I was recently spurred to review the polyunsaturated fatty acid story, also known as the omega stuff, by an online acquaintance, David Brown, who is a maven on this subject.
One aspect of lipid science that needs further elucidation is the toxicity problem. All polyunsaturated fatty acids are biologically active molecules as noted in this comment by Norwegian animal science researchers.
"Because arachidonic acid (AA) competes with EPA and DHA as well as with LA, ALA and oleic acid for incorporation in membrane lipids at the same positions, all these fatty acids are important for controlling the AA concentration in membrane lipids, which in turn determines how much AA can be liberated and become available for prostaglandin biosynthesis following phospholipase activation. Thus, the best strategy for dampening prostanoid overproduction in disease situations would be to reduce the intake of AA, or reduce the intake of AA at the same time as the total intake of competing fatty acids (including oleic acid) is enhanced, rather than enhancing intakes of EPA and DHA only. Enhancement of membrane concentrations of EPA and DHA will not be as efficient as a similar decrease in the AA concentration for avoiding prostanoid overproduction."
"Combining reduction of the intake of AA with enhancement of the intake of oleic acid will, moreover, also be a better strategy for reducing the total extent of in vivo lipid peroxidation, rather than adding more EPA (with 5 double bonds) and DHA (with 6 double bonds) to a diet already over-abundant in arachidonic acid and linoleic acid. A reduction of the dietary ratio of total polyunsaturated fatty acids to oleic acid will not only make plasma lipoproteins less vulnerable to oxidation, but must also be expected to lead to reduction of the rate of formation of mutagenic aldehydes that arise as secondary products of lipid peroxidation, such as malondialdehyde, crotonaldehyde, acrolein and 4-hydroxynonenal. High rates of production of these mutagenic aldehydes must be expected simultaneously to lead to enhancement of the risk of various forms of cancer, and enhancement of the rate of mitochondrial DNA aging, which could lead to earlier onset of various age-associated degenerative diseases perhaps including type 2 diabetes. The degree of fatty acid unsaturation of mitochondrial membrane lipids has been found to be one of those biochemical parameters that are most strongly correlated with longevity, when different species of mammals and birds are compared, with a low degree of fatty unsaturation being correlated with less lipid peroxidation and a longer normal life-span. Oxidatively modified LDL is much more atherogenic than non-modified LDL. Oleic acid has, moreover, also been reported to have antiatherogenic protective effects on endothelial cells by reducing rates of intracellular generation of reactive oxygen species (ROS) and counteracting the activation of nuclear factor-kappaB." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875212/
Believe it or not, the above narrative covers almost all the bases. Although the Mediterranean style diet is not mentioned, that particular approach addresses two aspects of the harm caused by excessive polyunsaturated fatty acid intake. One is membrane imbalance that results in excessive inflammatory cell signaling. The other is peroxidation that causes damage to endothelial cells. The Mediterranean approach shifts protein intake from meat to plant sources. That reduces both linoleic acid and arachidonic acid intake. Swapping linoleic acid-rich culinary oils for olive oil (oleic acid) increases the likelihood that arachidonic acid molecules will be displaced from cell membranes and be oxidized for energy before they can be returned to take up a position vacated by another polyunsaturated fatty acid molecule.
This comment by Olaf Adam explains why it is important to reduce arachidonic acid intake early in life.
"Our studies on healthy volunteers were carried out with formula diets and allowed a precisely defined supply of arachidonic acid over a period of 6 weeks. These studies have shown that the exclusion of arachidonic acid from the diet (vegan diet) causes a progressive decrease of this fatty acid from 11 + 3% of the total fatty acids in the cholesterol esters of the plasma to 8 + 2% after 6 weeks. The later studies on patients with rheumatoid arthritis have shown that an intake of arachidonic acid amounting to not more than 80 mg/day does not increase the concentration of arachidonic acid in the phospholipids of the plasma and in the erythrocyte lipids. From these findings I have concluded that the body's own production of arachidonic acid is around 80 mg per day. This means that the Western Diet provides approximately 2.5 to 5 times the estimated need for arachidonic acid.
"This intake that is higher than the requirement primarily has no negative consequences. We know from many studies that the 'silent inflammation' characteristic for the prevalent diseases of western societies has a latency period of more than 10 years before the consequences such as arteriosclerosis and myocardial infarction become apparent. The body is evidently able to avert the consequences of an unfavorable diet for a long time. To do this, there are numerous regulatory options, such as substrate or product inhibition in the case of enzymes or the inhibition of transport to or incorporation into cells. Arachidonic acid has a very special metabolic pathway that offers possibilities for regulating absorption from the intestine, transport in the chylomicrons, metabolism via the enzymes involved and also for incorporation into the cells. For example, we have found a completely different efficiency for the uptake of arachidonic acid into the cell membrane for platelets compared to erythrocytes or granulocytes. It is therefore very likely that regulation options on the metabolic pathway of arachidonic acid can, to a certain extent, compensate for changes in intake."
"Only when too much arachidonic acid is present in the food for a prolonged time do these protective mechanisms apparently fail and inflammation and the manifestation of lifestyle diseases is seen. This explains the long latency period with which the diseases of civilization occur."
(excerpt from September 5, 2021 message from Olaf Adam, MD, PhD.)
When one consumes polyunsaturated fatty acids in amounts significantly in excess of biological requirements, they accumulate in adipose tissue. "While obesity is linked to cancer risk, no studies have explored the consequences of body mass index (BMI) on fatty acid profiles in breast adipose tissue and on breast tumor aggressiveness indicators... BMI impact was analyzed by age subgroups to overcome the age effect. BMI increase is associated with LC-PUFAs n-6 accumulation, including arachidonic acid. Positive correlations between BMI and several LC-PUFAs n-6 were observed, as well as a strong imbalance in the LC-PUFAs n-6/n-3 ratio." https://www.mdpi.com/2227-9059/10/5/995
"Fatty acid composition in the Western diet has shifted from saturated to polyunsaturated fatty acids (PUFAs), and specifically to linoleic acid (LA, 18:2), which has gradually increased in the diet over the past 50 y to become the most abundant dietary fatty acid in human adipose tissue." https://pubmed.ncbi.nlm.nih.gov/35312372/
More evidence: "Obesity sometimes seems protective in disease. This obesity paradox is predominantly described in reports from the Western Hemisphere during acute illnesses. Since adipose triglyceride composition corresponds to long-term dietary patterns, we performed a meta-analysis modeling the effect of obesity on severity of acute pancreatitis, in the context of dietary patterns of the countries from which the studies originated. Increased severity was noted in leaner populations with a higher proportion of unsaturated fat intake." https://pubmed.ncbi.nlm.nih.gov/33514548/
I was going to check with you about citing you in my substack but then i couldn't find your email address. i'm in the process of changing mine from jditrag@zoomnet.net to john @drditraglia.com. But then i figured i didn't say anything that would be a problem for you.
One aspect of lipid science that needs further elucidation is the toxicity problem. All polyunsaturated fatty acids are biologically active molecules as noted in this comment by Norwegian animal science researchers.
"Because arachidonic acid (AA) competes with EPA and DHA as well as with LA, ALA and oleic acid for incorporation in membrane lipids at the same positions, all these fatty acids are important for controlling the AA concentration in membrane lipids, which in turn determines how much AA can be liberated and become available for prostaglandin biosynthesis following phospholipase activation. Thus, the best strategy for dampening prostanoid overproduction in disease situations would be to reduce the intake of AA, or reduce the intake of AA at the same time as the total intake of competing fatty acids (including oleic acid) is enhanced, rather than enhancing intakes of EPA and DHA only. Enhancement of membrane concentrations of EPA and DHA will not be as efficient as a similar decrease in the AA concentration for avoiding prostanoid overproduction."
"Combining reduction of the intake of AA with enhancement of the intake of oleic acid will, moreover, also be a better strategy for reducing the total extent of in vivo lipid peroxidation, rather than adding more EPA (with 5 double bonds) and DHA (with 6 double bonds) to a diet already over-abundant in arachidonic acid and linoleic acid. A reduction of the dietary ratio of total polyunsaturated fatty acids to oleic acid will not only make plasma lipoproteins less vulnerable to oxidation, but must also be expected to lead to reduction of the rate of formation of mutagenic aldehydes that arise as secondary products of lipid peroxidation, such as malondialdehyde, crotonaldehyde, acrolein and 4-hydroxynonenal. High rates of production of these mutagenic aldehydes must be expected simultaneously to lead to enhancement of the risk of various forms of cancer, and enhancement of the rate of mitochondrial DNA aging, which could lead to earlier onset of various age-associated degenerative diseases perhaps including type 2 diabetes. The degree of fatty acid unsaturation of mitochondrial membrane lipids has been found to be one of those biochemical parameters that are most strongly correlated with longevity, when different species of mammals and birds are compared, with a low degree of fatty unsaturation being correlated with less lipid peroxidation and a longer normal life-span. Oxidatively modified LDL is much more atherogenic than non-modified LDL. Oleic acid has, moreover, also been reported to have antiatherogenic protective effects on endothelial cells by reducing rates of intracellular generation of reactive oxygen species (ROS) and counteracting the activation of nuclear factor-kappaB." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875212/
Believe it or not, the above narrative covers almost all the bases. Although the Mediterranean style diet is not mentioned, that particular approach addresses two aspects of the harm caused by excessive polyunsaturated fatty acid intake. One is membrane imbalance that results in excessive inflammatory cell signaling. The other is peroxidation that causes damage to endothelial cells. The Mediterranean approach shifts protein intake from meat to plant sources. That reduces both linoleic acid and arachidonic acid intake. Swapping linoleic acid-rich culinary oils for olive oil (oleic acid) increases the likelihood that arachidonic acid molecules will be displaced from cell membranes and be oxidized for energy before they can be returned to take up a position vacated by another polyunsaturated fatty acid molecule.
This comment by Olaf Adam explains why it is important to reduce arachidonic acid intake early in life.
"Our studies on healthy volunteers were carried out with formula diets and allowed a precisely defined supply of arachidonic acid over a period of 6 weeks. These studies have shown that the exclusion of arachidonic acid from the diet (vegan diet) causes a progressive decrease of this fatty acid from 11 + 3% of the total fatty acids in the cholesterol esters of the plasma to 8 + 2% after 6 weeks. The later studies on patients with rheumatoid arthritis have shown that an intake of arachidonic acid amounting to not more than 80 mg/day does not increase the concentration of arachidonic acid in the phospholipids of the plasma and in the erythrocyte lipids. From these findings I have concluded that the body's own production of arachidonic acid is around 80 mg per day. This means that the Western Diet provides approximately 2.5 to 5 times the estimated need for arachidonic acid.
"This intake that is higher than the requirement primarily has no negative consequences. We know from many studies that the 'silent inflammation' characteristic for the prevalent diseases of western societies has a latency period of more than 10 years before the consequences such as arteriosclerosis and myocardial infarction become apparent. The body is evidently able to avert the consequences of an unfavorable diet for a long time. To do this, there are numerous regulatory options, such as substrate or product inhibition in the case of enzymes or the inhibition of transport to or incorporation into cells. Arachidonic acid has a very special metabolic pathway that offers possibilities for regulating absorption from the intestine, transport in the chylomicrons, metabolism via the enzymes involved and also for incorporation into the cells. For example, we have found a completely different efficiency for the uptake of arachidonic acid into the cell membrane for platelets compared to erythrocytes or granulocytes. It is therefore very likely that regulation options on the metabolic pathway of arachidonic acid can, to a certain extent, compensate for changes in intake."
"Only when too much arachidonic acid is present in the food for a prolonged time do these protective mechanisms apparently fail and inflammation and the manifestation of lifestyle diseases is seen. This explains the long latency period with which the diseases of civilization occur."
(excerpt from September 5, 2021 message from Olaf Adam, MD, PhD.)
When one consumes polyunsaturated fatty acids in amounts significantly in excess of biological requirements, they accumulate in adipose tissue. "While obesity is linked to cancer risk, no studies have explored the consequences of body mass index (BMI) on fatty acid profiles in breast adipose tissue and on breast tumor aggressiveness indicators... BMI impact was analyzed by age subgroups to overcome the age effect. BMI increase is associated with LC-PUFAs n-6 accumulation, including arachidonic acid. Positive correlations between BMI and several LC-PUFAs n-6 were observed, as well as a strong imbalance in the LC-PUFAs n-6/n-3 ratio." https://www.mdpi.com/2227-9059/10/5/995
"Fatty acid composition in the Western diet has shifted from saturated to polyunsaturated fatty acids (PUFAs), and specifically to linoleic acid (LA, 18:2), which has gradually increased in the diet over the past 50 y to become the most abundant dietary fatty acid in human adipose tissue." https://pubmed.ncbi.nlm.nih.gov/35312372/
More evidence: "Obesity sometimes seems protective in disease. This obesity paradox is predominantly described in reports from the Western Hemisphere during acute illnesses. Since adipose triglyceride composition corresponds to long-term dietary patterns, we performed a meta-analysis modeling the effect of obesity on severity of acute pancreatitis, in the context of dietary patterns of the countries from which the studies originated. Increased severity was noted in leaner populations with a higher proportion of unsaturated fat intake." https://pubmed.ncbi.nlm.nih.gov/33514548/
So, to protect your health, choose foods with a low polyunsaturated fatty acid profile. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166560/
I was going to check with you about citing you in my substack but then i couldn't find your email address. i'm in the process of changing mine from jditrag@zoomnet.net to john @drditraglia.com. But then i figured i didn't say anything that would be a problem for you.