What exactly makes an essential fatty acid, essential?

Healthy Aging

How Essential Fatty Acids Are Discovered

The countdown is on until Simon & Schuster’s March 25th release of The Longevity Nutrient. This book tracks our 20-year scientific journey – starting with an unexpected discovery of C15:0’s health benefits while helping dolphins – which has culminated in a movement to improve global health. And dare we say, humanity?

In this series of Science Says!, we provide a behind-the-scenes science peek relevant to each of the book’s chapters – from surprising dolphin discoveries to longevity molecule must-haves, from how essential fatty acids are discovered to the many ways C15:0 works, from how a newly found nutritional deficiency accelerates aging to how fixing and optimizing our C15:0 levels can slow aging to help us live healthier, longer.

This week, let’s talk about how essential fatty acids are discovered. We’re going old school, folks… before getting us caught up to modern times.

So, what makes an essential fatty acid, essential?

You have heard us talk about C15:0 as the first essential fatty acid to be discovered in over 90 years. Which is pretty exciting. But how does one go about determining if a nutrient is truly essential?

Well, as described by Holman back in 1958, an essential fatty acid must meet the following criteria:

1. It is a nutrient required by our body to maintain our baseline physiological health.
2. Our body doesn’t make enough of this nutrient on its own to support healthy levels.
3. Without enough of this nutrient in our diet or supplements, we develop a deficiency syndrome.

Today, only three nutrients meet the criteria of an essential fatty acid: linoleic acid (LA, an omega-6 fatty acid), alpha linolenic acid (ALA, an omega-3 fatty acid), and – as we first published in Nature’s Scientific Reports – C15:0 (pentadecanoic acid, an odd-chain saturated fatty acid).

Got it. How were the omegas discovered as essential fatty acids?

While The Longevity Nutrient shares the full interesting history behind how LA and ALA were discovered as essential, here are the some of the key points:

• During 1929-1931, Dr. George and Mildred Burr found that baby mice deprived of milkfat (but still nourished with vitamins A though E) had poor body growth and poor hair, skin, and kidney health, indicative of a nutritional deficiency.
• At the time, this was mind-blowing. Simply because everyone thought that fat had no health benefits (beyond providing calories, that is).
• Over a series of studies, they narrowed the known fatty acids in milkfat down to those which were essential to keeping good body growth and healthy hair, skin and kidneys in baby mice. Namely, LA and ALA. While they initially umbrellaed these nutrients as “Vitamin F”, they were renamed as Essential Fatty Acids.

While ALA and LA meet the criteria of essential fatty acids, clinically relevant deficiencies in these fatty acids in humans are actually quite rare. This is because both fatty acids are readily available in lots of foods. In fact, having too high levels of omega-6 fatty acids, including LA, can result in a pro-inflammatory state.

In contrast, our bodies use ALA to make the better known omega-3s, EPA and DHA. While EPA and DHA are not technically essential fatty acids, they can offer a myriad of health benefits, especially when not oxidized.

Okay, how does C15:0 meet the criteria of an essential fatty acid?

It took 90 years, but as we have shared, aging dolphins initially helped to reveal that C15:0 is essential to maintaining our physiological health. That story is, well, in the book. Fast forward 10 years since that initial discovery, and we now know the following:

• C15:0 has many beneficial activities. C15:0 is a sturdy fatty acid with numerous cell-based benefits, including strengthening cell membranes, repairing mitochondria, activating AMPK, AKT, and PPARs, and inhibiting mTOR, JAK-STAT, and HDAC-6.
• Critical C15:0 levels are needed. Our cell membranes require > 0.2% (20 uM, or 5 ug/ml) of C15:0 to maintain adequate strength and to protect overall cellular health.
• We need C15:0 from our diet. Our body doesn’t make enough C15:0 on its own to reliably support these healthy levels.
• Low C15:0 results in a nutritional deficiency syndrome. As described in Metabolites, without enough added C15:0 in our diet or supplements (approximately 100 to 200 mg/day), we can develop a deficiency syndrome called Cellular Fragility Syndrome, which causes ferroptosis, a new form of cell death that accelerates aging and impairs our metabolic, heart, liver, and red blood cell health.
• C15:0 is needed for healthy growth. Repeating the rodent studies from Dr. George and Mildred Burr, mom and baby rats deficient in C15:0 develop nutritional deficiencies, which are alleviated with added C15:0 in their diets. This is holding true in human epidemiological studies, too. George et al. and Li et al. showed that human moms with higher C15:0 result in babies with higher C15:0… and better body growth and cognitive development.
• C15:0’s essentiality has been validated multiple times. Four independent teams in the U.S., Canada, China, and France have each validated C15:0 as an essential fatty acid.

Unlike the other essential fatty acids, C15:0 nutritional deficiencies appear to be common – affecting as many as 1 in 3 people globally. Which may explain why metabolic, heart, and liver health have been declining in younger and younger people. But that story has its own chapter in The Longevity Nutrient (Chapter 9, The Nutritional C15:0 Deficiency Fallout: Broken Generations).

In summary, C15:0 has indeed emerged as an essential fatty acid. Thank you, dolphins.