Very little attention has been paid to the more
important qualities of dietary fats and oil. Emphasis has mistakenly
been placed on the ratio of saturated to unsaturated fatty acids,
irrespective of lipid per oxidation and trans-isomerisation. Contrary to
conventional wisdom, unsaturated fats are more toxic than saturated
fats.
The quantity and quality of dietary fat is as important as (if not more important than) the ratio of unsaturated to saturated fatty acid of dietary fats and oils are obtained from fresh, whole, unfractionated and unprocessed food, they will be minimally oxidised and will produce healthy cell membranes with normal Cis-fatty acid configuration. They will enhance a normal balance of prostaglandin.
How much dietary fat and oil can one tolerate without risk? Evidence indicates that between 25 and 35 per cent of dietary calories as fat is safe and nutritious. Attention must be paid to the quality and source of the fat described above. The more oxidised the fats, the less they are tolerated by the human body.
In India, on an average, 35 per cent of dietary calories are consumed edible oil as fat. The quality of unsaturated fatty acid (PUFA) is mostly poor, and there is no consideration for rancidity or trans-summarisation.
When high PUFA oils are consumed, they get oxidised very fast due to unstable bond, producing freer radicals and when they are heated produces lipid peroxides.
If lipid peroxides and free radicals are present, either from dietary source or peroxidation of lipid cell membranes, the synthesis of Prostacyclin is inhibited, while Thromboxane synthesis remains unaffected.
In fact, Prostacyclin is considered as most desirable hormone by the system by virtue of their specific action considered as below:
Prostacyclin
? Reduces the adhesiveness of platelet resulting of free flow of blood cells and plasma;
? Reduces the tendency for fibrin deposition;
? Reduces the Thrombus formation, and
? Reduces the spasm, by relieves the encircling muscle fibre in artery walls
Thromboxane A2
? It is a potent vasoconstrictor;
? It causes the intense spasm in blood vessel walls;
? It stimulates platelet aggregation, and
? It is a potent hypertensive.
(Note: Aspirin irreversibly blocks the formation of Thromboxane A2 in platelet, resulting in inhibitory effects on platelets.)
Points to be remembered
? A recent study has shown that reducing dietary fat from 36 per cent of the total calories to 26 per cent of the total calories can significantly lower blood pressures within eight weeks;
? You must take at least 30 per cent calories from fat;
? Not all saturated fatty acids have the same effect on cholesterol synthesis in the liver.
(a) Lauric acid (C-12), myristic acid (C-14) and palmitic acid (C-16) elevate cholesterol levels, and
(b) Stearic acid (C-18m) carbon saturated lowers cholesterol by 21 per cent more than oleic acid.
? Saturated fatty acids are more stable and do not oxidise, hence they are safer than unsaturated fats, except elevating total cholesterol;
? Mono-unsaturated oils are stable and reduces cholesterol and do not pose a threat to the human body;
? Poly-unsaturated fatty acids (PUFA) can be more hazardous to health as they oxidise faster. They cause arthrosclerosis;
? Poly-unsaturated oil inhibits the thyroid function;
? Poly-unsaturated oil impairs intercellular communications;
? Poly-unsaturated oil has been associated with skin aging;
? Poly-unsaturated oil sensitises the skin to the damage caused by ultra-violet rays;
? Ultra-violet light-induced skin cancer is mediated by unsaturated fats and lipid per oxidation;
? Excessive PUFA oil interferes with learning, brain damage and behaviour;
? PUFA oil suppresses several immune function related to cancer, and
? PUFA is present at high concentration in cancer cells
Experiment 1
Pregnant mice were fed with coconut oil. It was found that the baby mice had normal brains and normal intelligence.
The babies of mice fed with PUFA were found to have smaller brains and inferior intelligence.
Experiment 2
Soya oil was given to nursing mice. The oil incorporated into their brain cells and caused visible structural changes in the cell.
In 1980, shortly after the study, the US Department of Agriculture (USDA) issued a recommendation against the use of soya oil infant formulae.
Human beings evolved consuming a diet that contained about equal amounts of n-3 and n-6 essential fatty acids.
Over the past 100-150 years, there has been an enormous increase in the consumption of n-6 fatty acids due to the increased intake of vegetable oils from corn, sunflower seeds, safflower seeds and soybean.
Today, in Western diets, the ratio of n-6 to n-3 fatty acids ranges from 20-30:1 instead of the traditional range of 1-2:1.
Studies indicate that a high intake of n-6 fatty acids shifts the physiological state to one that is prothrombotic and proaggregatory, characterised by increases in blood viscosity, vasospasm and vasoconstriction and decreases in bleeding time.
n-3 fatty acids, however, have anti-inflammatory, antithrombotic, antiarrhythmic, hypolipidemic and vasodilatory properties. These beneficial effects of n-3 fatty acids have been shown in the secondary prevention of coronary heart disease, hypertension, type-2 diabetes, and in some patients with renal disease, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and chronic obstructive pulmonary disease.
Most of the studies were carried out with fish oils [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]. However, alpha-linolenic acid, found in green leafy vegetables, flaxseed, rapeseed and walnuts, desaturates and elongates in the human body to EPA and DHA, and by itself may have beneficial effects on health and the control of chronic diseases.
Over the past 20 years, many studies and clinical investigations have been carried out on the metabolism of polyunsaturated fatty acids (PUFAs) in general and on n-3 fatty acids in particular.
Today, we know that n-3 fatty acids are essential for normal growth and development and may play an important role in the prevention and treatment of coronary artery disease, hypertension, diabetes, arthritis, other inflammatory and auto-immune disorders and cancer.
Research has been done in animal models, tissue cultures and human beings. The original observational studies have given way to controlled clinical trials. Great progress has taken place in our knowledge of the physiological and molecular mechanisms of the various fatty acids in health and disease.
Specifically, their beneficial effects have been shown in the prevention and management of coronary heart disease, hypertension, type-2 diabetes, renal disease, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and chronic obstructive pulmonary disease.
However, this review focusses on the evolutionary aspects of diet, the biological effects of n-6 and n-3 fatty acids, and the effects of dietary alpha-linolenic acid (ALA) compared with long-chain n-3 derivatives on coronary heart disease and diabetes.
On the basis of estimates from studies in Paleolithic nutrition and modern-day hunter-gatherer populations, it appears that human beings evolved consuming a diet that was much lower in saturated fatty acids than is today’s diet.
Furthermore, the diet contained small and roughly equal amounts of n-6 and n-3 PUFAs (ratio of 1-2:1) and much lower amounts of trans-fatty acids than does today’s diet. The current Western diet is very high in n-6 fatty acids (the ratio of n-6 to n-3 fatty acids is 20-30:1) because of the indiscriminate recommendation to substitute n-6 fatty acids for saturated fats to lower serum cholesterol concentrations.
The intake of n-3 fatty acids is much lower today because of the decrease in fish consumption and the industrial production of animal feeds rich in grains containing n-6 fatty acids, leading to the production of meat rich in n-6 and poor in n-3 fatty acids. The same is true for cultured fish and eggs.
Even cultivated vegetables contain fewer n-3 fatty acids than plants in the wild. To sum up, modern agriculture, with its emphasis on production, has decreased the n-3 fatty acid content in many foods – green leafy vegetables, animal meats, eggs and even fish.
Linoleic acid (LA;18:2n-6) and ALA (18:3n-3) and their long-chain derivatives are important components of animal and plant cell membranes. When humans ingest fish or fish oil, the ingested eicosapentaenoic acid (EPA;20:5n-3) and docosahexaenoic acid (DHA;22:6n-3) partially replace the n-6 fatty acids [especially arachidonic acid (AA;20:4n-6)] in cell membranes, especially those of platelets, erythrocytes, neutrophils, monocytes and liver cells.
As a result, ingestion of EPA and DHA from fish or fish oil leads to:
? Decreased production of prostaglandin E2 metabolits;
? Decreased concentrations of thromboxane A2, a potent platelet aggregator and vasoconstrictor;
? Decreased formation of leukotriene B4, an inducer of inflammation and a powerful inducer of leukocyte chemotaxis and adherence;
? Increased concentrations of thromboxane A3, a weak platelet aggregator and vasoconstrictor;
? Increased concentrations of prostacyclin PGI3, leading to an overall increase in total prostacyclin by increasing PGI3 without decreasing PGI2 (both PGI2 and PGI3 are active vasodilators and inhibitors of platelet aggregation); and
? Increased concentrations of leukotriene B5, a weak inducer of inflammation and chemotactic agent
Because of the increased amounts of n-6 fatty acids in the Western diet, the eicosanoid metabolic products from AA – specifically prostaglandins, thromboxanes, leukotrienes, hydroxy fatty acids and lipoxins – are formed in larger quantities than those formed from n-3 fatty acids, specifically EPA.
The eicosanoids from AA are biologically active in small quantities and if they are formed in large amounts, they contribute to the formation of thrombi and atherosmas; the development of allergic and inflammatory disorders, particularly in susceptible people and cell proliferation.
Thus, a diet rich in n-6 fatty acids shifts the physiologic state to one that is prothrombotic and proaggregatory, with increases in blood viscosity, vasospasm, and vasoconstriction and decreases in bleeding time.
The bleeding time is shorter in groups of patients with hypercholesterolemia, hyperlipoproteinemia, myocardial infarction, other forms of atherosclerotic disease, type-2 diabetes, obesity, and hypertriglyceridemia.
Atherosclerosis is a major complication in type-2 diabetes patients. The bleeding time is longer in women than in men and in younger than in older persons. There are ethnic differences in bleeding time that appear to be related to diet.
The hypolipidemic, antithrombotic, and anti-inflammatory effects of n-3 fatty acids have been studied extensively in animal models, tissue cultures, and cells. As expected earlier studies focussed on mechanisms that involve eicosanoid metabolites.
More recently, however, the effects of fatty acids on gene expression have been investigated and this focus of interest has led to studies at the molecular level.
Previous studies have shown that fatty acids, whether released from membrane phospholipids by cellular phospholipases or made available to the cell from the diet or other aspects of the extracellular environment, are important cell-signalling molecules.
They can act as second messengers or substitute for the classic second messengers of the inositide phospholipids and cyclic AMP signal transduction pathways. They can also act as modulator molecules mediating responses of the cell to extracellular signals. It has been shown that fatty acids rapidly and directly alter the transcription of specific genes.
Several clinical and epidemiologic studies have been conducted to determine the effects of long-chain n-3 PUFAs on various physiologic indexes. Whereas the earlier studies were conducted with large doses of fish or fish oil concentrates, more recent studies have used lower doses.
ALA, the precursor of n-3 fatty acids, can be converted to long-chain n-3 PUFAs, and can therefore be substituted for fish oils. The minimum intake of long-chain n-3 PUFAs needed for beneficial effects depends on the intake of other fatty acids.
Dietary amounts of LA as well as the ratio of LA to ALA appear to be important for the metabolism of ALA to long-chain n-3 PUFAs. Diet researchers showed the while keeping the amount of dietary LA constant, 3.7g ALA appears to have biological effects similar to those of 0.3g long-chain n-3 PUFA with conversion of 11g ALA to 1g long-chain n-3 PUFA.
Thus, a ratio of 4 (15g LA:3.7g ALA) is appropriate for conversion. In human studies, Emken et al showed that the conversion of deuterated ALA to longer-chain metabolites was reduced by 50 per cent when dietary intake of LA was increased from 4.7 per cent to 9.3 per cent of energy as a result of the know competition between n-6 and n-3 fatty acids for desaturation.
Diet researchers further indicated that increasing dietary ALA increases EPA concentrations in plasma phospholipids after both the third and sixth week of intervention. Di-homo gamma linolenic acids (20:3n-6) concentrations were reduced, but AA concentrations were not altered.
The reduction in the ratio of long-chain n-6 PUFAs to long-chain n-3 was greater after the sixth week than after the third week Diet researchers was able to show anti-thrombotic effects by reducing the ratio of n-6 to n-3 fatty acids with ALA-rich vegetable oil.
After ALA supplementation, there was an increase in long-chain n-3 PUFA in plasma and platelet phospholipids and a decrease in platelet aggregation. ALA supplementation did not alter triacylglycerol concentrations. As shown by others, only long-chain n-3 PUFAs have triacylglycerol-lowering effects.
In Australian studies, ventricular fibrillation in rats was reduced with canola oil as much or even more efficiently than with fish oil, an effect attributable to ALA. Further studies should be able to show whether this result is a direct effect of ALA per se or occurs as result of its desaturation and elongation to EPA and DHA.
The diets of Western countries have contained increasingly larger amounts of LA, which has been promoted for its cholesterol-lowering effect. It is now recognised that dietary LA favours oxidative modification of LDL cholesterol, increases platelet response to aggregation, and suppresses the immune system.
In contrast, ALA intake is associated with inhibitory effects on the clotting activity of platelets, on their response to thrombin, and on the regulation of AA metabolism. In clinical studies, ALA contributed to the lowering of blood pressure. In a prospective study, Ascherio et al showed that ALA is inversely related to the risk of coronary heart disease in men.
ALA is not equivalent in its biological effects to the long-chain n-3 fatty acids found in marine oils. EPA and DHA are more rapidly incorporated into plasma and membrane lipids and produce more rapid effects than does ALA.
Relatively large reserves of LA in body fat, as are found in vegans or in the diet of omnivores in Western societies, would tend to slow down the formation of long-chain n-3 fatty acids from ALA.
Therefore, the role of ALA in human nutrition becomes important in terms of long-term dietary intake. One advantage of the consumption of ALA over n-3 fatty acids from fish is that the problem of insufficient vitamin E intake does not exist with high intake of ALA from plant sources.
Most epidemiologic studies and clinical trials using n-3 fatty acids in the form fish or fish oil have been carried out in patients with coronary heart disease.
However, studies have also been carried out on the effects of ALA in normal subjects and in patients with myocardial infarction. The effects of long-chain n-3 fatty acids (EPA and DHA) on factors involved in the pathophysiology of atherosclerosis and inflammation.
The hypolipidemic effects of n-3 fatty acids are similar to those of n-6 fatty acids, provided that they replace saturated fats in the diet. n-3 Fatty acids have the added benefit of consistently lowering serum triacylglycerol concentrations, whereas the n-6 fatty acids do not and may even increase them.
Another important consideration is the finding that during chronic fish-oil feeding postprandial triacylglycerol concentrations decreases.
Furthermore, Nestel reported that comsumption of high amounts of fish oil blunted the expected rise in plasma cholesterol concentrations in humans. These finding are consistent with the low rate of coronary artery disease found in fish-eating populations.
Studies in humans have shown that fish oil reduce the rate of hepatic secretion of VLDL triacylglycerol. In normolipidemic subjects, n-3 fatty acids prevent and rapidly reverse carbohydrate-induced hypertriglyceridemia. There is also evidence from kinetic studies that fish oil increases the fractional catabolic rate of VLDL.
The effects of different doses of fish oil on thrombosis and bleeding time were investigated by Saynor et al. A dose of 1.8g EPA/d did not result in any prolongation in bleeding time, but 4g/d increased bleeding time and decreased platelet count with no adverse effects.
In human studies, there has never been a case of clinical bleeding, even in patients undergoing angioplasty, while the patients were taking fish oil supplements.
(The author is diet researcher and nutritional bio-chemist. He can be contacted at alphacardio@yahoo.com)
The quantity and quality of dietary fat is as important as (if not more important than) the ratio of unsaturated to saturated fatty acid of dietary fats and oils are obtained from fresh, whole, unfractionated and unprocessed food, they will be minimally oxidised and will produce healthy cell membranes with normal Cis-fatty acid configuration. They will enhance a normal balance of prostaglandin.
How much dietary fat and oil can one tolerate without risk? Evidence indicates that between 25 and 35 per cent of dietary calories as fat is safe and nutritious. Attention must be paid to the quality and source of the fat described above. The more oxidised the fats, the less they are tolerated by the human body.
In India, on an average, 35 per cent of dietary calories are consumed edible oil as fat. The quality of unsaturated fatty acid (PUFA) is mostly poor, and there is no consideration for rancidity or trans-summarisation.
When high PUFA oils are consumed, they get oxidised very fast due to unstable bond, producing freer radicals and when they are heated produces lipid peroxides.
If lipid peroxides and free radicals are present, either from dietary source or peroxidation of lipid cell membranes, the synthesis of Prostacyclin is inhibited, while Thromboxane synthesis remains unaffected.
In fact, Prostacyclin is considered as most desirable hormone by the system by virtue of their specific action considered as below:
Prostacyclin
? Reduces the adhesiveness of platelet resulting of free flow of blood cells and plasma;
? Reduces the tendency for fibrin deposition;
? Reduces the Thrombus formation, and
? Reduces the spasm, by relieves the encircling muscle fibre in artery walls
Thromboxane A2
? It is a potent vasoconstrictor;
? It causes the intense spasm in blood vessel walls;
? It stimulates platelet aggregation, and
? It is a potent hypertensive.
(Note: Aspirin irreversibly blocks the formation of Thromboxane A2 in platelet, resulting in inhibitory effects on platelets.)
Points to be remembered
? A recent study has shown that reducing dietary fat from 36 per cent of the total calories to 26 per cent of the total calories can significantly lower blood pressures within eight weeks;
? You must take at least 30 per cent calories from fat;
? Not all saturated fatty acids have the same effect on cholesterol synthesis in the liver.
(a) Lauric acid (C-12), myristic acid (C-14) and palmitic acid (C-16) elevate cholesterol levels, and
(b) Stearic acid (C-18m) carbon saturated lowers cholesterol by 21 per cent more than oleic acid.
? Saturated fatty acids are more stable and do not oxidise, hence they are safer than unsaturated fats, except elevating total cholesterol;
? Mono-unsaturated oils are stable and reduces cholesterol and do not pose a threat to the human body;
? Poly-unsaturated fatty acids (PUFA) can be more hazardous to health as they oxidise faster. They cause arthrosclerosis;
? Poly-unsaturated oil inhibits the thyroid function;
? Poly-unsaturated oil impairs intercellular communications;
? Poly-unsaturated oil has been associated with skin aging;
? Poly-unsaturated oil sensitises the skin to the damage caused by ultra-violet rays;
? Ultra-violet light-induced skin cancer is mediated by unsaturated fats and lipid per oxidation;
? Excessive PUFA oil interferes with learning, brain damage and behaviour;
? PUFA oil suppresses several immune function related to cancer, and
? PUFA is present at high concentration in cancer cells
Experiment 1
Pregnant mice were fed with coconut oil. It was found that the baby mice had normal brains and normal intelligence.
The babies of mice fed with PUFA were found to have smaller brains and inferior intelligence.
Experiment 2
Soya oil was given to nursing mice. The oil incorporated into their brain cells and caused visible structural changes in the cell.
In 1980, shortly after the study, the US Department of Agriculture (USDA) issued a recommendation against the use of soya oil infant formulae.
Human beings evolved consuming a diet that contained about equal amounts of n-3 and n-6 essential fatty acids.
Over the past 100-150 years, there has been an enormous increase in the consumption of n-6 fatty acids due to the increased intake of vegetable oils from corn, sunflower seeds, safflower seeds and soybean.
Today, in Western diets, the ratio of n-6 to n-3 fatty acids ranges from 20-30:1 instead of the traditional range of 1-2:1.
Studies indicate that a high intake of n-6 fatty acids shifts the physiological state to one that is prothrombotic and proaggregatory, characterised by increases in blood viscosity, vasospasm and vasoconstriction and decreases in bleeding time.
n-3 fatty acids, however, have anti-inflammatory, antithrombotic, antiarrhythmic, hypolipidemic and vasodilatory properties. These beneficial effects of n-3 fatty acids have been shown in the secondary prevention of coronary heart disease, hypertension, type-2 diabetes, and in some patients with renal disease, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and chronic obstructive pulmonary disease.
Most of the studies were carried out with fish oils [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]. However, alpha-linolenic acid, found in green leafy vegetables, flaxseed, rapeseed and walnuts, desaturates and elongates in the human body to EPA and DHA, and by itself may have beneficial effects on health and the control of chronic diseases.
Over the past 20 years, many studies and clinical investigations have been carried out on the metabolism of polyunsaturated fatty acids (PUFAs) in general and on n-3 fatty acids in particular.
Today, we know that n-3 fatty acids are essential for normal growth and development and may play an important role in the prevention and treatment of coronary artery disease, hypertension, diabetes, arthritis, other inflammatory and auto-immune disorders and cancer.
Research has been done in animal models, tissue cultures and human beings. The original observational studies have given way to controlled clinical trials. Great progress has taken place in our knowledge of the physiological and molecular mechanisms of the various fatty acids in health and disease.
Specifically, their beneficial effects have been shown in the prevention and management of coronary heart disease, hypertension, type-2 diabetes, renal disease, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and chronic obstructive pulmonary disease.
However, this review focusses on the evolutionary aspects of diet, the biological effects of n-6 and n-3 fatty acids, and the effects of dietary alpha-linolenic acid (ALA) compared with long-chain n-3 derivatives on coronary heart disease and diabetes.
On the basis of estimates from studies in Paleolithic nutrition and modern-day hunter-gatherer populations, it appears that human beings evolved consuming a diet that was much lower in saturated fatty acids than is today’s diet.
Furthermore, the diet contained small and roughly equal amounts of n-6 and n-3 PUFAs (ratio of 1-2:1) and much lower amounts of trans-fatty acids than does today’s diet. The current Western diet is very high in n-6 fatty acids (the ratio of n-6 to n-3 fatty acids is 20-30:1) because of the indiscriminate recommendation to substitute n-6 fatty acids for saturated fats to lower serum cholesterol concentrations.
The intake of n-3 fatty acids is much lower today because of the decrease in fish consumption and the industrial production of animal feeds rich in grains containing n-6 fatty acids, leading to the production of meat rich in n-6 and poor in n-3 fatty acids. The same is true for cultured fish and eggs.
Even cultivated vegetables contain fewer n-3 fatty acids than plants in the wild. To sum up, modern agriculture, with its emphasis on production, has decreased the n-3 fatty acid content in many foods – green leafy vegetables, animal meats, eggs and even fish.
Linoleic acid (LA;18:2n-6) and ALA (18:3n-3) and their long-chain derivatives are important components of animal and plant cell membranes. When humans ingest fish or fish oil, the ingested eicosapentaenoic acid (EPA;20:5n-3) and docosahexaenoic acid (DHA;22:6n-3) partially replace the n-6 fatty acids [especially arachidonic acid (AA;20:4n-6)] in cell membranes, especially those of platelets, erythrocytes, neutrophils, monocytes and liver cells.
As a result, ingestion of EPA and DHA from fish or fish oil leads to:
? Decreased production of prostaglandin E2 metabolits;
? Decreased concentrations of thromboxane A2, a potent platelet aggregator and vasoconstrictor;
? Decreased formation of leukotriene B4, an inducer of inflammation and a powerful inducer of leukocyte chemotaxis and adherence;
? Increased concentrations of thromboxane A3, a weak platelet aggregator and vasoconstrictor;
? Increased concentrations of prostacyclin PGI3, leading to an overall increase in total prostacyclin by increasing PGI3 without decreasing PGI2 (both PGI2 and PGI3 are active vasodilators and inhibitors of platelet aggregation); and
? Increased concentrations of leukotriene B5, a weak inducer of inflammation and chemotactic agent
Because of the increased amounts of n-6 fatty acids in the Western diet, the eicosanoid metabolic products from AA – specifically prostaglandins, thromboxanes, leukotrienes, hydroxy fatty acids and lipoxins – are formed in larger quantities than those formed from n-3 fatty acids, specifically EPA.
The eicosanoids from AA are biologically active in small quantities and if they are formed in large amounts, they contribute to the formation of thrombi and atherosmas; the development of allergic and inflammatory disorders, particularly in susceptible people and cell proliferation.
Thus, a diet rich in n-6 fatty acids shifts the physiologic state to one that is prothrombotic and proaggregatory, with increases in blood viscosity, vasospasm, and vasoconstriction and decreases in bleeding time.
The bleeding time is shorter in groups of patients with hypercholesterolemia, hyperlipoproteinemia, myocardial infarction, other forms of atherosclerotic disease, type-2 diabetes, obesity, and hypertriglyceridemia.
Atherosclerosis is a major complication in type-2 diabetes patients. The bleeding time is longer in women than in men and in younger than in older persons. There are ethnic differences in bleeding time that appear to be related to diet.
The hypolipidemic, antithrombotic, and anti-inflammatory effects of n-3 fatty acids have been studied extensively in animal models, tissue cultures, and cells. As expected earlier studies focussed on mechanisms that involve eicosanoid metabolites.
More recently, however, the effects of fatty acids on gene expression have been investigated and this focus of interest has led to studies at the molecular level.
Previous studies have shown that fatty acids, whether released from membrane phospholipids by cellular phospholipases or made available to the cell from the diet or other aspects of the extracellular environment, are important cell-signalling molecules.
They can act as second messengers or substitute for the classic second messengers of the inositide phospholipids and cyclic AMP signal transduction pathways. They can also act as modulator molecules mediating responses of the cell to extracellular signals. It has been shown that fatty acids rapidly and directly alter the transcription of specific genes.
Several clinical and epidemiologic studies have been conducted to determine the effects of long-chain n-3 PUFAs on various physiologic indexes. Whereas the earlier studies were conducted with large doses of fish or fish oil concentrates, more recent studies have used lower doses.
ALA, the precursor of n-3 fatty acids, can be converted to long-chain n-3 PUFAs, and can therefore be substituted for fish oils. The minimum intake of long-chain n-3 PUFAs needed for beneficial effects depends on the intake of other fatty acids.
Dietary amounts of LA as well as the ratio of LA to ALA appear to be important for the metabolism of ALA to long-chain n-3 PUFAs. Diet researchers showed the while keeping the amount of dietary LA constant, 3.7g ALA appears to have biological effects similar to those of 0.3g long-chain n-3 PUFA with conversion of 11g ALA to 1g long-chain n-3 PUFA.
Thus, a ratio of 4 (15g LA:3.7g ALA) is appropriate for conversion. In human studies, Emken et al showed that the conversion of deuterated ALA to longer-chain metabolites was reduced by 50 per cent when dietary intake of LA was increased from 4.7 per cent to 9.3 per cent of energy as a result of the know competition between n-6 and n-3 fatty acids for desaturation.
Diet researchers further indicated that increasing dietary ALA increases EPA concentrations in plasma phospholipids after both the third and sixth week of intervention. Di-homo gamma linolenic acids (20:3n-6) concentrations were reduced, but AA concentrations were not altered.
The reduction in the ratio of long-chain n-6 PUFAs to long-chain n-3 was greater after the sixth week than after the third week Diet researchers was able to show anti-thrombotic effects by reducing the ratio of n-6 to n-3 fatty acids with ALA-rich vegetable oil.
After ALA supplementation, there was an increase in long-chain n-3 PUFA in plasma and platelet phospholipids and a decrease in platelet aggregation. ALA supplementation did not alter triacylglycerol concentrations. As shown by others, only long-chain n-3 PUFAs have triacylglycerol-lowering effects.
In Australian studies, ventricular fibrillation in rats was reduced with canola oil as much or even more efficiently than with fish oil, an effect attributable to ALA. Further studies should be able to show whether this result is a direct effect of ALA per se or occurs as result of its desaturation and elongation to EPA and DHA.
The diets of Western countries have contained increasingly larger amounts of LA, which has been promoted for its cholesterol-lowering effect. It is now recognised that dietary LA favours oxidative modification of LDL cholesterol, increases platelet response to aggregation, and suppresses the immune system.
In contrast, ALA intake is associated with inhibitory effects on the clotting activity of platelets, on their response to thrombin, and on the regulation of AA metabolism. In clinical studies, ALA contributed to the lowering of blood pressure. In a prospective study, Ascherio et al showed that ALA is inversely related to the risk of coronary heart disease in men.
ALA is not equivalent in its biological effects to the long-chain n-3 fatty acids found in marine oils. EPA and DHA are more rapidly incorporated into plasma and membrane lipids and produce more rapid effects than does ALA.
Relatively large reserves of LA in body fat, as are found in vegans or in the diet of omnivores in Western societies, would tend to slow down the formation of long-chain n-3 fatty acids from ALA.
Therefore, the role of ALA in human nutrition becomes important in terms of long-term dietary intake. One advantage of the consumption of ALA over n-3 fatty acids from fish is that the problem of insufficient vitamin E intake does not exist with high intake of ALA from plant sources.
Most epidemiologic studies and clinical trials using n-3 fatty acids in the form fish or fish oil have been carried out in patients with coronary heart disease.
However, studies have also been carried out on the effects of ALA in normal subjects and in patients with myocardial infarction. The effects of long-chain n-3 fatty acids (EPA and DHA) on factors involved in the pathophysiology of atherosclerosis and inflammation.
The hypolipidemic effects of n-3 fatty acids are similar to those of n-6 fatty acids, provided that they replace saturated fats in the diet. n-3 Fatty acids have the added benefit of consistently lowering serum triacylglycerol concentrations, whereas the n-6 fatty acids do not and may even increase them.
Another important consideration is the finding that during chronic fish-oil feeding postprandial triacylglycerol concentrations decreases.
Furthermore, Nestel reported that comsumption of high amounts of fish oil blunted the expected rise in plasma cholesterol concentrations in humans. These finding are consistent with the low rate of coronary artery disease found in fish-eating populations.
Studies in humans have shown that fish oil reduce the rate of hepatic secretion of VLDL triacylglycerol. In normolipidemic subjects, n-3 fatty acids prevent and rapidly reverse carbohydrate-induced hypertriglyceridemia. There is also evidence from kinetic studies that fish oil increases the fractional catabolic rate of VLDL.
The effects of different doses of fish oil on thrombosis and bleeding time were investigated by Saynor et al. A dose of 1.8g EPA/d did not result in any prolongation in bleeding time, but 4g/d increased bleeding time and decreased platelet count with no adverse effects.
In human studies, there has never been a case of clinical bleeding, even in patients undergoing angioplasty, while the patients were taking fish oil supplements.
(The author is diet researcher and nutritional bio-chemist. He can be contacted at alphacardio@yahoo.com)
