Clinical Trial Shows Fatty15 Supports Liver Health

August 18, 2024

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Double Blinded & Placebo Controlled: Part II

Last week, we announced a recently published clinical trial in The Journal of Nutrition led by the University of California San Diego, showing that fatty15 can effectively raise C15:0 levels and treat nutritional C15:0 deficiency. Continuing on with our 3-part series on the results from this clinical trial, this week we’ll talk about how fatty15 promotes liver health, which is a key step to reversing nutritional C15:0 deficiency syndrome (aka Cellular Fragility Syndrome).

Great! What is Cellular Fragility Syndrome, again?

C15:0 (pentadecanoic acid) is an essential and sturdy fatty acid that helps to strengthen our cell membranes and protect them against premature breakdown. Studies support that if our cell membranes have C15:0 levels less than 0.2% of total fatty acids (or 5 µg/ml), they can become fragile, resulting in accelerated cellular aging and affected metabolic, heart, and liver health. As recently published in Metabolites, this C15:0 deficiency syndrome is called Cellular Fragility Syndrome.

How was liver health assessed in this clinical trial?

Chances are, when you get a blood test taken at your doctor’s office, they include a liver enzyme panel. This panel is used to assess healthy liver function and typically includes the following three liver enzymes:

Gamma-glutamyl transferase (GGT)
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)

If these liver enzyme levels are elevated, it can indicate that your liver is not functioning as well as it should. Findings of less-than-optimal liver function have become increasingly common since the 1980s.

The recent randomized, double blinded, and placebo controlled clinical trial was led by Dr. Jeffrey Schwimmer, who is a global leader in children’s liver health. In addition to showing that fatty15 supplementation raised C15:0 levels, he also measured and compared GGT, AST, and ALT levels in study participants (18-to-24-year-olds who had suboptimal liver function) at baseline and at 12 weeks.

What did this clinical trial find with regard to liver health?

Wonderfully, Dr. Schwimmer’s clinical trial found that fatty15 improved liver function within 12 weeks. Specifically:

Fatty15 effectively lowered GGT.
Study participants who took fatty15 and achieved C15:0 blood levels greater than 5 µg/ml (aka were not C15:0 deficient) also had significant reductions in ALT and AST.

These liver health benefits were seen among people who 1) took fatty15, and 2) achieved the “I-am-not-C15:0-deficient” levels (referred to as the “Threshold Group”). These results are summarized in the graph below. Importantly, these benefits were not observed in the placebo control group.

What does liver health have to do with Cellular Fragility Syndrome (aka nutritional C15:0 deficiency)?

Good question! As described in the journal Metabolites, here’s a play-by-play rundown on how Cellular Fragility Syndrome affects liver function:

When C15:0 levels in our cell membranes are low, our cells can become fragile, resulting in increased lipid peroxidation. This includes fragile red blood cells.
As part of our body’s specialized cleanup crew, cells in our liver (called Kupffer cells) engulf fragile red blood cells. If we have a lot of fragile red blood cells, this results in a buildup of red blood cell junk and free iron in our liver.
When this free iron builds up in our liver and combines with lipid peroxidation, this can cause a cellular issue called ferroptosis, all of which negatively affect liver function.

Importantly, this latest clinical trial showed that, by using fatty15 supplementation to raise C15:0 levels, this also resulted in improved liver function. Now we’re talking.

Culminating support of fatty15 as essential to supporting liver health

Remember how we mentioned that suboptimal liver function has become increasingly common since the 1980s? Well, that trend started around the same time that nutritional guidelines started doubling down on drastically reducing our intake of all dietary saturated fats – including whole fat cow’s milk and butter.

While these foods do have high levels of pro-inflammatory even-chain saturated fatty acids (like C16:0) that continue to be associated with a higher risk of type 2 diabetes, heart disease, and fatty liver disease, they are also our primary dietary source of healthy and essential C15:0. A leading hypothesis is that population-wide nutritional C15:0 deficiencies are a key driver for the rise in suboptimal liver function. This latest clinical trial supports this hypothesis.

Beyond this clinical trial, there have been many other peer-reviewed studies demonstrating the role of C15:0 in protecting our livers, including the following:

As shown in Kratz et al. and Sawh et al., both adults and children with higher C15:0 levels have better long-term liver health.
In relevant models of liver health described in Yoo et al., Wei et al. and Venn-Watson et al., pure C15:0 supplementation directly lowers liver lipid peroxidation, ALT, and AST – as well as protects the health of liver cells.
We also showed that fatty15 activates key receptors, called PPARɑ and PPARδ, which are known to be liver-protective mechanisms.
A previously published clinical trial by Chooi et al. that included adult women in Singapore showed that daily C15:0 supplementation for 12 weeks led to the healthiest livers, as well as healthier LDL cholesterol levels.

The take home point: double blinded and controlled clinical trials show that fatty15 promotes liver health, and that’s a darn good thing. Next week, in the last part of this 3-part series, we’ll cover what the latest clinical trial demonstrated in the way of protecting red blood cell health and treating Cellular Fragility Syndrome.* In the meantime, have a great week, everyone!