Omega-3 Fatty Acids and Endocrine/Immune Dysfunction in Humans

Experimental data in animals and in humans suggest that there is an age-related loss of responsiveness of target cells to the hormones and cytokines, which normally regulate their activities. In a few studies this age-related change has been improved by altering the fat content of the cell membrane. This effect may be due to changes in the physical characteristics of the membrane (improved fluidity, reduced viscosity) or to other actions of unsaturated fatty acids.

To understand why this might be, one needs to know how hormones and cytokines work. These chemical messengers are mainly large molecules, proteins and peptides, which cannot cross the cell membrane. Therefore, in order for hormones and cytokines to influence what happens inside the cell, they must transmit a signal across the cell's outer membrane to alter the biochemical activity within the target cell.

 This "transduction" of chemical signals from outside to inside the cell is accomplished via special protein molecules called "receptors," which are imbedded in the cell's outer membrane. One part of the receptor molecule faces outward while another portion is inside, in contact with the cytoplasm. The outer portion of the receptor binds specifically to a particular hormone or cytokine (known generically as a "ligand") because the receptor's 3-dimensional structure and distribution of electron charge precisely complement those of the ligand - like two pieces of a sophisticated jigsaw puzzle.

When the receptor is occupied by its specific ligand, it alters its 3-dimensional configuration and/or may become bound to a second receptor molecule (dimerize). These changes lead either to alteration (activation or inactivation) of the enzymatic activity of the portion of the receptor inside the cell or to the opening of a pore (hole) in the cell membrane which allows particular ions (like calcium, potassium, or chloride) to leak in or out. In either case, the change in receptor activity influences events within the cell, thus conveying the messenger's signal. Note that, in order for the receptor to function properly, it must change its 3-dimensional configuration or "move" while remaining imbedded in the cell membrane.

 However, cell membranes have been shown to become stiff and viscous with age, as oxidized and otherwise damaged lipids and lipoproteins accumulate within its matrix. Cell membrane fluidity has been shown to increase when fats containing unsaturated fatty acids are substituted for saturated fat in the diet. Moreover, antioxidant vitamins, such as vitamin E, have been reported to improve insulin sensitivity, possibly by reducing the amount of oxidized fat in cell membranes.

A conceptually similar mechanism (signal propagation), also associated with changes in the cell membrane, appears to be, at least partially, responsible for many of the changes observed in cognitive impairment diseases associated with advancing age. The brain of mammals contains high amounts of polyunsaturated fatty acids (PUFA), especially DHA.

There are two kinds of PUFA. One kind, the most common, found in most vegetable oils, is called omega-6; another, found mostly in fish, soybean oil and walnuts, is called omega-3. There is growing evidence that the amount and type (omega-3 vs. omega-6) of PUFA found in the cell membranes of our brain cells is, to a large extent, controlled by our diet.

The importance of omega-3 PUFA in the development and proper function of the brain has been shown in many animals and some human research studies. There is much evidence that omega-3 PUFA is required for proper brain development in infants and children. We believe that omega-3 food intake may also influence rate of loss of some functions with aging.

A large number of older individuals suffer from mild memory loss, known as ARCD (age-related cognitive decline). However, elderly men in Southern Italy, who consume a typical Mediterranean diet, rich in olive oil and fish, appear to be protected.

Also, degenerative diseases of the nervous system, like Parkinson's and Alzheimer's, appear to be associated with decreases in the PUFA content of the cell membrane of the nerve cells. These changes can affect proper cell communication and function (signal propagation).

It is possible to achieve significant changes in the type of fat molecules found in cell membranes after relatively short periods of dietary modifications. We investigated the effects of an omega-3 enriched diet in men and women over 60 years old. We wanted to see if we could improve mental function, hormone levels at rest and/or under stress, and immune function, toward a pattern more like that of younger individuals.

We measured responses to a series of standard endocrine provocative tests and assess the function of immune system cells and measure the fatty acid content of cell membranes from cells obtained from blood samples. A standardized cognitive function test tracked cognitive function parameters.