Understanding Fatty Acids and Health

tldr; Is understanding all the fatty acids and their interactions necessary for good health?

One of my X correspondents posed this excellent question:

Source

(For the answer to the second question, see the thread.)

My short answer on X was:

“1. Ultimately it's a black-box analysis. You don't need to understand what's happening with all the fatty acids. Just that differences from 'natural' cause disease.”

That’s true so far as it goes, but I thought that a little expansion might help people understand why I think that.

Dolphins Get Diabetes

How on Earth can dolphins get diabetes?

“Dolphins as Animal Models for Type 2 Diabetes: Sustained, Post-Prandial Hyperglycemia and Hyperinsulinemia” (Venn-Watson, 2011)

They don’t eat any carbohydrates, of course, as they live in the ocean and whatever tiny amount they get would be in the form of glucose or glycogen in their prey animals.

They also don’t eat any seed oils, at least not that I am aware of. In captivity, they are still fed fish, not some horrible biscuit concoction like many other zoo animals.

“Similar to humans, bottlenose dolphins (Tursiops truncatus) can develop metabolic syndrome and associated high ferritin…. (Venn-Watson, 2015)

These dolphins were under the care of the U.S. Navy, and were a generally healthy population, with longer life-spans, lower per-annum mortality, and “had consistently lower levels of stress hormones”.

“They are fed high-quality, frozen-thawed whole fish diets consisting of primarily capelin (Mallotus villosus), as well as herring (Clupea harengus), mackerel (Scomber japonicus), and/or squid (Loligo opalescens).” (Venn-Watson, 2015)

However, they had higher insulin, ferritin, and triglycerides than the wild population they were compared to.

Ferritin is Not a Marker of Iron Status

“Ferritin is the true measure of iron in blood, and high blood ferritin is reflected in iron overload. In humans, the severity of insulin resistance is associated with increasing serum ferritin levels and hemochromatosis…” (Venn-Watson, 2011)

“It is unknown precisely why ferritin increases in some people and how high ferritin increases the risk of metabolic syndrome [17–19].” (Venn-Watson, 2015)

This is, unfortunately, a common misconception. I discussed ferritin and iron in this post:

In a nutshell, ferritin is more of a marker of inflammation than of iron status. Ferritin is a protein used for iron transport and storage. But the test for ferritin is positive even if the protein contains no iron. So high ferritin reflects an inflammatory state and, one suspects, higher necrosis; and not higher iron intake or stores (Kell, 2014). Low ferritin can also reflect a low-inflammation state, as induced by athletic training, for instance.

So ferritin is a marker, a result of disease; not a mediator:

“2. (Science: chemistry) A chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle…”

No Dietary Carbohydrate, So What To Test?

“Fish are high in essential Ω-3 polyunsaturated fatty acids, and these nutrients have been associated with both beneficial and detrimental effects related to diabetes [7–9].” (Venn-Watson, 2015)

So they take blood from both the domestic and wild dolphins (after checking to make sure the wild dolphins have full stomachs, to see if there are any differences or correlations in their blood fatty acids and the fish in their diets.

“To assess potential protective factors against metabolic syndrome related to fish diets, fatty acids were compared between two dolphin populations with higher (n = 30, Group A) and lower (n = 19, Group B) mean insulin (11 ± 12 and 2 ± 5 μIU/ml, respectively; P < 0.0001) and their dietary fish.” (Venn-Watson, 2015)

And it turns out that the difference was in three fatty acids, due to the different, limited types of fish fed to the domestic dolphins.

‘Fixing’ Diet Resolved Malnutrition

Correcting their diets led to an increase in what they concluded was the causative fat, C:17.0, heptadecanoic acid; an odd-chain (odd number of carbons) saturated fat.

Figure 3 A. (Venn-Watson, 2015)

Normalizing dietary fatty acids resolved diabetes.

And for Dr. Krongrad’s question, while these researchers did a good bit of analysis to determine what was happening, simply returning the dolphins to a natural diet would have had the same effect.

Something like this:

“Marked Improvement in Carbohydrate and Lipid Metabolism in Diabetic Australian Aborigines After Temporary Reversion to Traditional Lifestyle.” (O’Dea, 1984)

Or this:

“Circulating Biomarkers of Dairy Fat and Risk of Incident Diabetes Mellitus Among Men and Women in the United States in Two Large Prospective Cohorts” (Yakoob, 2016)

“In 2 prospective cohorts, higher plasma dairy fatty acid concentrations were associated with lower incident diabetes mellitus.” (Yakoob, 2016)

It turns out that heptadecanoic acid is a fat in full-fat dairy, and is used as a marker of dairy consumption.

“C17:0, also called margaric or heptadecanoic acid, is a saturated fatty acid present in bovine milk fat and was the original component of margarine (hence, margarine’s name) in the late 1800s [32,33]. C17:0 in margarine, however, was replaced with less costly and more readily available plant-based and trans-fatty acids [32]. When off the shelf dairy products were tested in the current study, C17:0 was highest in butter and whole fat yogurt and not detectable in nonfat dairy products. Butter had 10-fold higher levels of C17:0 compared to the next highest C17:0 foods. Interestingly, despite widespread recommendations for consumers to avoid high fat foods (including whole fat dairy products), previous studies in humans have demonstrated that whole fat dairy consumption is associated with multiple health benefits, including lower risks of insulin resistance, metabolic syndrome, and type 2 diabetes [34–38].” (Venn-Watson, 2015)

So while we are often told that saturated fats cause diabetes, in fact we have ample evidence that they are in fact protective. The change in the human diet suggests that the lack of these beneficial fats may be part of the mechanism of our increase in chronic disease.

Cheetahs Get Chronic Disease

Captive cheetahs, like humans living in a non-‘wild’ condition, suffer from a variety of chronic diseases. Despite improvements in conditions,

“…they still suffer from a range of unusual diseases not typically seen in other large captive felids. These include glomerulosclerosis [1–4], renal amyloidosis [4], lympho-plasmacytic gastritis [2,5,6], veno-occlusive disease [2,7], splenic myelolipomas, cardiac fibrosis [2,4], adrenal cortical hyperplasia [1,2,4,8] with lymphocytic depletion of the spleen [2], pancreatic atrophy [2] as well as several ill-defined disorders of the neurological system [2,9].” (Tordiffe, 2016)

Some of these sound similar to human diseases, “veno-occlusive disease” is in fact a human disease. And, like humans:

“Some of these chronic degenerative diseases eventually affect the majority of cheetahs in captivity and are considered to be the primary cause of morbidity and mortality in adult animals [2,10].” (Tordiffe, 2016)

And the similarity extends even further.

“In contrast, the incidence of similar conditions in free-ranging cheetahs was found to be very low [10,11].” (Tordiffe, 2016)

Just as human hunter-gatherers have exceedingly low levels of chronic disease.

“Although low heterozygosity and the stress of captivity have been suggested as causal factors [8,12], recent studies have started to focus on the contribution of potential dietary factors in the pathogenesis of these diseases [13-15].” (Tordiffe, 2016)

In animals and humans, ‘stress’ is over-credited with being a cause of disease. Wild animals or humans will always have a higher-stress life, as food shortages and violent death are much more common, and lives are generally shorter.

Yet they are healthier. So back to diet.

Diet Has a Dramatic Impact on Fats

As with the dolphins (Tordiffe’s reference 56 is (Venn-Watson, 2015)), these researchers look into the role of fatty acids. Like dolphins, cheetahs are obligate carnivores. These researchers, reviewing the effect of heptadecanoic acid, observe, “It is, nevertheless, interesting that this SFA, presumed to be non-essential in the diet, had such a dramatic metabolic effect in another obligatory carnivore.”

The captive cheetahs “were fed a diet consisting mostly of muscle meat from eviscerated and exsanguinated donkeys, supplemented with a multivitamin and mineral powder (Predator Powder 1, Healthtech, South Africa).” One assumes these donkeys were domesticated, and likely fed a high-grain diet typical of that fed to domestic herbivores. The wild cheetahs, like the wild dolphins, ate what they caught.

“All of the individual serum MUFAs and PUFAs as well as the total MUFA and PUFA concentrations differed between the free-ranging and captive cheetahs (p < 0.0005), with free-ranging cheetahs having lower values for most FAs….

“Free-ranging cheetahs also had lower total FA concentrations than the captive cheetahs (p = 0.001), whereas total SFA concentrations did not differ. Both the SFA:PUFA and SFA:MUFA ratios were on average more than three-fold higher in free-ranging cheetahs than in captive cheetahs (p < 0.0005).”

Cats are obviously very different from humans, as are dolphins. But there are similarities in fatty acid metabolism that transcend species, as we discussed with Prof. Hulbert.

“As predicted, both the SFA:PUFA and SFA:MUFA ratios were significantly higher in the free-ranging animals.” (Tordiffe, 2016)

What’s surprising here is that the biggest goal of human dietary guidelines is to decrease the SFA:PUFA ratio. This has been the primary recommendation of the American Heart Association since 1961, for instance.

“Substitution of poly-unsaturated for a substantial part of the saturated fat in the diet may also be a valuable addition to this program.” (Page, 1961)

As with cheetahs, an increasing PUFA:SFA ratio has been associated with higher levels of a variety of chronic diseases.

“The differences in serum PUFA concentrations between free-ranging and captive cheetahs are also consistent with our hypothesis, because these unsaturated FAs occur at lower serum concentrations in the free-ranging than in captive cheetahs, primarily due to lower dietary intake.” (Tordiffe, 2016)

And, perhaps most surprising:

“Arachidonic acid was the only PUFA for which concentrations were higher in the free-ranging cheetahs. This again may reflect differences in dietary intake, as AA makes up a larger proportion (7.63% to 9.3%) of the intramuscular FAs in wild game species such as the springbok (Antidorcas marsupialis) [49] than in donkey muscle meat (1.65% to 2.09%) [36].” (Tordiffe, 2016)

It is often claimed by those advocating for a high intake of seed oils that the absence of higher levels of AA is evidence of benefit. Yet here it is the cheetahs with higher AA from eating meat that are healthier.

And, as with the dolphins and the healthier humans:

“Heptadecanoic acid, also known as margaric acid, is a SFA with an uneven number of carbon atoms and is normally found at low concentrations in the adipose tissue and milk fat of ruminants. The mean serum concentration of this SFA was higher in free-ranging compared to captive cheetahs.” (Tordiffe, 2016)

Sadly, not having the resources of the U.S. Navy at their disposal, these researchers were not able to do a dietary trial for these animals to see if fixing their malnutrition would improve their chronic diseases.

Conclusion

“How can anyone even understand fatty acids given all the natural (and synthetic) interconversions?”—Dr. Arnon Krongard

So while the answer may we be “we can’t”, it doesn’t seem to be necessary.

Simply returning to a pattern of fat consumption similar to that consumed in a natural, wild environment may be sufficient to maintain or restore health.

What’s surprising about these two studies is that they suggest that a sufficiency of saturated fats is important in the diet.

Which suggests they should be considered essential (Venn-Watson, 2020).

---

References

Kell, D. B., & Pretorius, E. (2014). Serum Ferritin Is an Important Inflammatory Disease Marker, as It Is Mainly a Leakage Product from Damaged Cells. Metallomics: Integrated Biometal Science, 6(4), 748–773. https://doi.org/10.1039/c3mt00347g

O’Dea, K. (1984). Marked Improvement in Carbohydrate and Lipid Metabolism in Diabetic Australian Aborigines After Temporary Reversion to Traditional Lifestyle. Diabetes, 33(6), 596–603. https://doi.org/10.2337/diab.33.6.596

Page, I. H., Allen, E. V., Chamberlain, F. L., Keys, A., Stamler, J., & Stare, F. J. (1961). Dietary Fat and Its Relation to Heart Attacks and Strokes. Circulation, 23(1), 133–136. https://doi.org/10.1161/01.CIR.23.1.133

Tordiffe, A. S. W., Wachter, B., Heinrich, S. K., Reyers, F., & Mienie, L. J. (2016). Comparative Serum Fatty Acid Profiles of Captive and Free-Ranging Cheetahs (Acinonyx jubatus) in Namibia. PLOS ONE, 11(12), e0167608. https://doi.org/10.1371/journal.pone.0167608

Venn-Watson, S., Carlin, K., & Ridgway, S. (2011). Dolphins as Animal Models for Type 2 Diabetes: Sustained, Post-Prandial Hyperglycemia and Hyperinsulinemia. General and Comparative Endocrinology, 170(1), 193–199. https://doi.org/10.1016/j.ygcen.2010.10.005

Venn-Watson, S. K., Parry, C., Baird, M., Stevenson, S., Carlin, K., Daniels, R., Smith, C. R., Jones, R., Wells, R. S., Ridgway, S., & Jensen, E. D. (2015). Increased Dietary Intake of Saturated Fatty Acid Heptadecanoic Acid (C17:0) Associated with Decreasing Ferritin and Alleviated Metabolic Syndrome in Dolphins. PLOS ONE, 10(7), e0132117. https://doi.org/10.1371/journal.pone.0132117

Venn-Watson, S., Lumpkin, R., & Dennis, E. A. (2020). Efficacy of Dietary Odd-Chain Saturated Fatty Acid Pentadecanoic Acid Parallels Broad Associated Health Benefits in Humans: Could It Be Essential? Scientific Reports, 10(1), Article 1. https://doi.org/10.1038/s41598-020-64960-y

Yakoob, M. Y., Shi, P., Willett, W. C., Rexrode, K. M., Campos, H., Orav, E. J., Hu, F. B., & Mozaffarian, D. (2016). Circulating Biomarkers of Dairy Fat and Risk of Incident Diabetes Mellitus Among Men and Women in the United States in Two Large Prospective Cohorts. Circulation, 133(17), 1645–1654. https://doi.org/10.1161/CIRCULATIONAHA.115.018410