Marine Omega-3 Fats and Mental Health

Since the advent of biological psychiatry research, the principal focus of inquiry has been, and continues to be, abnormalities in the various neurotransmitter systems and their various regulatory proteins. Accordingly, we have the dopamine hypothesis of schizophrenia and the monoamine hypothesis of depression. However, despite many years of research, our understanding of even basic mechanisms of psychiatric disease is limited. Are we even looking in the right place?

While proteins (e.g., transporters, receptors, messenger systems) and neurotransmitters are indeed responsible for the day-to-day running of the brain, their functioning is hugely dependent on the state of the lipid membranes in which they are embedded. Half the dry weight of the brain is lipid and half of the lipid portion consists of essential fatty acids (EFAs).Yet it is only relatively recently that brain lipids have received attention in international research. In light of the ever increasing burden of mental illness, as well as alarming data on how the modern diet is deficient in omega-3 (n-3) EFAs, such research is urgently warranted.

After a look at the basics of EFAs, it is important to understand how changes in the modern diet have affected the balance of n-3 to omega-6 (n-6) EFA, and then to review the known cerebral functions of EFAs. Also, there is compelling literature on common psychiatric disorders in relation to EFAs from the standpoints of epidemiology, mechanistic studies and supplementation trials.

The EFA Balancing Act

EFAs obtained exclusively from diet are a family of long-chain polyunsaturated fatty acids (LC-PUFAs), which are divided into two groups: n-3 (principal sources: fish and seafood) and n-6 (principal sources: vegetable oils).The parent n-3 and n-6 EFAs are alpha-linoleic acid (ALA) and linoleic acid (LA), respectively. These are then enzymatically processed into other LC-PUFAs. The principal neuronal EFAs are arachidonic acid (AA, n-6), docosahexaenoic acid (DHA, n-3) and eicosapentaenoic acid (EPA, n-3). As the in vivo ability of human species to convert ALA into EPA and DHA is limited, estimated at only an 8-percent conversion rate of ALA in one review,1 dietary guidelines recommend the consumption of fish, whose oil is rich in EPA and DHA.

Since the industrial revolution, there has been a dramatic increase in the amount of fat consumed by most people; but, more pointedly, there has been a huge increase in n-6 EFA intake. This relates to the surge in the use of omega-6-containing vegetable oils (e.g., olive, soy, sunflower) as well as the increased consumption by humans and farm animals of cereal-based foods. The latter affects the entire food supply. For example, a free-range egg contains an approximately 1-to-20 n-3-to-n-6 ratio; in battery (caged) eggs, this ratio is closer to 1-to-1.2 Importantly, the data for cultured/farmed vs. wild fish is similar. Although the amount of n-3 EFA has changed little, the pre-modern n- 3-to-n-6 ratio of 1-to-1 has now become 1-to-20. Since both n-3 and n-6 EFAs compete with the same cellular transport and membrane integrative mechanisms, such a dramatic change in ratio implies a similarly large reduction in the amount of n-3 EFA incorporated into the cellular membrane, as well as an n-3/n-6 mismatch in the body in general.3

In the brain, the principal function of the LC-PUFAs is to enhance the functionality of the neuronal membrane by decreasing microviscosity. This has the effect of enhancing the movement of the various regulatory proteins and neurotransmittersresponsible for all forms of cellular activity, including impulse transmissionin and around the membrane in which they are embedded. Secondary functions include roles in neurite growth and controlling inflammatory processes.

It appears that the n-3 EFAs are the most important subtype of LCPUFAs with respect to promoting optimal neuronal function. They are associated with the lowest (optimal) level of neuronal microviscosity, they promote anti-inflammatory pathways, and they have recently been shown to dramatically promote neurite growth.4 The extensive literature of animal supplementation studies supporting a crucial role for n-3 EFAs includes a paper demonstrating a fourfold increase in serotonergic release from the hippocampus following a fenfluramine challenge in rats supplemented with n-3 EFAs.5 Serotonergic function has particular relevance to mental health. Another recent study demonstrated a 40-percent reduction in plaque numbers in an Alzheimer mouse model.6

EFAs and Psychiatric Disorder

There are a number of reports in the literature linking low consumption rates of n-3 food sources and high prevalence rates of depression, bipolar disorder and impulse disorder-related phenomena such as suicide and homicide. One such study from The Lancet demonstrated the documented 60-fold variation between countries in the annual prevalence of major depression is strongly inversely correlated with national fish consumption figures.7 No relationship between fish consumption and schizophrenia has been demonstrated, however.

Decreased levels of n-3 EFAs in subjects with psychiatric disorders have been quite consistently demonstrated. In addition to disorders of the affective spectrum, schizophrenia and, more recently, patients with deliberate self harm/parasuicide have been shown to have lower n-3 EFA levels compared with controls,8 even in studies controlling for estimated dietary intake.This latter point is important, as it suggests that certain populations may absorb or metabolize EFAs differently.

Finally, and offering the most direct line of supporting evidence for a role for n-3 EFAs in mental health, there are a number of randomized, controlled supplementation studies that have demonstrated significant clinical improvement in mental health. For example, our group is shortly to publish data from a 12-week supplementation study in patients with recurrent deliberate self harm.9 Even though all patients in this challenging clinical population received intensive psychiatric input, those on active treatment (EPAX 5500, supplying 1.5 g/d EPA, 1.0 g/d DHA) reported highly significant reductions in depression, perceived stress and suicidal thoughts. This study is hampered by its small sizea feature it has in common with all of the other studies in this area; hopefully, such positive findings will generate sufficient grant support to carry out larger-scale studies.

A final point of relevance to those involved in the marketing of n-3 products is that they appear not just to benefit the mentally ill, but to improve the mental well-being of normal people. In one recent placebo-controlled study, 33 normal individuals reported significant improvement in a battery of measures of well-beingincluding mood, anger and fatiguefollowing 70 days n-3 supplementation.

Malcolm R. Garland is the consultant psychiatrist and senior lecturer at the Royal College of Surgeons in Dublin, Ireland. He can be contacted at [email protected].

Click here for a list of references.