Fatty 15 and Renal Disease

In pursuing optimal health, longevity and well-being, we have seen a surge in interest in dietary supplements and nutritional protocols targeting these areas. Among these emerging trends is the interest in omega-15 fatty acids and pentadecanoic acid (C15:0). C15:0 is scientifically referred to as pentadecanoic acid. It represents a lesser-known omega fatty acid family. C15:0 is an odd-chain saturated fatty acid present in trace levels in dairy fat and ruminant meat, as well as some types of plants and fish.  The potential health benefits of C15:0 include metabolic health support, cardiovascular support, healthy aging and protecting cells against age-related oxidation. It has been found to be better and safer in repairing cells and restoring cellular health when compared to omega 3.

Large, prospective human cohort studies have shown that higher C15:0 blood concentrations are associated with lower risks of developing chronic conditions such as type 2 diabetes, cardiovascular disease and heart failure. Studies also show that higher levels of dietary intake of C15:0 are linked to lower mortality, higher longevity, lower risk of inflammation, gestational diabetes, hypertension, non-alcoholic fatty acid disease, less severe non-alcoholic steatohepatitis and chronic obstructive pulmonary disease.

C15:0 is a vegan-friendly, plant-based ingredient found in the supplement Fatty15.

Biomarkers of dairy fat intake, incident cardiovascular disease, and all-cause mortality: A cohort study, systematic review, and meta-analysis | PLOS Medicine

A prospective and longitudinal study of plasma phospholipid saturated fatty acid profile in relation to cardiometabolic biomarkers and the risk of gestational diabetes – ScienceDirect

Broader and safer clinically-relevant activities of pentadecanoic acid compared to omega-3: Evaluation of an emerging essential fatty acid across twelve primary human cell-based disease systems | PLOS ONE

 

Fatty 15 and Renal Disease
Fatty 15 and Renal Disease

What Are Essential Fatty Acids?

Essential fatty acids (EFAs) are types of fats that are essential for our health. However, they cannot be synthesised by our body, meaning they must be obtained through dietary sources.

There are only three known essential fatty acids: omega 3 (alpha-linolenic acid), omega 6 (linoleic acid) and now C15:0.

There are two main types of EFAs:

  1. The primary three omega-3 acids are;
    • Alpha linoleic acid (ALA)- This is found in plant sources such as flaxseeds, chia seeds, hemp seeds and walnuts.
    • Eicosapentaenoic acid (EPA) – Found in fatty fish such as salmon, maceral, sardines and anchovies.
    • Docosahexaenoic acid (DHA)- Also found in fatty fish, especially high in fish oil supplements.
  1. Omega 6 fatty acids-Omega-6 fatty acids are polyunsaturated fats essential for health.
    • Linoleic acid (LA)- LA is found in vegetable oils such as soybean, corn, sunflower, and safflower.

An excessive intake of omega-6 to omega-3 fatty acids may contribute to inflammation and certain chronic diseases if not balanced properly.

  1. C15:0 (pentadecanoic acid) A healthy essential odd-chain fatty acid.

Odd or even, essential fatty acids are named for the number of carbon atoms they carry, and our body will break them down in different ways.

Even chained fatty acids are fatty acids composed of an even number of carbon atoms in their aliphatic chain. These include palmitic acid (C16), stearic acid (C18) and arachidonic acid (C20).

An increase in even chained fatty acids is associated with an increased risk of:

  • Inflammation
  • Heart disease
  • Type 2 diabetes

Higher levels of odd-chain saturated fatty acids, such as C15:0, have been associated with better heart health, healthy metabolism, liver health, red blood cell health, and immune system balance.

 

Kidney disease and C15 essential fatty acids

Source-D1: Human Nutrition (Core) – AMAZING WORLD OF SCIENCE WITH MR. GREEN (mrgscience.com)

The Discovery of C15:0 as a Good Fat

Dr Stephanie Venn-Watson, a veterinary epidemiologist, initially discovered C15:0 as a beneficial ingredient while she was studying how to assist older navy dolphins in living healthier, longer lives. Stephanie and her Navy team discovered some dolphins aged healthier than others. The team hypothesized that the higher omega-3 fish diets likely predicted the healthiest aging dolphins.  However, they unexpectedly discovered that it was not the higher levels of omega-3 but instead higher levels of C15:0.

To observe how the dolphins were affected by the changes in the ocean and the fish they consumed, they looked at two groups. One from San Diego, CA and the other from Sarasota, FL. They noted that the Californian pod had more age-related conditions to the Florida pod. When the California pod switched to fish with higher levels of C15:0, their age-related conditions stabilized, as did their cells. With this discovery, C15:0 was developed, and Stephanie and her husband worked with the Navy to create the pure C15:0 ingredient (FA15) and the world’s first C15:0 supplement, Fatty15.

 

Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: could it be essential? – PMC (nih.gov)

Studies show that C15:0 has mTOR-inhibiting and AMPK-activating activities shared with rapamycin and metformin.  The same study showed, at their optimal doses, C15:0 and rapamycin had 24 shared, cell-based activities across 10 (83%) out of 12 cell systems, including anti-inflammatory, antifibrotic, and anticancer activities.  C15:0 should, by definition, support an expanded health span.

C15:0 & Mitochondria

Mitochondrial dysfunction and increased production of reactive oxygen species (ROS) are key issues in the degradative process of aging, cardiometabolic disease, chronic kidney disease, and other chronic disease processes. Fatty acids can affect mitochondrial function; the authors found reduced mitochondrial reactive oxygen species production in stressed human cell systems supplemented with C15:0 at 10, 20, and 50 µM. This was compared to non-supplemented controls.

We know mitochondria play a very important role in kidneys!

Energy demands within the renal cells are tailored to each specific cellular function, and cellular energy demands are met mainly by mitochondria. Mitochondrial dysfunction is associated with almost all types of kidney disease.

Mitochondrial dysfunction and abnormalities affect some cellular pathways, leading to increased oxidative stress, apoptosis, fibrosis, and microvascular loss. To perform their primary function, regulating body fluid composition through the filtration and reabsorption of material, kidneys consume roughly 7% of the body’s daily ATP expenditure.

Mitochondrial dysfunction in kidney diseases – ScienceDirect

Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: could it be essential? – PMC (nih.gov)

C15:0 & Metabolic Syndrome

Metabolic syndrome is characterised by a group of conditions that occur together, increasing the risk of increased blood pressure, high blood sugar, and excess body fat around the waist paired with abnormal cholesterol or triglyceride levels. C15:0 has been shown to improve metabolic health. Chronic low-grade inflammation driven by proinflammatory chemokines and cytokines has been found to contribute to metabolic syndrome and the aging process. The authors found that supplementing daily with C15:0 and C17:0 lowered the proinflammatory states of obese mice with metabolic syndrome. Supplementation also lowered pro-inflammatory biomarkers in primary human cell systems, mimicking chronic inflammation.

C15:0 and C17:0 were found to lower monocyte chemoattractant protein 1 (MCP-1), which is a pro-inflammatory chemokine. C15:0 was also found to lower proinflammatory chemokines (CXCL9, 10 and 11), cytokines (IL-6, -17A), and adipokines (platelet activation inhibitor 1, or PAI-1). Note that MCP-1 can be activated by even-chain saturated fatty acid (ECFA), C16:0, contributing to the chronic inflammation seen in chronic cardiometabolic disease.  The studies suggest that lowering of proinflammatory states, including lowered MCP-1, by OCFAs may contribute to lower adipokines and a lower risk of type 2 diabetes, cardiovascular disease, pancreatic cancer, and mortality. A daily oral dose of C15:0 over a 12-week period was also found to lower total cholesterol and glucose in an in vivo model with metabolic syndrome.

Biomarkers of dairy fat intake, incident cardiovascular disease, and all-cause mortality: A cohort study, systematic review, and meta-analysis | PLOS Medicine

C15:0 Reduced Proinflammatory and Profibrotic States in Human Cell Systems

The same study tested OCFAs (C13:0, C15:0, and C17:0) and ECFAS (C14:0 and C16:0) for anti-inflammatory and antifibrotic activities. C15:0 was found to have dose-dependent anti-inflammatory activity. It was found to reduce MCP-1 and have antifibrotic activities, including reduced Collagen I, plasminogen activation inhibitor 1 (PAI-1), and 72-hour fibroblast proliferation.

The study supports that a minor increase in C15:0 concentrations (e.g. from 2.2 µM to 6.7 µM) can positively impact its anti-inflammatory and antifibrotic activities.

Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: could it be essential? – PMC (nih.gov)

C15 and CKD

Source Saturated Fats and Health: A Reassessment and Proposal for Food-Based Recommendations: JACC State-of-the-Art Review | Journal of the American College of Cardiology

Dozens of nutritional papers on saturated fats and how they affect our health have been written. The problem has been that while we have continued to hear about the negative impact of saturated fats, we have not heard enough about the positive impacts. As you can see from above, there are good saturated fats, these are the odd chained saturated fatty acids and they have many positive benefits for our health and longevity.  Further studies will be beneficial in evaluating the potential impact of decades of reduced intake of OCFA-containing foods as contributors to C15:0 deficiencies and the increased susceptibility to chronic disease.

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