Depression and psychological changes associated with dieting and weight cycling may also be related to alterations in EFA metabolism. Severe food restriction and very low-fat diets can induce changes in n-3 and n-6 fatty acid balance. Given the influence that these fatty acids can have on brain chemistry, extremely low-fat diets that alter EFA intake may have negative cognitive consequences.

Based on empirical findings, Yehuda et al suggest, among other things, that the critical factor in FA action and efficacy is not the absolute levels. Rather, it is the ratio between various groups of FAs acting as mediators of brain biochemistry and cognitive functions.

In an animal study using mice, Wainwright et al further demonstrated this idea. They found growth retardation in the offspring of female mice fed a diet with abnormal n-6 to n-3 ratio (0.32), but high DHA content compared with normal ratios (4.0).

In an animal study using mice, Wainwright et al further demonstrated this idea. They found growth retardation in the offspring of female mice fed a diet with abnormal n-6 to n-3 ratio (0.32), but high DHA content compared with normal ratios (4.0).

Research has also uncovered the following: ƒ Uauy et al, while demonstrating the structural and functional role of EFAs in early life, determined that the most significant effects relate to neural development.

Youdim et al showed that declining levels of PUFAs are associated with cognitive impairment and neurodegenerative disorders, such as Parkinson's and Alzheimer's.

Fenton et al showed that deficient uptake or excessive breakdown of membrane phospholipids may be associated with schizophrenia.

Many other studies further support the role of balanced PUFAs and their role in behavior, cognitive function and neurological development.

Osteoporosis

When one thinks about EFAs, the topic of osteoporosis is not usually is not the first thing that comes to mind. However, the literature has identified a relationship between EFAs and bone metabolism, and that relationship has recently been gaining increased attention.

Soon after Burr and Burr identified EFAs, Borland and Jackson demonstrated that EFA-deficient animals developed calcified kidneys, due to a shift of calcium out of the bones. Unfortunately, this observation was not followed up with further research for approximately 20 years. It was then reported that EFA deficiency in animals can result in a loss of normal collagen and cartilage synthesis, as well as bone demineralization.

The streptozotocin-diabetic rat experiences significant hypercalcemia and has been used as a model to study the effect of EFAs on calcium metabolism. It is now understood that metabolites of both n-6 and n-3 fatty acids can reduce urinary calcium excretion.

Kruger and Horrobin, who postulated this, also noted that EFA-deficient animals developed severe osteoporosis, coupled with increased renal and arterial calcification. The authors point out that this calcification may be considerably more dangerous than the osteoporosis itself. Balanced n-6 and n-3 supplementation was noted to not only decrease urinary calcium excretion, but also to reduce ectopic calcifications and increase calcium deposition in bone. It was also observed to increase calcium absorption from the gut.

The mechanism by which EFAs alter calcium excretion needs to be further clarified. However, many researchers have shown that PGE2 increases urinary calcium excretion, and inhibition of PGE2 levels can reduce calcium losses. Since PGE2 production results from AA metabolism, a favorable balance of n-3 and n-6 fatty acids should positively effect calcium excretion.

Buck et al reported such a finding, demonstrating that a combination of n-6 and n-3 fatty acids significantly decreased urinary calcium. As previously mentioned, EFAs have also been shown to affect calcium absorption from the gastrointestinal tract, as there is a close relationship between calcium transport, EFAs, and vitamin D.

Van Dokkum et al demonstrated that EFA supplementation in humans reduced fecal calcium losses and stimulated calcium absorption from the gut. Using radioisotopes, Buck et al reported that supplementation with either fish oil, evening primrose oil, or a combination of the two, significant increased calcium absorption. It has been hypothesized that changes in membrane composition, due to EFA supplementation, may alter ion pump activity or ion channel function. That, in turn, enhances the intestinal response to vitamin D.

EFAs are also able to affect bone metabolism. While beyond the scope of this discussion, it is well known that prostagladins influence bone metabolism. Given the ability of EFAs to influence prostaglandin formation, EFAs may have potent bone-stimulating actions. Watkins et al demonstrated in animals that EPA supplementation can stimulate bone formation in association with reduced amounts of PGE2.

Van Papendorp et al supplemented osteoporotic women with evening primrose oil, fish oil, a combination of the two, or olive oil, for 16 weeks. Alkaline phosphatase was significantly decreased, while osteocalcin levels increased in the group receiving fish oil, and in the group receiving a combination of fish oil and evening primrose oil.