Are Saturated Fats Good or Bad? A Focus on C15:0 versus C16:0

With the upcoming release of USDA’s 2026-2030 Dietary Guidelines for Americans, the topic of saturated fats is gaining extra attention these days. 

It seems that for every study showing that saturated fats are bad for us, there is another saying that they are not bad…and others even showing that some are good. Which leaves a lot of us confused and asking the question, “Are dietary saturated fats good, bad, or neutral for us?” Alas, the answer is, “Yes.”

So, let’s review the latest science supporting how saturated fats, based on the food source and the type of saturated fat, can influence our health in very different ways. And how C15:0, an odd-chain saturated fatty acid, is meeting the criteria of a nutrient that can help ensure healthy aging for all.

Well, not all saturated fats are created equally.

First, it’s good to know there are two distinct types of saturated fats: even-chain and odd-chain saturated fatty acids. Given repeated findings across numerous prospective cohort meta-analyses, paired with experimental studies and randomized controlled clinical trials, it has become indisputable that while some saturated fats can be harmful, others are emerging as nutrients that are essential to maintaining our long-term health. 

As their names suggest:

Even-chain saturated fats have an even number of carbons, such as C16:0 (aka, palmitic acid). 

• C16:0 and its metabolites directly activate pro-inflammatory pathways, like NF-kB, TNFɑ and IL-6
• C16:0 induces mitochondrial dysfunction
• C16:0 is routinely used in preclinical models to induce inflammation, insulin resistance and fatty liver disease
• In prospective cohort studies following large populations over years, higher levels of even-chain saturated fatty acids, including C16:0, have been repeatedly associated with a higher risk of developing type 2 diabetes  and cardiovascular disease.
• In a cross-over clinical trial with high dairy fat diets, increased C16:0 levels were associated with increased blood pressure.

In contrast, odd-chain saturated fats have an odd number of carbons, such as C15:0 (aka, pentadecanoic acid).

• C15:0 directly inhibits pro-inflammatory pathways, including JAK-STAT and NF-kB
• C15:0 directly activates glucose control mechanisms, including AMPK and AKT
• C15:0 supports mitochondrial function
• In preclinical models, C15:0 protects healthy immune responses as well as metabolic, cardiovascular, liver and gut health 
• In prospective cohort meta-analyses following large populations over years, higher levels of odd-chain saturated fatty acids, including C15:0, have been repeatedly associated with better protected long-term metabolic and heart health
• Randomized clinical trials have shown that people who supplemented with C15:0 and had raised C15:0 levels had better protected liver, red blood cell, cardiovascular biomarker, and gut microbiome health.
• In a cross-over clinical trial with high dairy fat diets, increased C15:0 levels were associated with improved vascular function

These studies prove that, while some even-chain saturated fatty acids (especially C16:0) can have negative effects, odd-chain saturated fatty acids (especially C15:0) can be beneficial. Which brings us to the question, which foods have C15:0 versus C16:0?

Dairy fat is our primary dietary source of good C15:0. But it also has C16:0.

Our most common dietary source of C15:0 is - by far - dairy fat. Wholefat dairy products are such a reliable source of C15:0, that this hidden good fat has long been used by scientists as a biomarker of how much dairy fat one eats. While C15:0 is also present in red meat and some types of fish, dairy fat remains the most reliable determinant of our C15:0 levels. The more whole fat dairy we eat, the higher our C15:0 levels.

Alas, dairy fat contains both even- and odd-chain saturated fatty acids. While milkfat typically contains only about 1% of C15:0, it has around 30% of C16:0. Scientists have proposed that the opposing effects of even vs. odd-chain saturated fatty acids could explain why the outcomes of studies on dairy fats are so varied. And how the net effects are sometimes neutral - the negative effects of bad fats may be canceling out the positive effects of the good ones.

As further evidence, preclinical models have shown that C15:0 has insulin-sensitizing, immune calming, and liver protective effects; C17:0 has mild immune calming effects. In contrast, these same animal models fed whole dairy fat had increased inflammation and impaired liver function. Further, these studies showed that C16:0 is proinflammatory and impairs glucose response. Due to these findings, scientists concluded that dairy fat can sometimes have a net negative effect because of the relatively higher amounts of C16:0 compared to C15:0 and C17:0.

When looking at human studies, a cross-over clinical trial with healthy adults showed that people who ate more daily servings of whole fat dairy products had higher C15:0, which was associated with improved vascular function. Which is great. However, eating more dairy fat also resulted in higher C16:0, which was associated with higher blood pressure. The authors’ conclusion of their study? Different saturated fatty acids in dairy fat can have different and opposing effects.

A recent massive meta-analysis including 27 prospective cohort studies from the U.S., Europe, Asia, and Australia followed over 100,000 people for many years to evaluate dose-response associations between different fatty acids and the likelihood of protecting long-term metabolic health. This study showed that - among all fatty acids evaluated - higher levels of odd-chain saturated fatty acids, including C15:0, were the strongest predictors of long-term metabolic health. Specifically, every 0.1% increase in C15:0 levels translated to a 32% reduced risk of developing impaired metabolic function.

In summary, the opposite effects of odd- vs. even-chain saturated fatty acid help explain why studies that simply lump “saturated fats”into a single category have been so varied and unreliable in their results.

With the data we now have available across 100+ peer-reviewed studies, future research and dietary recommendations related to saturated fats need to responsibly differentiate between the types of saturated fats, especially C15:0 versus C16:0.

The type of dairy fat we eat matters.

To make things even more complicated, not all whole dairy fat has the same amount of C15:0. For example, dairy fat from grass-fed cows has 26% more C15:0 compared to dairy fat from corn-fed animals. Further, cheese (including cheese from grass-fed sheep, like pecorino) can have some of the highest levels of C15:0. A prospective cohort study demonstrated that higher amounts of dietary cheese were associated with higher C15:0 levels compared to other dairy products. These higher C15:0 levels from cheese have been associated with better cognitive development in children. Cheese as a healthy source of C15:0 is further supported by a recently published, extensive 25-year prospective cohort study which showed that adults who ate more high fat dairy products, specifically cheese and cream, had better protected long-term cognitive health. These studies support that cheese from grass-fed animals may be an optimal dietary source of C15:0. 

50-year-old recommendations to decrease all saturated fats haven’t improved our health. In fact, our overall health has gotten worse.

In 1977, Congress released Dietary Guidelines for Americans, which heavily emphasized the reduction of all dietary saturated fats, especially by lowering our intake of whole dairy fat products. These guidelines were not only intended to lower LDL cholesterol among men, who were dying at high rates from heart disease, but they were also supposed to help stem the rise in type 2 diabetes and obesity in the general population. In 1980, approximately 3% to 3.6% of Americans had diabetes and 15% had obesity. It was believed that decreasing our intake of saturated fats would help reverse these trends.

Since the 1977 Guidelines were released, however, we haven’t gotten healthier as a nation on these fronts. Instead, we’ve gotten sicker. Today, about 10% of Americans (35 million people)  have type 2 diabetes and 40% have obesity. It should seem clear that these guidelines have not helped to decrease type 2 diabetes and obesity. 

It is also important to note that the guidelines to reduce saturated fat intake have been based on science demonstrating that saturated fats raise LDL cholesterol and therefore the risk of cardiovascular disease. In contrast, C15:0 has been shown both in preclinical studies and controlled clinical trials to lower LDL cholesterol. This difference is important, given the projections that the prevalence of cardiovascular diseases is expected to increase over the next 30 years.

Given the prospective cohort meta-analyses shared above, there is a need to better understand if reducing dietary odd-chain saturated fatty acids, including C15:0, have actually contributed to the rise in cardiometabolic conditions.

Evidence of nutritional C15:0 deficiencies.

The USDA Dietary Guidelines for Americans’ recommendation to limit all saturated fats has resulted in increasing avoidance of cow’s milk altogether. Each new generation of Americans is more likely to avoid cow’s milk, which has alarmed even the USDA. In their summary, the USDA concludes that this trend is proving difficult to reverse.

Reduced dairy fat intake has resulted in lower populationwide C15:0 levels, and as described above, these lower levels are coinciding with increased incidence of cardiometabolic conditions. Beyond association, the detailed pathophysiology of a nutritional C15:0 deficiency syndrome, called Cellular Fragility Syndrome, has been described. 

This pathophysiology was initially revealed by studies helping to continually improve the health of older Navy dolphins. In these studies, it was found that about 1 in 3 older dolphins were developing a cluster of conditions, including  insulin resistance, chronic inflammation, hyperlipidemia, anemia, iron overload, and fatty liver disease. The primary driver for these conditions was low dietary C15:0, and when C15:0 levels were restored, components of this deficiency syndrome were reversed. Since those original studies, the ability for C15:0 supplementation to reverse all components of Cellular Fragility Syndrome has been demonstrated in multiple preclinical models and independent teams.

Here’s how low C15:0 levels can cause Cellular Fragility Syndrome:

• C15:0 is a stable fatty acid that strengthens cell membranes against breakdown. Specifically, by protecting against lipid peroxidation. 
• Low C15:0 levels can make cells more fragile, including red blood cells. In bloodwork, this may be first seen with decreasing hemoglobin and increasing red blood cell distribution width (RDW).
• These fragile red blood cells are engulfed by macrophages in the liver, called Kupffer cells. Over time, this results in too much iron in the liver.  This can be seen in bloodwork as hyperferritinemia.
• The combined effects of weakened cell membranes, lipid peroxidation, and excess intracellular iron results in ferroptosis, a new form of cell death discovered by scientists at Columbia University.
• In turn, ferroptosis accelerates aging and impairs metabolic, liver, immune, cardiovascular, and cognitive function.

While there have been over 20,000 peer-reviewed papers on ferroptosis, it has not been clear why this new form of cell death emerged in the first place.  An emerging hypothesis is that nutritional C15:0 deficiencies, caused by limiting our intake of all dietary saturated fats, may be a primary driver for ferroptosis.

Evidence of C15:0 as an essential nutrient.

By definition, a nutrient is a substance that provides nourishment essential for growth and the maintenance of life. By helping to ensure that we 1) have healthy growth and development and 2) maintain long-term health, nutrients support healthy aging throughout our lives.

A consortium of nutrition experts developed a list of evidence-based criteria for nutrients. As you can see below, the evidence supporting C15:0 as a core nutrient has been rapidly growing over the past decade: 

• Prospective cohort studies. Meta-analyses (studies of multiple prospective studies) tracking tens of thousands of people over many years repeatedly show that people with higher C15:0 are associated with better protected long-term cardiovascular and metabolic health.
• Randomized clinical trials. Across six randomized and controlled clinical trials, higher C15:0 intake has been shown to increase C15:0 levels, and these higher C15:0 levels have been associated with protected red blood cell, liver, cholesterol, gut microbiome, and vascular health.
• Case-control studies. Similarly, numerous case-control studies with pre-clinical models repeatedly show that C15:0 supplementation supports cholesterol, immune, red blood cell, liver, glucose, and gut health better than non-C15:0 supplemented controls.
• Biological plausibility. Further, we know that C15:0 directly activates AMPK, AKT and PPARs, which are mechanisms of action well established to protect cardiometabolic health. C15:0 also inhibits mTOR, JAK-STAT, HDAC-6, NF-kB, MAO-B and FAAH, which help to balance immune responses and support cognitive function.
• Replication and multiplicity of studies. Across prospective cohort studies, cell-based studies, mechanistic studies, and RCTs, C15:0’s beneficial role as a nutrient has been successfully repeated using a multiplicity of studies from different research teams. 
• Dose-response relationships. Mechanism of action studies, human cell system studies, prospective cohort studies, and RCTs have shown that the higher the C15:0 level, the greater the associated benefit (aka dose-response relationship).
• Presence of low-intake groups. Thanks to global dietary recommendations to decrease our intake of whole dairy fat, there are large swaths of populations that have had low C15:0 intake since the late 1970s, resulting in lower population-wide C15:0 levels.
• Correct temporal sequence. The benefits of prospective control studies are that they can show that people who start with higher C15:0 levels at Day 1 are more likely to have protected cardiometabolic health at Year 10. Controlled animal studies and RCTs also prove that providing C15:0 resulted in health benefits that weren’t seen in non-exposed controls.
• Low between-subject variance. A large genetic study by Otto et al. showed that there are no detectable genetic drivers for C15:0 levels, meaning that C15:0 levels are likely ubiquitously raised among individuals. This ubiquitous benefit of C15:0 as an essential nutrient has been emerging across species too, including C. elegans,  rats,  piglets, dolphins, and humans.
• Intake estimate validation. Numerous large scale studies support that we need 100 to 200 mg of C15:0 a day to maintain healthy C15:0 levels of > 0.2% (> 20 uM, > 5 ug/ml). Based on reports from the USDA and declining whole fat milk intake over the past 50 years, the average person in the U.S. today may be getting as little as 25 mg of C15:0 per day.
• Evidence of supporting early stage growth & the presence of poor growth caused by nutrient deficiency. Both prospective cohort studies of mother-infant pairs and controlled studies with multiple hallmark deficiency animal models support that lower or no dietary C15:0 among infants results in poorer growth, and supporting normal C15:0 levels results in healthier body growth and better cognitive development. This is one of the rarest and toughest criteria for a candidate nutrient to meet.
• Evidence of protecting long-term health & the presence of diseases in adults caused by nutrient deficiency. All the above supports how C15:0 protects long-term health. Additionally, the detailed pathophysiology of a C15:0 nutritional deficiency syndrome, called Cellular Fragility Syndrome, was published in 2024. This described syndrome  involves a new form of cell death called ferroptosis and may be impacting as many as 1 in 3 people globally. Importantly, the ability for C15:0 to reverse this syndrome was recently revalidated, in detail, by a second independent team.

While we typically think of randomized clinical trials as being the single gold-standard way to determine the efficacy of a molecule (aka, a pharmaceutical drug), meeting the evidence-based criteria of a nutrient that is essential to sustaining health is much harder than meeting the criteria of a drug that is targeted to treat a disease. For nutrients, it’s the totality of data that repeatedly point to the same story that counts.

Importantly, multiple independent teams have published peer-reviewed studies supporting C15:0 as an emerging essential fatty acid.

Separating the good from the bad saturated fats: a decade of Navy funding to develop a pure and science-backed C15:0 supplement.

As a result of all the above, the Office of Naval Research funded the development of a pure C15:0 supplement to support healthy aging for all.  The result? Fatty15, an award-winning and science-backed C15:0 supplement with dosing based on clinically-proven bioavailability and active concentrations to maintain and optimize our C15:0 levels to support healthy aging and longevity.

Summary

In summary, the wealth of peer-reviewed literature has definitively shown that different saturated fats behave, well, differently.  As a prime example, C15:0 has emerged not only as a beneficial odd-chain saturated fatty acid, but as a core nutrient that supports and protects healthy growth and development, as well as our long-term health.  

Cited Literature

Korbecki et al.  The effect of palmitic acid on inflammatory response in macrophages: an overview of molecular mechanisms

Sergi et al. Palmitic acid, but not lauric acid, induces metabolic inflammation, mitochondrial fragmentation and a drop in mitochondrial membrane potential in human primary myotubes

Saraswathi et al. Lauric acid versus palmitic acid: effects on adipose tissue inflammation, insulin resistance, and non-alcoholic fatty liver disease in obesity

Forouhi et al. Differences in the prospective association between individual plasma phospholipid saturated fatty acids and metabolic health: the EPIC-InterAct case-cohort study

Li et al. Saturated fatty acid biomarkers and cardiometabolic health: a meta-analysis of prospective studies

To et al. Pentadecanoic acid inhibits JAK-STAT signaling

Aabis et al. Pentadecanoic acid supports liver health by modulating oxidative stress, immune response and ferroptosis pathways in a rat

Arghavani et al. Impact of dairy intake on circulating fatty acids and associations with blood pressure: A randomized crossover trial. Nutr Metab, 

Fu et al. Pentadecanoic acid promotes basal and insulin-stimulated glucose uptake in C2C12 myotubes.

Bishop et al. Heptadecanoic acid is not a key mediator in the protection of liver health and glucose balance in mice

Venn-Watson et al. Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: could it be essential? 

Duan et al. Odd-chain fatty acid-enriched fats improve growth and intestinal morphology and function in milk replacer-fed piglets

Singh et al. Immune effects of dietary pentadecanoic fatty acid supplementation on gut health in mice

Schaefer et al. Fatty acid biomarkers and protected metabolic health: a systematic review of dose-response meta-analysis of prospective observational studies. 

Pranger et al. Fatty acids as biomarkers of total dairy and dairy fat intakes: a systematic review and meta-analysis

Mansson, HL. Fatty acids in bovine milk fat

Teng et al. C15:0 and C17:0 partially mediate the association of milk and dairy products with health risks

Thorning et al. Whole dairy matrix or single nutrients in assessment of health effects: current evidence and knowledge gaps

Van Gastelen et al. Milk fatty acid composition in lactating cows fed grass silage- or corn-silage-based diets

Serrapica et al. Seasonal variation of fatty acid profile of a mountain pecorino cheese

Yuan et al. (2022) Associations of maternal consumption of dairy products during pregnancy with perinatal fatty acid profile in the EDEN cohort study

Yuan et al. (2025) Associations between perinatal biomarkers of maternal dairy fat intake and child cognitive development: results from the EDEN mother-child cohort.

Jeong et al. Cheese consumption and cognitive health in community-dwelling older Japanese adults: the JAGES 2019-2022 cohort study

Chooi et al. Effect of An Asian-Adapted Mediterranean Diet and Pentadecanoic Acid on Liver Health: The TANGO Randomized Controlled Trial. 

Maddox et al. Forecasting the burden of cardiovascular disease and stroke in the United States through 2050

USDA. Fluid milk consumption continues downward trend, proving difficult to reverse

Venn-Watson et al. The Cellular Stability Hypothesis: Evidence of Ferroptosis and Accelerated Aging-Associated Diseases as Newly Identified Nutritional Pentadecanoic Acid (C15:0) Deficiency Syndrome. 

Dixon et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death.

Berndt et al. Ferroptosis in health and disease

Ciesielski, V. et al. Dietary pentadecanoic acid supplementation at weaning in essential fatty acid-deficient rats shed light on the new family of odd-chain n-8 PUFAs. 

Ciesielski, V. et al. New insights on pentadecanoic acid with special focus on its controversial essentiality: a mini-review.

Dornan, K. et al. Odd chain fatty acids and odd chain phenolic lipids (alkylresorcinols) are essential for diet. 

Ruan, M. et al. Free long-chain fatty acids trigger early postembryonic development in starved Caenorhabditis elegans by suppressing mTORC1. 

Venn-Watson et al. Pentadecanoic Acid (C15:0), an Essential Fatty Acid, Shares Clinically Relevant Cell-Based Activities with Leading Longevity-Enhancing Compounds.