Why a fat brain made us more vulnerable to heart disease

Natural selection granted us large brains. The evolutionary cost is having to feed them. The human brain's high-energy demands led to development of a strong preference for fat. We consume more fat than any other primate on average. We are also adapted to more easily digest and metabolize fats.

There are two major kinds of fat that our brains depend on most for its development and regular maintenance. These are the long-chain polyunsaturated fatty acids (LC-PUFAs), omega-3 docosahexaenoic acid (DHA) and omega-6 arachidonic (AA). These two LC-PUFAs can't be made de novo, making them essential in the diet. DHA and AA are supplied by seafood, eggs, or animals. They can also be supplied as their 18-carbon precursors alpha-linolenic acid (ALA) and linoleic acid (LA), found mainly in plants and their seeds.

ALA and LA precursors require conversion to become long-chained through a series of steps of desaturation and elongation. In particular, delta-5 and delta-6 fatty acid desaturases build onto the carboxyl end of the carbon chains of the ALA and LA by introducing double bonds. These converting enzymes are rate-limiting.

The rate-limiting enzymes are encoded into the genome by FADS1 and FADS2. The FADS region has been of special interest to researchers because of variations in single-nucleotide polymorphisms (SNPs) that could lend clues about human evolution including our larger brains. Yet, to date, there have not existed any studies evaluating FADS mutations among humans and related species.

Now, researchers from Uppsala University, in Sweden, along with scientists at MIT, Harvard, and major European Universities, have found genetic variation in the FADS region in present-day humans that made them uniquely adapted to biosynthesize DHA and AA. The same adaptations could also help explain why some ethnicities have a higher susceptibility to chronic disease today.

The international team set out to investigate by using genomic data from contemporary human populations, archaic hominins, and more distant primates. They used SNP genotype data from more than 5,600 individuals across five European population cohorts. They evaluated mutations in the FADS region that are strongly associated with omega-3 and omega-6 fats.

Two common FADS haplotypes

Among present-day humans, they report, exist two common FADS haplotypes, or groups of alleles defined across a set of 28 SNPs, that are "dramatically different in their efficiency" to biosynthesize DHA and AA from he shorter ALA and LA.

The 28 SNPs of two main haplotypes (A in red, D in blue) and nucleotides of species.

Haplotype A, limited in conversion efficiency, appeared nearly 606 thousand years ago. Rhesus monkeys, chimpanzees, gorillas, and Denisovans all bear haplotypes "very similar" to haplotype A. Neandertals too, although based on incomplete sequences, have similar haplotypes to haplotype A.

Haplotype D, having greater conversion efficiency, appeared somewhere between the lineage split with Neandertals. That was around 500 thousand years ago and before the exodus from Africa some 50 to 100 thousand years ago. Both haplotypes must've been present during the exodus or else we wouldn't see the existence of them in modern humans today.

The researchers speculate that "a very rapid increase in brain size of hominoids" probably involved selection and the increased frequency of haplotype D. That does not mean that haplotype D had any direct effect on brain size, but that it was highly advantageous in environments where there was limited access to AA and DHA to feed the brain.

Haplotypes A and D in Present-day Humans

Nowadays, the researchers found, nearly all individuals of African descent had haplotype D. The high frequency indicates positive selection for the haplotype with more efficient conversion in the face of limited availability of LC-PUFAs in early Africa.

On the other hand, nearly all Native Americans had haplotype A. The reason, the researchers propose, may be because of a "bottleneck effect in the colonization of the American continent, possibly in combination with relaxation of the selective pressure as a result of a diet higher in essential LC-PUFAs."

The data are mixed in those descended from Europe, Oceania, East Asia, who are reported to have haplotype D at a greater frequency.

The frequencies of A (blue), D (red), and mixed (gray) haplotypes.

Health Implications


How can the knowledge of these haplotypes inform guidance on diet? The differences in haplotypes may explain why individuals of specific ethnicities may be more susceptible to chronic disease compared to others.

Individuals with haplotype D biosynthesize more AA and DHA than individuals with haplotype A. While this adaptation may have been useful on the African savannah, the researchers propose it has drawbacks as a "thrifty genotype" in our modern world. As plentiful as LA (from corn and soy) is in the Western diet, haplotype D may lead to higher levels of AA-derived pro-inflammatory eicosanoids, which raise the risk of atherosclerosis and coronary artery disease.

A different set of problems are presented for individuals with haplotype A. These individuals may be protected against a high-LA diet to a degree because of limited conversion to AA. However, they are more dependent on animal foods for adequate amounts of DHA due to inability to convert sufficient ALA to the longer-chained counterpart on a more plant-based diet.

The researchers propose, "FADS genotyping should be included as a diagnostic for dietary recommendations."

As genetic testing is not yet widely available, here's a more viable solution for the sake of a large human brain and a genome not well adapted to a high-LA diet: eat less LA; and, eat more foods enriched in long-chained omega-3s such as eggs, grass-fed animals, and seafood.

Reference

Ameur et. al. Genetic Adaptation of Fatty-Acid Metabolism: A Human-Specific Haplotype Increasing the Biosynthesis of Long-Chain Omega-3 and Omega-6 Fatty Acids. American Journal of Human Genetics, April 12, 2012 DOI: 10.1016/j.ajhg.2012.03.014

Related Posts

• Omega-3 Overview and Book Review of "Queen of Fats" by Susan Allport
• Boost omega-3 by reducing omega-6
• How diet shaped human evolution

How diet shaped human evolution

Anyone who is keenly interested in having a better understanding of why we eat what we eat as human beings should take an hour or so to watch this introductory talk given by anthropologist Teresa Steele, of UC Davis, given at the California Academy of Sciences on the topic of evolution of the human diet.

I found her talk fascinating, especially because I've been highly interested in how the use of fire and aquatic animals may have played a part in fueling human brain growth, so I ended up taking copious notes. I should note that there isn't anything new presented here, but Steele is excellent at presenting the chronology. If you don't have an hour to watch, then just see my notes below chapter by chapter from "Australopithecus to agriculture."

Human diet is unique among apes

Steele finds that diet is central to her research. "If we want to live, we have to eat," she says. Food is what ultimately supports demographic populations. One thing that is unique about humans in comparison to other apes is a long childhood, a long learning period, that is required for acquiring the knowledge necessary to become successful foragers in a wide environment. After all, humans have exploited almost every nutrient resource in their short time on the Earth.

Another unique thing is how much meat we consume. A large portion of our calories comes from meat. Unlike chimpanzees, who eat the most meat among apes, human eat about 10 times more, Steele said. And we eat animals that are usually larger than us like wildebeasts, reindeer, and mammoths. Steele shows a graph comparing chimp diets to that of tropical hunter gatherers groups, who typically eat little meat. Other hunter-gatherers of the North like the Inuit eat a diet almost entirely of meat. In general, humans specialize in acquiring nutrient-dense foods meats, tubers, and nuts, while chimps select non-nutrient dense like leaves that are more easily collected.

Research themes

When did these differences evolve? Steele presents us with her research themes, which include the following:

• Meat eating. We are consuming animals that are larger than ourselves like wildebeast, reindeer, horses, and so on. Chimpanzees hunt for colobus monkeys, birds, and small amphibians. So when did meat eating appear and when did the transition occur to eating animals larger than us?
• Hunting technology. What technology did humans use to acquire large animals? Spears, bows and arrows, projectile technology? These are complex, so they can represent greater cognition. When did they occur?
• Intensification of resource use, including agriculture. This happened much more recently.

Methods of Study

What methods does Steele use to construct ancient human diets? She says that zooarchaeology and tool analyses gives us a window into ancient demographies. There are stone, bone and antler tools. And, on occasion, organic wood and plant tools are preserved. Also, biological anthropology helps tell us more such as skeletal morphology and bone chemistry.

Lucy's diet

Steele introduces the diet of Lucy's species first, Austrolopithecus afarensis of 3.7-2.8 mya, who ate a flexible diet suitable for a variety of habitats.

The skeletal biomechanics and dental structure suggest they ate mostly soft fruits and occasional hard seeds. However, Steele says we assume that they may have eaten some meat because chimps eat meat, but it's unclear just how much.

She points out that, recently, there was a groundbreaking discovery published in Nature (and reported in Scientific American by the science writer Kate Wong (Twitter: @katewong) ) of cut-marked bones in Dikika, Ethiopia suggesting Lucy's species even used stone tools for eating meat.

"This has opened up a window," Steele says for more research, especially in the possibility of stone tool use for extracting nutrients from carcasses of smaller animals. It's worth noting that no stone artifacts were found associated with the cut-marked bones (paleoanthropologist John Hawks (Twitter: @johnhawks) has written more about this topic on his blog).

Cut-marked bones 2.5 million years ago

Typically, a discussion of human diet begins at about 2.5 mya when there is an abundance of cut-marked bones (such as the jaw of a wildebeest) and percussion marks from marrow extraction. Marrow has been an important human resource for nutrients up until modern times because it's high in fat, high in calories.

There is also evidence of Oldowan artifacts (hominin stone tools) available so we know what they were using to get to the marrow.

Then, at about 1.8 mya there are a lot more assemblages, more stone tools, as found in Olduvai Gorge, Tanzania, by Mary Leaky. There are also lots of large bodies bovids and carnivores on the landscape. Steele asks, How did these ancient hominids acquire these large carcasses? Is it conceivable that they could've brought down a wildebeast with just tools?

This is where we get into a discussion of scavenging versus hunting, she said. A related discussion is what percentage of the diet was meat-based versus plant-based. Also, were these ancient hominins practicing passive scavenging getting to a carcass to get the last scraps of meat or breaking open bones for marrow. Or was it active scavenging, chasing off carnivores?

These are all active areas of research. For answers, researchers look in locations of lakeside margins. Bovids came to drink, carnivores know this, we look into these locations to try and reconstruct the foraging.

Aquatic animals

Published recently in the springtime, was a paper suggesting that 1.9 mya in East Turkana, there's evidence of Oldowan foraging of carcasses of aquatic animals like crocodiles and turtles. Steele shows a cut marks on a toe bone of a croc, turtle shells and catfish bones.

"For the first time, we see exploitation of aquatic resources highlighting the diversity of diet. Hominins are very opportunistic, exploiting whatever was available," Steele said.

"This also raises a challenge as with cut-marked bones with Dekika, to try to see if there are cut-marks on similar bones," Steele explains. "The small animal component has been overlooked so we may need to look closer."

Steele also discusses another interesting aspect of using aquatic resources (which will interest any nutritionist like myself). The aquatic resources would have been an easier way to access long-chain omega-3 fatty acids, which are also present in organ meats and brain tissues of large animals.

"The long-chain unsaturated fatty acids are needed for brain growth," she explained. "At this time period we do see an expansion of brain sizes, so perhaps there's a relationship here. We need more data, more examples where we see brain expansion with this kind of diet."

Archeulean hunting and scavenging

Moving more recently in time, we see Homo erectus, hominins of larger body size, and who were first to populate Eurasia 1.6 mya to 285 kya. Were they hunting or actively scavenging? This is unclear, but earlier in Archeulan, we see evolution of technology.

Tear-drop shaped hand axes appear and body size changes. The humans are obviously living in social groups. An illustration she uses takes the liberty of showing piles of plant remains used to make wooden spears. The plant use is unknown.

There are a large number of animal bones with few cut marks. So, the question remains, were hominins still minor players as carnivores, simply cutting off limbs and eating elsewhere. The challenge is finding places away from water sites such as in caves.

Also, we start asking questions about use of fire at this time period.

Wood spears

At around 400 kya, Steele shares that there are one or two examples of exceptional preservation of organic materials such as wooden spears (survived in an oxygen-poor environments from marshes of Germany). They are more likely to be thrusting spears. They have been fire-hardened, sharpened, so it indicates use of fire.

Fire is really useful for warmth, protection from predators, for cooking and cooking really changes the nature of food. It helps make inedible foods edible, releases nutrients for our digestive systems. But fire doesn't preserve well.

The earliest known site where fire is documented is in Israel, dated to 780 kya. "We have an indicator of fire use and plant remains. They're preserve better once charred in archaeological sites," Steele says. "We don't find it common until about 300,000 years ago." This is between Oldowan and modern behavior in the Archeulian.

Neandertals

About 200 kya came the Neandertals and they were competent hunters and manufacturers of stone tools. Interestingly, despite these complex behaviors, they did not have as long a childhood. The Neandertals were able to pick up their abilities pretty early in life.

As part of her post-doc in Germany at Max Plank Institute, Steele worked with identifying species in archaeological sites where Neandertals hunted reindeer and bison. She showed antlers, elbows of reindeer fractured for extracting marrow, and examples of bones in discard piles due to little meat.

"We also see very little carnivore involvement and abundant human impacts, unlike the earlier where there was very heavy carnivore involvement meaning humans were hunting," she said. The Neandertals were dominant carnivores by this time.

Now we can ask about hunting strategy. Steele explains she uses a very low tech method: "We have a number of mandibles, so just looking at the eruption of teeth, we can reconstruct ages of animals." Also, reindeer are conveniently sexually dimorphic and because reindeer give birth at a moment in spring (babies are born at once) we can look at eruption of teeth to see if they're hunted. In a specific location, all ages are present, males and females, so it looks like the reindeer herd would have been slowed allowing the humans to hunt more of them.

Bone chemistry

Carbon isotopes tell us about the vegetation in the environment and nitrogen isotopes tell us about the trophic levels. Carnivores have more concentration of nitrogen. Animals that are aquatic even more nitrogen, so we can look at bone chemistry to reconstruct diet. There aren't much indicators of plant remains, but in a Neandertal tooth you see it's heavily etched by roots because of the acid of roots. The bone chemistry data put Neandertals right along the lines of other carnivores. The majority of protein came from meat (although not mentioned in the talk, new findings show they also practiced cannibalism, reported via science writer Carl Zimmer (Twitter: @carlzimmer)).

Hunting technology

How were the Neandertals doing the hunting? It appears they were using thrusting spears. We know this because it's possible to look at stone artifacts to see if they are aerodynamic or more asymetrical and lumpy for a thrusting spear. We can look at the breakage of the tip as well as the butt. In characteristic way we can look at the breakage.

Middle stone age in Africa 285,000

So while Neandertals are doing their thing in Europe, what's going on in Africa? In Africa, we have the middle stone age and humans who were morphologically similar to us. The big discussion in paleoanthropology is, How modern were they? Did they have symbolism? Were they just like us or behave more like Neandertals without as much symbolism?

In the middle stone age we have good evidence of hunting and burning. There was abundant burning. But, within the middle stone age, we see no evidence of consumption of fish. The people seem to be limited in capturing fish and birds, although there were people accessing coastal resources along the southern coast of Africa, eating a number of mollusks. Could mollusks have fueled brain growth and brought with it symbolic behavior? There were also a number of fireplaces. Did fire fuel brain growth (if you ask primatologist Richard Wrangham as I did last February, then the answer is a resounding "yes!")? This is something that requires further research.

Modern humans in Europe

In Europe about 40 to 10 kya, we have Upper Paleolithic with fully modern humans in Europe. They hunted large game similar to Neandertals and with projectile technology unlike Neandertals. People who were just like us in biology and behavior. This is when we see projectiles for the first time. We see the reconstruction of a spear thrower, with an adle addle.

These modern humans then also enjoyed a diverse diet with abundant small game like fish and flying birds. That's quite different than what their Neandertals cousins were doing, and what humans in Africa of the middle-stone age were doing.

We can also see this in the bone chemistry of the Upper Paleolithic humans. There was definitely protein coming in from aquatic sources, per the nitrogen values in the bones. It's also clear from the bone chemistry that modern humans were eating a much more diverse diet.

Plant use

Getting back to plant use, just recently in PNAS, an article was published about use of plants in Paleolithic times. Grindstones and pestles were used to grind starch grains, reeds, cattailes and ferns that have underground storage organs (roots). These grindstones pulverized the roots and perhaps made flour out of them. So, this is it, the diversity of diet that spread from Africa about 50 kya, and support for the hypothesis that humans replaced Neandertals because of flexibility of diet. Is this what allowed humans to be more successful?

Intensification of resource extraction, including agriculture

Bringing us into more recent time period to complete the story, 50kya humans colonized Europe and Asia and Australia. At around 15kya, they colonized the new world. So, by 10kya we have humans everywheere by 10kya other than Pacific islands and Antarctica. Diet tends to evolve and change. Humans don't stay focused on large game, and birds and fish. They intensify. What we see with intensification in the Holocene is the use of technology to extract nutrients from resources.

Steele shows pictures of mussel shells having accumulated over a short period of time. There was a heavier investment in technology. This creates a stable food supply that allows populations to grow. "We can see this in our local California native indians," she said. Just to highlight investment in technology, she shows slides on the natives' use of technology. "These are all the steps to take acorns and make it into something consumable. They're toxic, so you have to dry them, pulverize and leach them. It requires very heavy technological input."

The intensification brings with it the origins of agriculture at 10 kya. At 10kya we see changes in environment tha promote plant resources, a shift in global climate where there's more CO2, a more wet and stable environment, more admittable to plant production. People are becoming more dependent on smaller resources from agriculture. The fish, they help populations to grow and hunter-gatherer populations are more stable. It's clear from her slide that because of agriculture, there's an uptick in human population growth. Then, when industrialized agriculture arrives, there's an inflection point when we see a high rate of population growth. That's where we are today in the evolution of human diets. That's 4 million years (in 40 minutes).

Question 1: Why did humans replaced Neandertals?

The first question posed to Steele after her talk was about her thoughts were about why humans replaced Neandertals. She answered, "Yes, I think ultimately it's due to dietary differences." There's not much differences in species hunted, not so different butchery, but you do see a difference in stone artifacts and projectile points. The modern human tools were more reliable and accurate. They would've been able to obtain a larger number of reindeer, and been more consistent in hunting, along with having a more diverse diet.

The more ultimate explanation, however, was if it was cultural. Did modern humans have a more complex language? Could symbolism have allowed us to communicate in a more effective way, made our hunting more effective, that's where we're going now with the research. Language is fundamental, so if we can track where language evolved, then we'll find more answers?

Question 2: What conclusive evidence is there of cut marks?

The question asked to Steele reverted back 3.2 mya to how solid the evidence was of Australopithecus afarensis making cut marks. Steele answers that the cut marks are just as conclusive as later time periods. "If we are going to accept the later cut marks, then we have to accept the earlier," she said. "For me they're fine in terms of more recent assemblages. The challenge is to find more cut marks to see if it was widespread or a one-time thing. Who made them? Where are the stone tools?" That's the next project.

Question 3: What ratio of fatty acids in diet correspond to brain size?

Lastly, an audience member asked if recent work on long-chain omega-3s on mood disorders supports the theory that omega-3s from aquatic resources fueled brain growth. The quiestoner also mentions work by others on omega-3 to omega-6 ratios, which has changed since huntergatherer times (from 1:1-3 to 1:10 to 1:20). Could this be the reason that brain sizes are getting smaller?

Steele answers that, in general, there's body size reduction and brain size reduction. Hunter-gatherers of the anthropological record were quite robust. Now we see decrease in stature, brain size reducing, body size reducing. The change in body shape may be due to changes in diet. Whether it's omega-3/omega-6? Steele says she couldn't say for sure if that's the case.

(Note: Hat tip to @KeithNorris and @evolvify (see blog post here) for first alerting me to this new video via their tweets).

38 g of sardines or 2 fish oil softgels? Let us look at the numbers

The bar chart below shows the fat content of 1 sardine (38 g) canned in tomato sauce, and 2 fish oil softgels of the Nature Made brand. (The sardine is about 1/3 of the content of a typical can, and the data is from Nutritiondata.com. The two softgels are listed as the “serving size” on the Nature Made bottle.) Both the sardine and softgels have some vegetable oil added; presumably to increase their vitamin E content and form a more stable oil mix. This chart is a good reminder that looking at actual numbers can be quite instructive sometimes. Even though the chart focuses on fat content, it is worth noting that the 38 g sardine also contains 8 g of high quality protein.

If your goal with the fish oil is to “neutralize” the omega-6 fat content of your diet, which is most people’s main goal, you should consider this. A rough measure of the omega-6 neutralization “power” of a food portion is, by definition, its omega-3 minus omega-6 content. For the 1 canned sardine, this difference is 596 mg; for the 2 fish oil softgels, 440 mg. The reason is that the two softgels have more omega-6 than the sardine.

In case you are wondering, the canning process does not seem to have much of an effect on the nutrient composition of the sardine. There is some research suggesting that adding vegetable oil (e.g., soy) helps preserve the omega-3 content during the canning process. There is also research suggesting that not much is lost even without any vegetable oil being added.

Fish oil softgels, when taken in moderation (e.g., two of the type discussed in this post, per day), are probably okay as “neutralizers” of omega-6 fats in the diet, and sources of a minimum amount of omega-3 fats for those who do not like seafood. For those who can consume 1 canned sardine per day, which is only 1/3 of a typical can of sardines, the sardine is not only a more effective source of omega-3, but also a good source of protein and many other nutrients.

As far as balancing dietary omega-6 fats is concerned, you are much better off reducing your consumption of foods rich in omega-6 fats in the first place. Apparently nothing beats avoiding industrial seed oils in that respect. It is also advisable to eat certain types of nuts with high omega-6 content, like walnuts, in moderation.

Both omega-6 and omega-3 fats are essential; they must be part of one’s diet. The actual minimum required amounts are fairly small, probably much lower than the officially recommended amounts. Chances are they would be met by anyone on a balanced diet of whole foods. Too much of either type of fat in synthetic or industrialized form can cause problems. A couple of instructive posts on this topic are this post by Chris Masterjohn, and this one by Chris Kresser.

Even if you don’t like canned sardines, it is not much harder to gulp down 38 g of sardines than it is to gulp down 2 fish oil softgels. You can get the fish oil for $12 per bottle with 300 softgels; or 8 cents per serving. You can get a can of sardines for 50 cents; which gives 16.6 cents per serving. The sardine is twice as expensive, but carries a lot more nutritional value.

You can also buy wild caught sardines, like I do. I also eat canned sardines. Wild caught sardines cost about $2 per lb, and are among the least expensive fish variety. They are not difficult to prepare; see this post for a recipe.

I don’t know how many sardines go into the industrial process of making 2 fish oil softgels, but I suspect that it is more than one. So it is also probably more ecologically sound to eat the sardine.

Nuts by numbers: Should you eat them, and how much?

Nuts are generally seen as good sources of protein and magnesium. The latter plays a number of roles in the human body, and is considered critical for bone health. Nuts are also believed to be good sources of vitamin E. While there is a lot of debate about vitamin E’s role in health, it is considered by many to be a powerful antioxidant. Other than in nuts, vitamin E is not easily found in foods other than seeds and seed oils.

Some of the foods that we call nuts are actually seeds; others are legumes. For simplification, in this post I am calling nuts those foods that are generally protected by shells (some harder than others). This protective layer is what makes most people call them nuts.

Let us see how different nuts stack up against each other in terms of key nutrients. The quantities listed below are per 1 oz (28 g), and are based on data from Nutritiondata.com. All are raw. Roasting tends to reduce the vitamin content of nuts, often by half, and has little effect on the mineral content. Protein and fat content are also reduced, but not as much as the vitamin content.

These two figures show the protein, fat, and carbohydrate content of nuts (on the left); and the omega-6 and omega-3 fat content (on the right).

When we talk about nuts, walnuts are frequently presented in a very positive light. The reason normally given is that walnuts have a high omega-3 content; the plant form of omega-3, alpha-linolenic acid (ALA). That is true. But look at the large amount of omega-6 in walnuts. The difference between the omega-6 and omega-3 content in walnuts is about 8 g! And this is in only 1 oz of walnuts. That is 8 g of possibly pro-inflammatory omega-6 fats to be “neutralized”. It would take many fish oil softgels to achieve that.

Walnuts should be eaten in moderation. Most studies looking at the health effects of nuts, including walnuts, show positive results in short-term interventions. But they usually involve moderate consumption, often of 1 oz per day. Eat several ounces of walnuts every day, and you are entering industrial see oil territory in terms of omega-6 fats consumption. Maybe other nutrients in walnuts have protective effects, but still, this looks like dangerous territory; “diseases of civilization” territory.

A side note. Focusing too much on the omega-6 to omega-3 ratio of individual foods can be quite misleading. The reason is that a food with a very small amount of omega-6 (e.g., 50 mg) but close to zero omega-3 will have a very high ratio. (Any number divided by zero yields infinity.) Yet, that food will contribute little omega-6 to a person’s diet. It is the ratio at the end of the day that matters, when all foods that have been eaten are considered.

The figures below show the magnesium content of nuts (on the left); and the vitamin E content (on the right).

Let us say that you are looking for the best combination of protein, magnesium, and vitamin E. And you also want to limit your intake of omega-6 fats, which is a very wise thing to do. Then what is the best choice? It looks like it is almonds. And even they should be eaten in small amounts, as 1 oz has more than 3 g of omega-6 fats.

Macadamia nuts don’t have much omega-6; their fats are mostly monounsaturated, which are very good. Their protein to fat ratio is very low, and they don’t have much magnesium or vitamin E. Coconuts (i.e., their meat) have mostly medium-chain saturated fats, which are also very good. Coconuts have little protein, magnesium, and vitamin E. If you want to increase your intake of healthy fats, both macadamia nuts and coconuts are good choices, with macadamia nuts providing about 3 times more fat.

There are many other dietary sources of magnesium around. In fact, magnesium is found in many foods. Examples are, in approximate descending order of content: salmon, spinach, sardine, cod, halibut, banana, white potato, sweet potato, beef, chicken, pork, liver, and cabbage. This is by no means a comprehensive list.

As for vitamin E, it likes to hide in seeds. While it may be a powerful antioxidant, I wonder whether Mother Nature really had it “in mind” as she tinkered with our DNA for the last few million years.

What happens on a high omega-6 diet

A while back I wrote a review of Queen of Fats: Why Omega-3s Were Removed from the Western Diet and What We Can Do about Them. Susan Allport's book goes into the history of how omega-3s were discovered and what they'll mean for us in the future.

A controversial topic of the book is how omega-6 (king) and omega-3 (queen) compete for space in eicosanoid pathways. The omega-6s, the king, are the greater competitor and more inflammatory, while the omega-3, the queen, are a lesser competitor and less inflammatory.

She goes on about this relationship between omega-6 and omega-3 and gives examples from nature of how both the oils are found and used -- omega-3s in leaves (leaf fats), omega-6s in seeds (seed fats); omega-3s eaten more often in summer months, omega-6s in winter months by animals. The omega-6s are thought to bring on extra fat for warmth, for storage, for hibernation.

It's all pretty interesting stuff. And again, as I said, a bit controversial.

Now, in a new article, Susan gives a single-person account -- herself -- of results one gets from eating a high omega-6 diet for one month. I mean, we're not talking about a randomized, clinical trial. But nevertheless, her results are particularly interesting:

- reduced RMR
- omega-3 drop in blood (10% to 6%)
- omega-6 rise from 21% to 29%

- brachial artery dilation drop by 22%
- gain of 5 pounds

You can read more about her small experiment here. In the meantime, I'm popping my fish oil pills.

Low omega-6 to omega-3 ratio: Grain-fed meats or industrial vegetable oils?

Just a little note on the use of language. Clearly there is no such a thing as grain-fed or grass-fed beef, because one does not feed beef anything. One feeds cattle grain or grass, and then the resulting beef is said to be “grain-fed” or “grass-fed”. It is a manner of speaking that facilitates discourse, which is why it is used here.

To compensate for this digression, let me show you a graph, which pretty much summarizes the "punch line" of this post. The graph below shows the omega-6 fat contents of 1 lb (454 g) of grain-fed beef and 1 tablespoon (roughly 14 g) of a typical industrial vegetable oil (safflower oil). As you can see, there is a lot more omega-6 in the much smaller amount of industrial vegetable oil. A gram-for-gram comparison would practically make the beef content bar disappear.

It has been estimated that our Paleolithic ancestors consumed a diet with an omega-6 to omega-3 ratio of about 1. While other estimates exist, the general consensus seems to be that that ratio was not much greater than 5. Western diets, in contrast, typically have omega-6 to omega-3 ratios of between 15 and 40. In some cases, the ratio is even higher.

Omega-6 fats are essential fats, meaning that they must be part of one’s diet. Fats make up about 60 percent of our brain. About 20 percent is made up of omega-6 and omega-3 fats. The primary omega-6 fat found in our brain is arachidonic acid, which is either synthesized by our body based on linoleic acid from plant foods or obtained directly from animal foods such as meat and eggs. The predominant omega-3 fat found in our brain is docosahexaenoic acid (DHA), of which certain types of fish and algae are rich sources.

Inflammation is an important process in the human body, without which wounds would never heal. Incidentally, muscle gain would not occur without inflammation either. Strength training causes muscle damage and inflammation, after which recovery leads to muscle gain. Omega-6 fats play an important role in inflammation. Generally, they are pro-inflammatory.

Too much inflammation, particularly in a chronic fashion, is believed to be very detrimental to our health. A very high omega-6 to omega-3 ratio seems to cause excessive and chronic inflammation. The reason is that omega-3 fats are generally anti-inflammatory, counteracting the pro-inflammatory action of omega-6 fats. Over time, a very high omega-6 to omega-3 ratio is believed to cause a number of Western diseases. Among them are cardiovascular complications, cancer, and various autoimmune diseases.

So, should you worry about too much omega-6 from grain-fed meats?

If you think that the answer is “yes”, consider this. Apparently the (arguably) longest-living group in the world, the non-Westernized Okinawans, consume plenty of pork. Pork is a staple of their traditional diet. It is true that the average cut will have an omega-6 to omega-3 ratio of more than 7, which is not very favorable. Pork in general, whether grain-fed or not, is relatively high in omega-6 fats. As a side note, pork is not a good source of linoleic acid (found in plants), even though it is a rich source of arachidonic acid, the omega-6 fat synthesized from linoleic acid by various animals.

It is difficult to estimate the exact amounts of omega-6 and omega-3 fats from grain-fed cuts of meat; different sources provide different estimates. Here are some reasonable estimates based on various sources, including Nutritiondata.com. A typical 100 g portion of grain-fed pork should contain about 690 mg of omega-6 fats, and 120 mg of omega-3 fats. A typical 100 g portion of grain-fed beef should have about 234 mg of omega-6 fats, and 12 mg of omega-3 fats. It does not take that much omega-3 to counterbalance the omega-6 obtained from grain-fed pork or beef, even if one eats a lot of them. Two softgels of fish oil will normally contain about 720 mg of omega-3 fats (they will also come with 280 mg of omega-6 fats). Three sardines will have over 2 g of omega-3 fats, and less than 200 mg of omega-6 fats.

Industrial vegetable oils (made from, e.g., safflower seeds, soybean, and sunflower seeds) are very, very rich sources of omega-6 fats, in the form of linoleic acid. There is a lot more omega-6 in them than in grain-fed meats. One tablespoon of safflower oil contains over 10 g of omega-6 fats, in the form of linoleic acid, and virtually zero omega-3 fats. About 2 kg (4.4 lbs) of grain-fed pork, and 5 kg (11 lbs) of grain-fed beef will give you that much omega-6; but they will also come with omega-3.

How much fish oil does one need to neutralize 10 g of pure omega-6 fats? A lot! And there is a problem. Excessive fish oil consumption may be toxic to the liver.

If you cook with industrial vegetable oils rich in linoleic acid (this excludes olive and coconut oils), or eat out a lot in restaurants that use them (the vast majority), you will probably be consuming significantly more than 10 g of omega-6 fats per day. The likely negative health effects of eating grain-fed meats pales in comparison with the likely negative health effects of this much omega-6 fats from industrial vegetable oils.

You should reduce as much as possible your consumption of industrial vegetable oils rich in linoleic acid, as well as other products that use them (e.g., margarine). Keep in mind that industrial vegetable oils are in many, many industrialized foods; even canned sardines, if they are canned with soybean oil.

It is also advisable to couple this with moderate consumption of fish rich in omega-3, such as sardines and salmon. (See this post for a sardine recipe.) Taking large doses of fish oil every day may not be such a good idea.

Should you also consume only grass-fed meat? Do it if you can. But, if you cannot, maybe you shouldn’t worry too much about it. This also applies to eggs, dairy, and other animal products.

References:

Elliott, W.H., & Elliott, D.C. (2009). Biochemistry and molecular biology. New York: NY: Oxford University Press.

Ramsden, C.E., Faurot, K.R., Carrera-Bastos, P., Cordain, L., De Lorgeril, M., & Sperling (2009). Dietary fat quality and coronary heart disease prevention: A unified theory based on evolutionary, historical, global, and modern perspectives. Current Treatment Options in Cardiovascular Medicine, 11(4), 289-301.

Schmidt, M.A. (1997). Smart fats: How dietary fats and oils affect mental, physical and emotional intelligence. Berkeley, CA: North Atlantic Books.

More on the Harvard study on saturated versus polyunsaturated fats

This is a follow up on this post, which addressed the main argument put forth in a recent BBC article. The BBC article argued that people should replace saturated with polyunsaturated fats to reduce their risk of heart disease.

Let us take a look at the actual Harvard study itself (i.e., the study discussed in the BBC article). The Harvard study is linked here.

This post, by Stephan Guyenet, already pointed out several problems with the study. Stephan actually reviewed the studies used in the meta-analysis, and also some that were excluded in the meta-analysis and that he believes should have been included.

Here are a few other problems, in addition to the ones already pointed out by Stephan:

One thing that looks suspicious about this Harvard meta-analysis study is that they say that: “Statistical evidence for substantial between-study heterogeneity was not present (Q-statistic p = 0.13; I2 = 37%).”

A meta-analysis is a study that essentially summarizes, in a statistically sophisticated way, a bunch of other studies (the “sourced” studies). Too much between-study heterogeneity (i.e., widely disparate results among sourced studies) is undesirable, because it can bias the results.

The problem is similar to that of trying to summarize net worth figures (e.g., by calculating their average) in a middle class neighborhood that happens to have a few billionaires living in it. The heterogeneity in wealth may lead to a wildly overestimated average.

Now, we know that p values go down with sample size, and are usually high with small samples unless the effect measured by the statistic is very strong, regardless of the statistic used.

Well, with a sample of only 8 studies, their p value (associated with the Q statistic) is close to being significant at the 0.05 level!

If this sample of sourced studies were a little higher (say, 20), there would be significant between-study heterogeneity, which would call the meta-analysis into question. This is a big problem, since a good meta-analysis is expected to include a large number of studies (e.g., greater than 100), and this one included only 8 studies.

Moreover, to the best of my knowledge, the Q statistic is not very reliable when used with small samples, due to its low power as a test of heterogeneity. This makes the p value reported even more problematic.

Finally, the sourced study with the largest sample (n = 9,057; thus possibly the most credible), indicated as “Minnesota CS” on Figure 2 of the Harvard study, found increased risk of heart disease associated with increased consumption of polyunsaturated fats and reduced consumption of saturated fats.

Reference:

Mozaffarian, D., Micha, R., & Wallace, S. (2010). Effects on Coronary Heart Disease of Increasing Polyunsaturated Fat in Place of Saturated Fat: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS Med., 7(3): e1000252. doi: 10.1371/journal.pmed.1000252.

BBC article's advice: Replace saturated with polyunsaturated fats

The BBC article is here. It is based on meta-analysis of eight previous studies conducted by Harvard researchers, which the article states cover more than 13,000 people. The article also says that: “… [saturated] fats raise the levels of bad cholesterol that block the arteries to the heart.” They are of course referring to LDL cholesterol as the "bad cholesterol".

Sourcing bias is a notorious problem with meta-analyses (i.e., the choice of studies to use in a meta-analysis). Another problem is that you cannot tell what the studies sourced controlled for. Consider a study that compares health markers for smokers and non-smokers, where the smokers eat more saturated fat than the non-smokers. This study may confuse the effect of smoking with that of saturated fat consumption. To be reliable, the study must analyze the effect of saturated fat consumption, controlling for smoking habits.

There are other statistical issues to be considered in meta-analyses. For example, some of the sourced studies may take nonlinear relationships into consideration and others not. In multivariate analysis studies, nonlinearity may lead to significantly different results from those obtained through more conventional linear analyses.

Finally, reaching misleading results with sound statistical analyses is not that hard. As my age went from 1 to 20 years, my weight was strongly correlated with the price of gasoline. Yet, neither my weight caused the price of gasoline, nor the other way around. When you look at an individual study, not a meta-analysis, you can at least try to identify the possible sources of bias and mistakes.

Having said that, a solid refutation of the main argument in the article can be made from many angles. Here is a simple refutation based on what I would call the “HDL cholesterol angle”, with links to posts and various refereed publications:

- Increasing HDL cholesterol levels, especially beyond 60 mg/dl, dramatically decreases the risk of heart disease; and this is an almost universal effect in humans. This reduction in risk occurs even for people who suffer from diabetes and familial hypercholesterolemia. The latter is a genetic condition that is associated with very elevated LDL cholesterol and that is rare, typically afflicting 1 in 500 people in its heterozygous (and most common) form.

- Increasing consumption of saturated fats (present in: lard, fatty meat, coconut oil) and dietary cholesterol (from: fish, organ meats, eggs), while decreasing consumption of refined carbohydrates (e.g., pasta, white bread) and sugars (e.g., table sugar, high fructose corn syrup), significantly increases HDL cholesterol for the vast majority of people. Neither omega-6 nor omega-3 polyunsaturated fats lead to the same results. Omega-3 fats do reduce triglycerides, and increase HDL somewhat, but their effect on HDL pales in comparison with that of saturated fats. Excessive consumption of omega-6 fats is associated with chronic inflammation and related health problems.

- With the exception of cases involving familial hypercholesterolemia, there is no conclusive evidence that LDL cholesterol levels are associated with heart disease. Two widely used online calculators of risk of heart disease, based on the Framingham Heart Study and the Reynold Risk Score, do not even ask for LDL cholesterol levels to estimate risk. And that is not because they calculate LDL cholesterol based on other figures; they do not ask for VLDL cholesterol or triglycerides either.

After reading the BBC article again, it is clear that they are re-stating, in general terms, Rudolph Virchow’s mid-1800s lipid hypothesis. And they do so as if it was big news!

Steamed gulf shrimp with vegetables

Few would argue against eating seafood several times a week, except in the case of seafood allergy. Shrimp is a very good option, especially if it is not farm raised.

100 g of shrimp will typically have 20 g of protein, and about 152 mg of cholesterol (this is good for your health). It will also have about 0.6 g of omega-3 fats, and 0.03 g of omega-6; an omega-3 to omega-6 ratio of about 20.

My wife prepared this steamed gulf shrimp with vegetables dish. And it was very, very delicious. Here is her recipe:

- Add a small amount of olive oil and water to a frying pan.
- Add 1 lb of wild-caught peeled gulf shrimp, cabbage, onion, and asparagus (or green beans, as in the photo).
- Cook in low heat for 15 minutes.
- Add spinach and cook in low heat for another 10 minutes.
- Turn off heat, season to taste while mixing; I suggest using garlic powder, cumin powder, and parsley flakes.

Peeled shrimp is usually farm raised, which does not have the same amount of omega-3, or the same ratio of omega-3 to omega-6, as wild-caught shrimp. This small “salad” gulf shrimp was an exception.

Check the package. If it doesn’t explicitly say “wild”, you are better off buying wild-caught shrimp and peeling it yourself. Shrimp peelers are sold in most supermarkets; the one I use looks like a Velociraptor claw.

Eating fish whole: Sardines

Different parts of a fish have different types of nutrients that are important for our health; this includes bones and organs. Therefore it makes sense to consume the fish whole, not just filets made from it. This is easier to do with small than big fish.

Small fish have the added advantage that they have very low concentrations of metals, compared to large fish. The reason for this is that small fish are usually low in the food chain, typically feeding mostly on plankton, especially algae. Large carnivorous fish tend to accumulate metals in their body, and their consumption over time may lead to the accumulation of toxic levels of metals in our bodies.

One of my favorite types of small fish is the sardine. The photo below is of a dish of sardines and vegetables that I prepared recently. Another small fish favorite is the smelt (see this post). I buy wild-caught sardines regularly at the supermarket.

Sardines are very affordable, and typically available throughout the year. In fact, sardines usually sell for the lowest price among all fish in my supermarket; lower even than tilapia and catfish. I generally avoid tilapia and catfish because they are often farmed (tilapia, almost always), and have a poor omega-6 to omega-3 ratio. Sardines are rich in omega-3, which they obtain from algae. They have approximately 14 times more omega-3 than omega-6 fatty acids. This is an excellent ratio, enough to make up for the poorer ratio of some other foods consumed on a day.

This link gives a nutritional breakdown of canned sardines; possibly wild, since they are listed as Pacific sardines. (Fish listed as Atlantic are often farm-raised.) The wild sardines that I buy and eat probably have a higher vitamin and mineral content that the ones the link refers to, including higher calcium content, because they are not canned or processed in any way. Two sardines should amount to a little more than 100 g; of which about 1.6 g will be the omega-3 content. This is a pretty good amount of omega-3, second only to a few other fish, like wild-caught salmon.

Below is a simple recipe. I used it to prepare the sardines shown on the photo above.

- Steam cook the sardines for 1 hour.
- Spread the steam cooked sardines on a sheet pan covered with aluminum foil; use light olive oil to prevent the sardines from sticking to the foil.
- Preheat the oven to 350 degrees Fahrenheit.
- Season the steam cooked sardines to taste; I suggest using a small amount of salt, and some chili powder, garlic powder, cayenne pepper, and herbs.
- Bake the sardines for 30 minutes, turn the oven off, and leave them there for 1 hour.

The veggies on the plate are a mix of the following: sweet potato, carrot, celery, zucchini, asparagus, cabbage, and onion. I usually add spinach but I had none around today. They were cooked in a covered frying pan, with olive oil and a little bit of water, in low heat. The cabbage and onion pieces were added to the mix last, so that in the end they had the same consistency as the other veggies.

I do not clean, or gut, my sardines. Normally I just wash them in water, as they come from the supermarket, and immediately start cooking them. Also, I eat them whole, including the head and tail. Since they feed primarily on plant matter, and have a very small digestive tract, there is not much to be “cleaned” off of them anyway. In this sense, they are like smelts and other small fish.

For about a year now I have been eating them like that; and so have my family (wife and 4 kids), of their own volition. Other than some initial ew’s, nobody has ever had even a hint of a digestive problem as a result of eating the sardines like I do. Maybe the Kock family members share a common crocodile-like digestive system, but I think most people will do fine following the same approach. This is very likely the way most of our hominid ancestors ate small fish.

If you prepare the sardines as above, they will be ready to store, or eat somewhat cold. There are several variations of this recipe. For example, you can bake the sardines for 40 minutes, and then serve them hot.

You can also add the stored sardines later to a soup, lightly steam them in a frying pan (with a small amount of water), or sauté them for a meal. For the latter I would recommend using coconut oil and low heat. Butter can also be used, which will give the sardines a slightly different taste.

Go see your doctor, often

As I blog about health issues, and talk with people about them, I often notice that there is a growing contempt for the medical profession.

This comes in part from the fact that many MDs are still providing advice based on the mainstream assumption that saturated fat is the enemy. Much recent (and even some old) research suggests that among the main real enemies of good health are: chronic stress, refined carbs, refined sugars, industrial trans-fats, and an omega-6/omega-3 imbalance caused by consumption of industrial vegetable oils rich in omega-6 fats.

Because of this disconnect, some people stop seeing their doctors regularly; others avoid doctors completely. Many rely exclusively on Internet advice, from health-related blogs (like this) and other sources. In my opinion, this is a BIG mistake.

A good MD has something that no blogger who is not an MD (like me) can have. He or she has direct access to a much larger group of people, and to confidential information that can clarify things that would look mysterious to non-MDs. They cannot share that information with others, but they know.

For example, often I hear from people that they did this and that, in terms of diet a lifestyle, and that their lab tests were such and such. Later I find out that what they told me was partially, or completely, wrong. That is, they distorted the truth, maybe subconsciously.

I have never met an MD who completely ignored hard facts, such as results of lab tests and common health-related measurements. I have never met an MD who tried to force me to do anything either; although I have to admit that some tend to be a bit pushy.

I see a doctor who does not agree with me; e.g., he wanted me to take statins. No problem; that is the way I like it. If my doctor will agree 100% with all I say, do I need to see that doctor?

My doctor does not question lab results though, and maybe I am changing a bit the way he thinks. He wanted me to take statins, but once I told him that I wanted to try a few other things first, he said: no problem. When the results came, he had that look on this face - maybe u wuz royt eh!?

Many, many patients are under the mistaken assumption that they need to please their doctors. A subconscious assumption for most, no doubt. I guess this is part of human nature, but I don’t think it is helpful to doctors or patients.

Patients actually need to work together with their doctors, see them often, do their own research, ask questions, and do those things that lead to health improvements – ideally measurable ones.

Saturated fat intake not associated with heart disease – Dr. Cordain’s article

I would like to comment on a recent article co-authored by Dr. Loren Cordain, and published in the journal Current Treatment Options in Cardiovascular Medicine, in 2009. Dr. Cordain is probably the leading expert today on the diet of our Stone Age ancestors.

The importance of this article comes from the fact that in the past Dr. Cordain has argued that our Stone Age ancestors have not consumed large amounts of saturated fat, because of the relatively low percentage of fat in the flesh of wild animals. This led, according to Dr. Cordain, to an evolved body design that is not well adapted to the consumption of significant amounts of saturated fat.

Yet, many other researchers have argued that saturated fats are beneficial to our health, with ample empirical evidence to back up their statements. The researchers at the Weston A. Price Foundation have been particularly prominent voices in favor of saturate fats.

Now, this acknowledgement that saturated fats (or saturated fatty acids) are not detrimental to health, particularly heart health, was made with qualifications. And, Dr. Cordain is not the first author of the article. Page 293 of the article states that:

Replacement of SFAs, especially palmitate, with MUFAs may provide moderate cardiometabolic benefits, and is unlikely to do harm. However, SFA reduction does not appear to be the most important dietary modification for CHD risk reduction.

(Notes: SFA=saturated fatty acids=saturated fat, think greasy steak and egg yolk; MUFAs=monounsaturated fatty acids, think olive oil and lard; CHD=coronary heart disease.)

Palmitate refers to palmitic acid, of which meat, butter, eggs, and dark chocolate are all good sources. Even salmon is a good source of palmitic acid, although it is also an excellent source of DHA and EPA omega-3 fat acids. EPA is eicosapentaenoic acid, and DHA is docosahexaenoic acid; both of which are found in fish.

So, the caution in the statement above does not make much sense given the mounting evidence that palmitic acid (especially when consumed with a low carb. diet, in my view), may have cardio-protective effects.

Nevertheless, this is a major shift from Dr. Cordain’s previous position that saturated fats cannot be part of a healthy diet because they do not fit well with what we currently know about the diet of our Stone Age ancestors.

Maybe those ancestors ate a lot of saturated fat after all, and that consumption led to adaptations that make saturated fat consumption healthy; again, in my view, as long as it is not accompanied by high consumption of refined carbs. and sugars.

Saturated fat was probably the most readily available type of fat to those ancestors, a rich source of calories, and virtually impossible to avoid given the main component of those ancestors’ diet – meat.

Assessment: n-3 fatty acids and cognitive decline study

Purpose of study: Observe how plasma n-3 fatty acids affect risk of cognitive decline in older adults.

Research methodology: Prospective human observational cohort study

Description: Beydoun et al (1) analyzed plasma fatty acids in cholesteryl esters and phospholipids in 2,251 white women and men ages 50-65 from 1987 to 1989 in a community in Minneapolis, MN. In subsequent years 1990 to 1992 and 1996 to 1998, researchers administered cognitive tests on the subjects.

Measurements: Blood analysis was performed through collection of 12-hour fasting blood followed by identity of peaks through gas chromatography. Reliability coefficient for the testing ranged from 0.50 to 0.93 for cholesteryl esters and from 0.50 to 0.89 for phospholipids.

Cognitive assessments included tests for delayed word recall, psychomotor speed and verbal fluency. The researchers properly noted that almost all subjects had education of high school or above, which was important to assure group comparability. Ages 65 and older were excluded to as not skew measurements as were those showing signs of early mental decline.

Problems: Disadvantages of this study were chiefly the amount of confounding variables, which required control through backward elimination. Despite the control and reducing subjects from initial 4,000 to the 2,251, the large amount of subjects introduced many covariates. As appropriate Beydoun et al reported a type 1 error level of 0.10 that was validated through statistical analysis.

Results: Study’s findings suggested n-3 fatty acids “may have substantial benefits in reducing risk of cognitive decline in the area of verbal fluency,” but did not suggest any benefit for psychomotor speed or delayed word recall. Further, findings revealed warranted enrichment of n-3 fatty acids in the diet of those with increased oxidative stress from hypertensive and dyslipidemia.

Assessment: Despite noteworthy effort on behalf of Beydoun et al to control variables by reducing the study to a homogenous population and by eliminating many covariates, the other multivariates acting as potential confounders leads me to agree with the researchers themselves that randomized, controlled, cross-over trials are necessary to determine more meaningful data.

Reference: Beydoun MA, Kaufman JS, Satia JA, Rosamond W, Folsom AR. Plasma n-3 fatty acids and the risk of cognitive decline in older adults: the Atherosclerosis Risk in Communities Study. Am J Clin Nutr 2007;85:1103-11. Available at: http://www.ajcn.org/cgi/content/full/85/4/1103.