skip to main |
skip to sidebar
I noticed something strange when I was poring over data about the Inuit last month. Modern Inuit who have adopted Western food habits get fat, they get diabetes... but they don't get heart attacks. This was a paradox to me at the time, because heart disease mortality typically comes along with the cluster of modern, non-communicable diseases I call the "diseases of civilization".
One of the interesting things about the modern Inuit diet is it's most often a combination of Western and traditional foods. For example, they typically use white flour and sugar, but continue to eat seal oil and fish. Both seal oil and fish are a concentrated source of long-chain omega-3 (n-3) fatty acids.The 'paradox' makes much more sense to me now that I've seen this:
It's from the same paper as the graphs in the last post. Note that it doesn't take much n-3 to get you to the asymptote. Here's another one that might interest you:
The finding in this graph is supported by the Lyon diet heart study, which I'll describe below. One more graph from a presentation by Dr. Lands, since I began by talking about the Inuit:
Cardiovascular disease mortality tracks well with the n-6 content of blood plasma, both across populations and within them. You can see modern Quebec Inuit have the same low rate of CVD mortality as the Japanese. The five red triangles are from MRFIT, a large American intervention trial. They represent the study participants divided into five groups based on their plasma n-6. Note that the average percentage of n-6 fatty acids is very high, even though the trial occurred in the 1970s! Since n-3 and n-6 fats compete for space in human tissue, it makes sense that the Inuit are protected from CVD by their high n-3 intake. [Update: I don't read too much into this graph because there are so may confounding variables. It's an interesting observation, but take it with a grain of salt.. SJG 2011].
Now for a little mechanism. Dr. Lands' hypothesis is that a high n-6 intake promotes a general state of inflammation in the body. The term 'inflammation' refers to the chronic activation of the innate immune system. The reason is that n-3 and n-6 fats are precursors to longer-chain signaling molecules called eicosanoids. In a nutshell, eicosanoids produced from n-6 fatty acids are more inflammatory and promote thrombosis (clotting) more than those produced from n-3 fatty acids. Dr. Lands is in a position to know this, since he was one of the main researchers involved in discovering these mechanisms. He points out that taking aspirin to 'thin' the blood and reduce inflammation (by inhibiting inflammatory eicosanoids) basically puts a band-aid over the problem caused by excess n-6 fats to begin with. [Update- this mechanism turns out not to be so straightforward. SJG 2011]
The Lyon Diet Heart Study assessed the effect of n-3 fat supplementation on CVD risk. The four-year intervention involved a number of diet changes designed to mimic the American Heart Association's concept of a "Mediterranean diet". The participants were counseled to eat a special margarine that was high in n-3 from alpha-linolenic acid. Overall PUFA intake decreased, mostly due to n-6 reduction, and n-3 intake increased relative to controls. The intervention caused a 70% reduction in cardiac mortality and a large reduction in all-cause mortality, a smashing success by any measure.
In a large five-year intervention trial in Japan, JELIS, patients who took EPA (a long-chain n-3 fatty acid) plus statins had 19% fewer cardiac events than patients taking statins alone. I don't know why you would give EPA by itself when it occurs with DHA and alpha-linolenic acid in nature, but it did nevertheless have a significant effect. Keep in mind that this trial was in Japan, where they already have a much better n-6/n-3 ratio than in Western nations.
In my opinion, what all the data (including a lot that I haven't included) point to is that a good n-6 to n-3 ratio may be important for vibrant health and proper development. In the next post, I'll talk about practical considerations for achieving a good ratio.
I noticed something strange when I was poring over data about the Inuit last month. Modern Inuit who have adopted Western food habits get fat, they get diabetes... but they don't get heart attacks. This was a paradox to me at the time, because heart disease mortality typically comes along with the cluster of modern, non-communicable diseases I call the "diseases of civilization".
One of the interesting things about the modern Inuit diet is it's most often a combination of Western and traditional foods. For example, they typically use white flour and sugar, but continue to eat seal oil and fish. Both seal oil and fish are a concentrated source of long-chain omega-3 (n-3) fatty acids.The 'paradox' makes much more sense to me now that I've seen this:
It's from the same paper as the graphs in the last post. Note that it doesn't take much n-3 to get you to the asymptote. Here's another one that might interest you:
The finding in this graph is supported by the Lyon diet heart study, which I'll describe below. One more graph from a presentation by Dr. Lands, since I began by talking about the Inuit:
Cardiovascular disease mortality tracks well with the n-6 content of blood plasma, both across populations and within them. You can see modern Quebec Inuit have the same low rate of CVD mortality as the Japanese. The five red triangles are from MRFIT, a large American intervention trial. They represent the study participants divided into five groups based on their plasma n-6. Note that the average percentage of n-6 fatty acids is very high, even though the trial occurred in the 1970s! Since n-3 and n-6 fats compete for space in human tissue, it makes sense that the Inuit are protected from CVD by their high n-3 intake. [Update: I don't read too much into this graph because there are so may confounding variables. It's an interesting observation, but take it with a grain of salt.. SJG 2011].
Now for a little mechanism. Dr. Lands' hypothesis is that a high n-6 intake promotes a general state of inflammation in the body. The term 'inflammation' refers to the chronic activation of the innate immune system. The reason is that n-3 and n-6 fats are precursors to longer-chain signaling molecules called eicosanoids. In a nutshell, eicosanoids produced from n-6 fatty acids are more inflammatory and promote thrombosis (clotting) more than those produced from n-3 fatty acids. Dr. Lands is in a position to know this, since he was one of the main researchers involved in discovering these mechanisms. He points out that taking aspirin to 'thin' the blood and reduce inflammation (by inhibiting inflammatory eicosanoids) basically puts a band-aid over the problem caused by excess n-6 fats to begin with. [Update- this mechanism turns out not to be so straightforward. SJG 2011]
The Lyon Diet Heart Study assessed the effect of n-3 fat supplementation on CVD risk. The four-year intervention involved a number of diet changes designed to mimic the American Heart Association's concept of a "Mediterranean diet". The participants were counseled to eat a special margarine that was high in n-3 from alpha-linolenic acid. Overall PUFA intake decreased, mostly due to n-6 reduction, and n-3 intake increased relative to controls. The intervention caused a 70% reduction in cardiac mortality and a large reduction in all-cause mortality, a smashing success by any measure.
In a large five-year intervention trial in Japan, JELIS, patients who took EPA (a long-chain n-3 fatty acid) plus statins had 19% fewer cardiac events than patients taking statins alone. I don't know why you would give EPA by itself when it occurs with DHA and alpha-linolenic acid in nature, but it did nevertheless have a significant effect. Keep in mind that this trial was in Japan, where they already have a much better n-6/n-3 ratio than in Western nations.
In my opinion, what all the data (including a lot that I haven't included) point to is that a good n-6 to n-3 ratio may be important for vibrant health and proper development. In the next post, I'll talk about practical considerations for achieving a good ratio.
Another interesting study that Dr. Hibbeln sent me is about the link between maternal seafood consumption and neurodevelopmental outcomes in children. The study is about as powerful as epidemiology gets, with an enrollment of 11,875 mothers. The bottom line is short and sweet: compared to the children of mothers who ate 340 grams or more of fish per week, children whose mothers ate very little fish had an increased risk of low verbal intelligence, poor social behavior, poor motor skills, poor communication skills, and poor social development. These associations remained after adjusting for 28 potential confounders, including social status, level of education, stressful life events, smoking, alcohol, and several others.In support of this association, in another study the four-year-old children of mothers who were given DHA and arachidonic acid supplements had higher IQs than those given "placebo" (corn oil). There have been a number of trials of varying quality that have shown varying results with n-3 supplementation, so I'll leave you to decide what you think of this. A 2007 review I found on n-3 supplementation and brain development states that "the evidence for potential benefits of LCPUFA [long-chain polyunsaturated fatty acid] supplementation is promising but yet inconclusive". I do think it's interesting to note that the brain has the highest concentration of long-chain n-3 fats of any organ, and eating n-3 fats in the form of fish, fish oil or cod liver oil increases the amount in tissues. Eating too much n-6 depletes the brain of DHA and adversely affects neuron development in piglets. n-3 deficiency affects the release of serotonin (a neurotransmitter) in rat brains.Put it all together, including the data from the last two posts, and I think there's some evidence that a good balance of n-3 to n-6 fatty acids is important for optimal brain function and perhaps development.
Another interesting study that Dr. Hibbeln sent me is about the link between maternal seafood consumption and neurodevelopmental outcomes in children. The study is about as powerful as epidemiology gets, with an enrollment of 11,875 mothers. The bottom line is short and sweet: compared to the children of mothers who ate 340 grams or more of fish per week, children whose mothers ate very little fish had an increased risk of low verbal intelligence, poor social behavior, poor motor skills, poor communication skills, and poor social development. These associations remained after adjusting for 28 potential confounders, including social status, level of education, stressful life events, smoking, alcohol, and several others.In support of this association, in another study the four-year-old children of mothers who were given DHA and arachidonic acid supplements had higher IQs than those given "placebo" (corn oil). There have been a number of trials of varying quality that have shown varying results with n-3 supplementation, so I'll leave you to decide what you think of this. A 2007 review I found on n-3 supplementation and brain development states that "the evidence for potential benefits of LCPUFA [long-chain polyunsaturated fatty acid] supplementation is promising but yet inconclusive". I do think it's interesting to note that the brain has the highest concentration of long-chain n-3 fats of any organ, and eating n-3 fats in the form of fish, fish oil or cod liver oil increases the amount in tissues. Eating too much n-6 depletes the brain of DHA and adversely affects neuron development in piglets. n-3 deficiency affects the release of serotonin (a neurotransmitter) in rat brains.Put it all together, including the data from the last two posts, and I think there's some evidence that a good balance of n-3 to n-6 fatty acids is important for optimal brain function and perhaps development.
The theory advanced by Dr. Lands and Hibbeln is that the ratio of omega-6 to omega-3 fatty acids in the diet is the crucial factor for mental and physical health, rather than the absolute amount of each. Omega-6 and -3 fats are essential long-chain polyunsaturated fatty acids. The number refers to the position of the double bond near the methyl end of the carbon chain.The ratio of omega-6 to omega-3 (hereafter, n-6 and n-3) in the diet determines the ratio in tissues. Since these molecules have many cellular roles, it doesn't stretch the imagination that they could have an effect on health. Hunter-gatherer and healthy non-industrial cultures typically have a favorable ratio of n-6 to n-3, 2:1 or less. In the US, the ratio is currently about 17:1 due to modern vegetable oils.DHA, a long-chain n-3 fatty acid, is concentrated in neuronal synapses (the connections between neurons) and is required for the normal functioning of neurons. n-6 fats compete with n-3 fats for space in cellular membranes (which have a fixed amount of total polyunsaturated fat), so a high intake of n-6 fats, particularly linoleic acid, displaces n-3 fatty acids. Lower tissue levels of DHA and total n-3 correlate with measures of hostility in cocaine addicts. Feeding mice a diet high in linoleic acid increases aggressive behavior, and increses the likelihood of rats to kill mice.If the ratio of n-6 to n-3 in the diet predicts psychiatric problems, we'd expect to see an association with n-3 intake as well. Let's take a look:
This is homicide mortality vs. n-3 intake for 24 countries, published here. The association is significant (p> 0.001) even without correcting for n-6 intake. Of course, one could see this as a cloud of points with a few well-placed outliers. Here are some closer associations from the same paper:
It's clear that both a high n-6 intake and a low n-3 intake correlate with negative psychiatric outcomes. Together, the data are consistent with the hypothesis that the ratio of n-6 to n-3 impacts brain function. Dr. Hibbeln and Dr. Lands do not claim that this ratio is the sole determinant of psychiatric problems, only that it is a factor. Now to address the big criticism that was brought up by very astute readers of the last post, namely, that the data were purely correlative. Believe me, I wouldn't even have posted on this topic if I didn't have intervention data to back it up. In addition to the animal data I mentioned above, here are more studies that support a causal role of fatty acid balance in psychiatric problems:Most of those were placebo-controlled trials. If we can see a significant effect of n-3 supplementation in short-term trials, imagine how well it would work as a long-term preventive measure.
It's from the same paper as the graphs in the last post. Note that it doesn't take much n-3 to get you to the asymptote. Here's another one that might interest you:
The finding in this graph is supported by the Lyon diet heart study, which I'll describe below. One more graph from a presentation by Dr. Lands, since I began by talking about the Inuit:
