Fats for LifeJuly 2001
By Karin Granstrom Jordan, M.D.
Recently it has been discovered that elevated levels of the mineralocorticoid hormone aldosterone plays a much larger role in hypertension and cardiac disease than previously believed. Aldosterone-reducing drugs are used in the treatment of hypertension and have recently been discovered to be effective also for treatment of heart failure (Weber, 1999).
In addition to many other mechanisms of action, both GLA and DHA have now been found to inhibit aldosterone production, which may be a discovery of great importance in the prevention of cardiovascular disease.
One of the key mechanisms in the regulation of blood pressure is the renin-angiotensin-aldosterone system. Renin is released from the kidneys in response to low blood pressure and stimulates the production of aldosterone via several intermediate steps, including angi-otensin I and II. Aldosterone controls sodium and water uptake in the kidneys, and elevated levels increase the blood pressure.
Not all cases of hypertension, however, are triggered through the renin-angiotensin system. So-called primary aldosteronism has traditionally been regarded as a rare cause of hypertension (1%) but has recently been discovered to be more frequent than earlier believed (10% to 15% of patients with essential hypertension) (Fardella et al., 1999). This condition is characterized by excess production of aldosterone in the adrenal gland, without involvement of the renin-angiotensin-aldosterone system. Characteristic features of primary aldosteronism are high aldosterone levels, low renin levels and a high aldosterone/renin ratio.
Since elevated aldosterone levels have been found to play such a major role in hypertension, a research team under Marguerite Engler investigated the relationship between GLA, DHA and aldosterone in animals. In several previous experimental studies Engler et al. had demonstrated that borage oil and DHA have blood pressure lowering effects in hypertensive, normotensive, old and young rats (Engler et al., 1992, 1993). When the scientists studied the effects of GLA and DHA on the renin-angiotensin-aldosterone system in rats, genetically programmed for hypertension (Engler et al., 1998 and 1999), it became clear that both these EFAs affect the renin-angiotensin-aldosterone system. Although in slightly different ways, both GLA and DHA decreased the production of aldosterone. In the GLA study the aldosterone/renin ratio was significantly lower in the borage oil group than in the control group given sesame oil. In the DHA study aldosterone was significantly lowered (33%) compared to the control group fed a diet containing corn/soybean oil. A remarkable reduction of the systolic blood pressure was also seen in both studies. In the borage oil group the decrease was 12 mmHg after three weeks, and in the DHA study the blood pressure was 34 mmHg lower on an average after six weeks.
The observations in these studies suggested that borage oil (GLA) inhibits the adrenal responsiveness to angiotensin II through diminished angiotensin receptor activity in aldosterone producing cells. Decreased aldosterone levels stimulate renin secretion and the net effect is a desirable reduction in the aldosterone/renin ratio. DHA on the other hand, appears to affect the aldosterone production without involving angiotensin receptors.
Kimura et al. (1995) found that DHA supplementation could to a large extent prevent an increase in blood pressure in rats genetically programmed to develop hypertension and stroke (spontaneously hypertensive rats). While the average blood pressure in the control group of young rats on “normal” diet increased form 120.2 to 202.9 mmHg during the test period, blood pressure in the DHA supplemented group only increased to 149.8 mmHg. Serum creatinine levels and blood urea nitrogen were significantly lower in the DHA group, which indicates beneficial changes in renal function.
These experimental blood pressure lowering effects on rats have been confirmed in clinical trials on humans. Mori et al. (1999) conducted an interesting, double-blind, placebo-controlled trial with 59 overweight, hyperlipidemic men to compare the effects of purified EPA, DHA and olive oil supplementation (4g/d in capsules). Only DHA had significant blood pressure and heart rate lowering effects. Systolic and diastolic blood pressure fell on average 5.8 and 3.3 mmHg respectively, and daytime heart rate fell 3.7 bpm. These results also show that DHA, rather than EPA, is the principal omega-3 fatty acid in fish and fish oils responsible for their beneficial effects on the cardiovascular system.
The beneficial effects of the omega-3 fatty acids EPA and DHA had previously been attributed mainly to EPA because of its predominance in fish oil. However, it has recently become clear that DHA is the more important of the two. For example, in comparison to EPA, DHA has consistently proven to be more effective in lowering plasma triglycerides, increasing HDL cholesterol levels and lowering blood pressure and heart rate, while also being unique in its effect on the central nervous system.
In another randomized clinical trial a combination of highly purified DHA and EPA significantly reduced blood pressure in mildly hypertensive men (Prisco et al, 1998). Daily supplementation with 1.4 g DHA and 2.04 g EPA resulted in a decrease in both systolic (6 mmHg) and diastolic (5 mmHg) blood pressure after two months. No further effect was observed at four months and there was a return to baseline levels after two months without supplementation.
Serum lipids (Cholesterol and triglycerides)
GLA and DHA have repeatedly shown a remarkable effect on the reduction of cholesterol and triglyceride levels in both animal and human studies.
In a clinical trial involving 12 hyperlipidemic men GLA supplementation of 240 mg/day was given for four months. The results demonstrated a significant average reduction of triglyceride levels (48%), most of which was achieved as early as four weeks after the start. Total cholesterol and LDL-cholesterol levels were significantly decreased, whereas the good HDL cholesterol was significantly increased (22%). (Guivernau et al., 1994).
While most studies of omega-3 supplementation have been done on men, an interesting study on the effects of omega-3 fatty acids on serum lipids in post-menopausal women was recently published (Stark et al., 2000). In this placebo-controlled, double-blind trial, 36 women received either omega-3 fatty acids (2.4 g/d EPA and 1.6 g/d DHA) or placebo oil. After 28 days of supplementation there was a marked reduction in serum triglycerides (26%) and a 28% lower ratio of triglycerides to HDL-cholesterol. Women with and without hormone replacement had the same results.
The long-term prevention of atherosclerosis does not, as we now know, depend entirely on lowering cholesterol and triglyceride levels, but rather on increasing the good HDL-cholesterol. Reduced incidence of cardiovascular disease has been observed in the presence of high HDL levels. Specific subfractions of HDL appear to be involved in this process.
A study on 350 men and women with normal blood pressure demonstrated an increase of HDL2, a particularly beneficial subgroup of HDL-cholesterol, particularly in women, when given omega-3 fatty acids for six months (Sacks et al., 1994).
The effects of GLA on subfractions of HDL were studied in rabbits due to their similarity of plasma lipoprotein to humans (Fragoso et al., 1992). After four weeks of GLA supplementation there were no changes in the total cholesterol and triglyceride levels, but large changes in the distribution of HDL subfractions. A relative increase in the proportion of HDL2b and HDL3c was observed, an alteration that returned to basal levels 12 weeks after GLA withdrawal. This is especially noteworthy since the HDL2b subfraction is increased in centenarians as compared to both ‘middle-aged’ and ‘elderly’ subjects according to a study on long-lived individuals conducted by Barbagallo et al. (1998). In the same study HDL2b was also found to be inversely correlated with coronary heart disease and therefore likely to favor healthy aging.