Propionate (also called propionic acid) is a three-carbon short-chain fatty acid that accounts for approximately 25% of total SCFA production in the human gut. Unlike butyrate, which is primarily used by colon cells, propionate is absorbed and transported to the liver, where it exerts significant effects on metabolism.[1] Propionate is a dietary fiber fermentation product that may help combat obesity by suppressing appetite and regulating adipogenesis through G-protein coupled receptor signaling.[2]
The Liver Connection
After absorption in the colon, propionate travels via the portal vein to the liver, making it the SCFA with the most direct influence on hepatic metabolism:
Gluconeogenesis Regulation
Propionate serves as a substrate for gluconeogenesis (glucose production) in the liver. However, it paradoxically helps regulate blood sugar by:
- Competing with other gluconeogenic substrates
- Reducing hepatic glucose output overall
- Improving insulin sensitivity
Cholesterol Synthesis
Propionate inhibits cholesterol synthesis by reducing the activity of HMG-CoA reductase—the same enzyme targeted by statin medications. Orally supplied propionate reduces urinary glucose excretion, fasting blood glucose, and liver cholesterol pools.[3] This may contribute to the cholesterol-lowering effects of high-fiber diets.
Lipid Metabolism
Studies suggest propionate reduces hepatic lipogenesis (fat production) and may help prevent fatty liver disease [^hosseini2011].
Appetite and Weight Management
One of propionate's most exciting properties is its effect on appetite regulation. Research has shown that propionate [^chambers2015]:
- Stimulates gut hormones: Propionate triggers release of GLP-1 and PYY, hormones that signal fullness
- Reduces food intake: Studies show propionate supplementation leads to reduced calorie consumption
- Affects reward centers: Brain imaging reveals propionate reduces activity in reward centers when viewing high-calorie foods
- Supports weight maintenance: Long-term supplementation helps prevent weight regain after dieting
A landmark 2015 study found that delivering propionate directly to the colon (via inulin-propionate ester) significantly reduced weight gain and improved appetite control in overweight adults.
Propionate Production Pathways
Gut bacteria produce propionate through two main pathways:
Succinate Pathway
Used primarily by Bacteroides species, this pathway converts carbohydrates to succinate, then to propionate. It's the dominant propionate production route in humans.
Acrylate Pathway
Used by some bacteria including Akkermansia muciniphila, this pathway can utilize lactate as a substrate.
Propanediol Pathway
Certain bacteria can produce propionate from deoxy sugars like fucose and rhamnose, found in dietary and mucin glycans.
Key Propionate-Producing Bacteria
- Bacteroides species: The main propionate producers in most people
- Akkermansia muciniphila: Produces propionate from mucin degradation
- Veillonella species: Converts lactate to propionate
- Phascolarctobacterium species: Utilizes succinate from other bacteria
- Dialister species: Important cross-feeding partners
Health Benefits
Metabolic Health
- Improved glucose tolerance
- Reduced insulin resistance
- Lower fasting blood sugar levels
- Better lipid profiles
Cardiovascular Protection
- Reduced cholesterol synthesis
- Anti-inflammatory effects on blood vessels
- Potential blood pressure regulation
Immune Modulation
- Anti-inflammatory properties
- Influences immune cell function
- May protect against autoimmune conditions
Potential Anti-Cancer Effects
- Inhibits proliferation of certain cancer cells
- May work synergistically with butyrate
Dietary Sources and Boosting Production
Foods That Increase Propionate
- Pectin-rich foods: Apples, citrus fruits, berries
- Oats and barley: Rich in beta-glucan
- Root vegetables: Carrots, beets
- Legumes: Beans, lentils, peas
- Green bananas: Resistant starch source
Supplementation Options
- Inulin-propionate ester (IPE): A targeted delivery system used in research
- Calcium propionate: Used as a food preservative, but dietary amounts are small
- Prebiotic supplements: May indirectly boost propionate production
Testing and Interpretation
Propionate can be measured in stool through organic acid testing. Considerations include:
- Propionate levels reflect recent dietary fiber intake
- Balance between SCFAs may be more important than absolute levels
- Low propionate with adequate fiber intake may suggest dysbiosis
- Consider alongside microbiome testing to identify propionate-producing bacteria
Propionate vs. Butyrate
While both are beneficial SCFAs, they have distinct roles:
| Aspect |
Propionate |
Butyrate |
| Primary target |
Liver |
Colon cells |
| Main effect |
Metabolic regulation |
Gut health |
| Production |
~25% of SCFAs |
~15% of SCFAs |
| Key producers |
Bacteroides |
Faecalibacterium |
A healthy microbiome produces both in appropriate amounts, and dietary fiber variety ensures adequate production of all SCFAs.
