Free Fatty Acids (FFAs, NEFA)

Free Fatty Acids (FFAs, NEFA) are released from tissues when the body doesn't have enough glucose, and their oxidation blocks the oxidation of glucose even when it becomes available from the breakdown of protein caused by cortisol, which is released during glucose deprivation 1.

The release of FFAs is a response to stress, and is mediated by stress hormones such as adrenaline, cortisol, estrogen, growth hormone, and aldosterone, which inhibit the use of glucose in various tissues in order to spare that glucose for certain areas of the brain and the heart 3.

Excess fat, particularly polyunsaturated fats, can cause insulin resistance by elevating FFAs in the blood 3. This is in contrast to sugar, which is relatively deficient in iron and unsaturated fats, and has a favorable calcium to phosphate ratio and the protective and supportive fructose 4.

FFAs can be formed into triglycerides, converted into ketone bodies, or remain as FFAs in the blood 4. While the formation of ketone bodies has some protective effects, they are produced in a state of metabolic stress.

Unsaturated FFAs can induce conformational changes in human sex hormone-binding protein (SBP), which are reflected in its electrophoretic, immunological, and steroid-binding properties, and may result in lower steroid hormone binding and thus increased free hormone levels 6.

Free fatty acids also stimulate the polymerization of tau and amyloid beta peptides, which are associated with Alzheimer's disease 7. Additionally, unsaturated FFAs were demonstrated to induce beta-amyloid assembly in vitro 7.

Polyunsaturated fatty acids (PUFAs), including omega-3 and omega-6, are potent immunosuppressive agents that can induce T-cell death, and may increase cancer risk 8.