. Other positive evidence was found by the large cross-sectional Twin Study of Age-Related Macular Degeneration in the USA (35). Further, one study showed that increasing the intake of fish and therefore of EPA and DHA could lower the risk of developing dry eyes (sicca syndrome) (36).
Diabetes, a chronic disorder of glucose metabolism, is characterized by high blood sugar levels, increased production of triglycerides and, in the long term, damage to blood vessels. Both type 1 and type 2 diabetes are associated with chronic inflammatory processes and an increased risk of coronary heart disease.
A large epidemiological study of children at increased risk for type 1 diabetes was able to show that the probability of developing the condition was 55% lower in participants with a high intake of omega-3 fatty acids than in participants with a low intake (37). A randomized controlled study with type 2 diabetics showed that administration of 2 g eicosapentaenoic acid daily for three months could reduce the decline in the effect of insulin (insulin resistance) (38). A meta-analysis revealed that omega-3 fatty acid could reduce cardiovas- cular risk factors in diabetics: blood triglyceride levels were lowered by up to 25% and VLDL cholesterol levels by up to 36% (39).
Further, there are indications that omega-3 fatty acids not only help lower raised blood lipid values (trigly- cerides and VDLD cholesterol), but can also help overweight people, who often suffer from disorders of lipid and blood glucose metabolism as well as hypertension, to reduce their weight by preventing the uptake of fats into the fat cells (adipocytes) (40). In one clinical study with overweight young men, subjects given fish oil with omega-3 fatty acids whilst on a calorie-reduced diet lost one kilogram more within four weeks than those subjects who received only a placebo with their diet (41).
Disorders of brain metabolism and brain function
Omega-3 fatty acids are essential for brain and nervous system functioning. Over 30% of the structural fats in the brain consist of docosahexaenoic acid (DHA). The omega-3 fatty acid is responsible for the flexibility and permeability of brain cell membranes and hence also for the rate of communications between the nerve cells (neurotransmission). In addition to DHA, eicosapentaenoic acid (EPA) influences the transmission of messenger substances such as dopamine, noradrenalin and serotonin in the brain. Moreover, DHA and EPA protect nerve cells against the inflammatory activity of the cytokine TNF-alpha (42). Many studies indicate that DHA, as an essential structural and functional building block of the brain, is particularly important for the development of the infant brain. For this reason, a good supply of DHA to the mother during pregnancy and lactation is important. Thus, one controlled randomized study was able to show that children whose mothers consumed 1.1 g EPA and 2.2 g DHA daily during pregnancy demonstrated considerably better hand and eye coordination at the age of 2.5 years than subjects in the placebo group (43).
Later, too, cognitive performance appears to be positively influenced by omega-3 fatty acids. Several clinical studies were able to show an improvement in the symptoms of attention-deficit hyperactivity syndrome (ADHS) with DHA and EPA treatment (44). In one study, children aged between 5 and 12 years with impaired coordinational development who also demonstrated learning and behavioral difficulties showed improve- ments in reading, spelling and general behavior after a three-month treatment with omega-3 fatty acids (45).
One randomized controlled study showed that the quality of sleep in schoolchildren aged between seven and nine years who were given 600 mg DHA daily for four months was considerably improved. They had less difficulty falling asleep, fewer occurrences of parasomnia (sleep disturbances that include nightmares, sleep paralysis and even bedwetting) and fewer sleep disturbances in general (46). Children given DHA slept almost an hour longer per night, and had seven fewer waking phases than children given a placebo. A higher DHA level in relation to the long-chain omega-6 fatty acid arachidonic acid was also associated with fewer sleep problems. It has long been known that diverse substances that are produced in the body from ome- ga-3 and omega-6 fatty acids play a key role in sleep control. For instance, low concentrations of DHA have been associated with reduced melatonin levels. Melatonin is a hormone that plays an important part in the human sleeping and waking rhythm (47). Earlier studies showed that blood DHA levels in the seven- to nine-year-old age range were generally alarmingly low. This could have caused sleep problems which could have expressed themselves in the form of the behavioral and learning problems observed with these child- ren.
Of the psychological disorders, depression was particularly associated with inflammation (48). Consequently, targeted administration of anti-inflammatory substances like omega-3 fatty acids could combat depression. Possible preventive effects are primarily suggested by epidemiological studies (49).
Further, a balanced diet that contains sufficient EPA and DHA can help reduce the risk of neurodegenerative diseases. Many epidemiological studies produced evidence that consumption of fish and higher blood levels of EPA and DHA could be linked to a lower risk of losing cognitive abilities and developing dementia. The most common neurodegenerative disease is Alzheimer’s disease. Specific protein deposits in the brain (beta-amyloid plaques) are characteristic of this condition. Studies were able to show that omega-3 fatty acids, especially DHA, reduce the production of amyloid proteins (50). Moreover, the fatty acids appear to be able to prevent accumulation of these proteins (51). Initial evidence of a possible preventive effect of omega-3 fatty acids in Alzheimer’s, in particular the prevention of initial symptoms in early stages of the disease, came primarily from animal models and epidemiological studies (52, 53).