Fats for LifeJuly 2001
By Karin Granstrom Jordan, M.D.
Stress and behavior
Repeated exposure to psychosocial stressors as well as exaggerated reactivity to stress have been implicated as factors in the development of hypertension and heart disease. In addition, chronically elevated levels of stress-related hormones (catecholamines and glucocorticoids) are known to inhibit the activity of D6D, the enzyme needed for metabolism of EFAs.
Several early studies on rats found that dietary omega-6 and omega-3 fatty acids reduced the cardiovascular reaction to stress (Mills et al., 1985, 1986). Hence it is not surprising that both GLA and DHA have been found to reduce blood pressure and heart rate responses to psychosocial stress in humans.
Mills extended his findings to humans in a four-week study on 30 male university students (1989). Three different treatment groups were given either borage oil (1.3g/d), fish oil (1.6 g/d) or olive oil (as placebo). Borage oil significantly reduced stress-induced systolic blood pressure and heart rate after four weeks of supplementation, whereas olive oil and fish oil were without effect. Task performance was also significantly improved in the borage oil group, while un-changed by olive oil and fish oil, in a test that required a high level of attention and was designed to measure the cardiovscular response to psychological stress.
These results were similar to findings in the earlier animal studies and suggest that borage oil supplementation is effective in reducing cardiovascular reactions to stressors of all kinds, of both short and long-term, psychological and physical nature.
As a follow-up to earlier findings that DHA intake prevents aggression from increasing at times of mental stress (Hamazaki et al., 1996) Sawazaki et al. (1999) conducted an excellent double-blind study to test the effect of DHA intake on the level of stress hormones (epinephrine and norepinephrine). Fourteen medical students were studied over a stressful nine-week period when they underwent over 20 final exams. The participants in the DHA group were given 1.5 g DHA/day, while the control group members were given a mix of plant oils, all in capsules taken with meals.
The norepinephrine levels were high in both groups at the beginning of the study, since the students had already been under stress for some time, preparing for the exams. At the end of the test period the DHA group showed significantly reduced (-31%) norepinephrine levels, which is believed to be protective and beneficial for the cardiovascular system. In the control group the norepinephrine levels were still high. Epinephrine and cortisol showed no significant changes in either group. (Elevated norepinephrine levels are associated with chronic stress, while epine-phrine increases in situations of acute “survival” stress).
Similar findings of reduced norepinephrine levels related to EFA intake have been reported by other authors (Singer et al., 1990; Christensen et al., 1994). In Singer’s study on 47 hypertensive individuals, norepinephrine levels were reduced 80% after treatment with omega-3 fatty acids compared to the control groups. Christensen’s study showed that norepinephrine levels of men who died from cardiovascular disease were significantly higher than those of survivors.
Interestingly, the students in Awazaki’s study were under considerable stress even long before the testing began, and the baseline levels of norepinephrine were already high at the start. This means that DHA was able to modulate catecholamine meta-bolism even after the appearance of stress. This is a noteworthy point when applying these results to daily life, as we usually do not try to counteract stress until after it starts.
Insulin resistance is a common phenomenon in aging and in simple overweight. It is a primary factor in the so called metabolic syndrome X and is strongly linked to the development of a cluster of common age-related disorders including type 2 diabetes, obesity, hypertension, hyperlipidemia and heart disease. Insulin resistance is found in approximately 25% of apparently healthy humans.
Insulin resistance means that cells are desensitized to insulin signaling that normally leads to glucose uptake. The body tries to compensate for higher levels of circulating glucose by increasing insulin production. When this temporary compensatory mechanism fails, the glucose levels stay elevated, leading to diabetes and other degenerative complications.
Research has now shown a strong connection between the intake of essential fatty acids, in particular GLA and DHA, and improved insulin sensitivity (reduced insulin resistance).
importance for the development and
maintenance of brain function, both in
young and old individuals.
Both human and animal studies show that a dietary intake of EFAs both increases the unsaturated fatty acids in membrane phospholipids and makes the individual more insulin sensitive (Storlien et al., 1986, 1987; Borkman et al., 1993; Vessby et al., 1994; Pan et al., 1995; Storlien et al., 1996).
Until recently, however, scientists did not understand the deeper mechanisms behind the influence of EFAs on insulin resistance. The discovery of a fundamental mechanism for the regulation of fat metabolism in the body has shed light on the effect of EFAs: the nuclear receptors and transcription factors called peroxisome proliferator-activated receptors or PPARs (See side bar on previous page).
Recently developed drugs, called glitazones or thiazolidinediones, that bind to and activate PPAR, increase insulin sensitivity. We now know that GLA and DHA, as well as certain other EFAs work in the same way, binding to and activating PPAR.
Brain development and learning
In the last decade DHA has been discovered to be of major importance for the development and maintenance of brain function, both in young and old individuals. As the major structural and functional EFA of the central nervous system, including the retina of the eye (Connor et al., 1992), it constitutes as much as 30% to 50% of the total fatty acid content of the human brain and is essential for optimal neurological function. Part of the reason for this unique function is the role of DHA in the synthesis of phospholipids in nerve cell membranes.
Nothing can be more important than an adequate supply of DHA at the beginning of life, since it is essential for the growth and functional development of the brain in infants. DHA deficiencies in infancy have been associated with visual impairment and the later development of disorders including attention deficit hyperactivity disorder (ADHD), learning disabilities and aggressive behavior. DHA is also required for the maintenance of normal brain function in adults, for learning and for memory, and low levels have been shown to be a risk factor for Alzheimer’s disease (Horrocks et al., 1999).
Many experimental studies on mice and rats have been conducted to clarify the effects of DHA on learning and memory. These studies clearly indicate that DHA deficiency is associated with a loss of discriminative learning ability (Greiner et al., 1999), while omega-3 enriched diets increase learning ability in elderly animals.
The Japanese research team Lim and Suzuki demonstrated superior maze-learning ability in old mice fed a DHA supplemented diet. After four months on the diet the mice made significantly fewer mistakes and spent less time in the maze than the control group. They even performed better than the young rats on the control diet (Lim & Suzuki, 2000). When the re-searchers studied the relationship between the time of DHA intake and maze behavior, they found that an improved maze-learning ability was evident at one month after the feeding started, whereas increased DHA levels in the brain were apparent as early as two weeks. These results suggest that improvement in learning ability may take some time after the incorporation of DHA into the brain (Lim & Suzuki, 2001).
As we have seen, aging is often connected to a decreased meta-bolism of EFAs. Changes in the fatty aid composition of brain lipids during aging appear to be correlated with a deterioration of the central nervous system. Knowing that DHA constitutes a major portion of the fatty acids in the brain, it may not be surprising that low DHA levels are shown to be a significant risk factor for the development of Alzheimer’s disease.
In a recent study tracking DHA levels in 1188 elderly American subjects for 10 years, Alzheimer’s disease was 67% more likely to develop in individuals with DHA levels in the lower half of the distribution (Kyle et al., 1999).
Brain cholinergic systems are generally thought to be critical for memory function. Dysfunction of the central cholinergic system has been seen both in patients with vascular dementia and with senile dementia of Alzheimer’s type. In a study on stroke-prone spontaneously hypertensive rats Minami et al. (1997) demonstrated that DHA increased choline and acetylcholine levels in the brain, while improving passive avoidance performance.
Interesting results from a Japanese clinical trial on DHA and dementia provide encouragement for further research. This pilot study involved 20 elderly people (average 83 years) with moderately severe dementia from thrombotic cerebrovascular disorder (stroke) (Terano et al., 1999). The participants all lived in the same home for the elderly and ate the same food. They were divided into two groups according to age and baseline scores on psychometric tests. The individuals in the treatment group received 720 mg of DHA daily for one year. Significant improvement in the dementia scores was noticeable after three to six months of DHA supplementation. The control group showed no improvement.
With all these benefits of GLA and DHA in mind it is important to remember that too much of a good thing is not always good. Balance is the key, in this case between omega-6 and omega-3 fatty acids. The easiest and safest way to accomplish this balance is by taking a high quality combination supplement (ideally in the 2:1 range), while reducing dietary intake of saturated and hydrogenated fats.
Through the simple and safe procedure of supplementing our diet with a balanced combination of GLA and DHA it seems evident from current research that we have the chance to prevent a significant portion of the age-related degenerative diseases that plague our society today. It will ease our bodies’ response to stress and may even help us to escape dementia.