Bile Acids as a Hormonal Factor in PCOS

A study was recently conducted on circulating bile acids in women with PCOS.

This is the very first study [1] of its kind, and involved 37 women with PCOS matched to women without the condition. Researchers measured conjugated bile acids, and these were found to be elevated in patients with PCOS. 

Additionally, high acid levels were also associated with higher serum levels of testosterone and androstenedione (another androgen) in the women.

Are you intrigued yet? If not, let’s take a quick look at bile acids, and their function in digestive health and wellbeing.

Bile Acids

What are Bile Acids?

These acids are made from cholesterol in the liver. They’re then linked up with glycine or taurine (amino acids) in a process known as “conjugation”. After that, they’re converted by the microbiome.

In fact, they’re emerging as gut microbiome regulators, as they can have direct antimicrobial effects. Furthermore, reduced levels in the gut are associated with bacterial inflammation, as excess levels cause other bacterial species’ overgrowth.[2]

These interesting molecules used to be thought of as mere bystanders in fat breakdown, or mainly limited to fat digestion. Now, in addition to their impact on the microbiome, they’re being recognized as hormones. These endocrine-signalling molecules in our body affect more than the gut. It turns out that they travel in the blood to impact other areas.

Increased serum bile acids have been found in obesity, type two diabetes, and non-alcoholic fatty liver disease

Bile in PCOS

How Does it Apply to PCOS?

This study found that women with PCOS had significantly increased bile acids in their blood, compared to those without the condition. It also discovered that these high levels correlated with increased testosterone levels: a worse overall PCOS picture.

This is the first description of bile acid profiles in PCOS.

Impacted Areas:

Disregulated acids can promote chronic inflammation and increased intestinal permeability (leaky gut). These may impact PCOS as they can contribute to chronic low-grade inflammation.

What do Bile Acids do?

They work on the Farnesoid X receptor, which has hormonal actions throughout the body. Because these acids are potentially toxic to cells, their concentrations are typically regulated well by the body.

There’s actually a feedback mechanism in the liver that prevents too many acid syntheses when levels are too high.

In cholestasis (dysregulated or sluggish bile flow)—which is more commen in women with PCOS and other metabolic conditions—there’s often an increase in bile acids in the blood. This is because bile release is not coordinated properly: it should be released according to timing and food intake.

Additionally, it’s because bile may also contain excessive cholesterol concentrations, due to the metabolic health issues common in PCOS .

Protein for PCOS

Overall Effects of Increased Bile Acids:

These increased blood levels blood may contribute to overall hormonal disruption. This is because the FXR receptor has been found within the ovary’s granulosa cells, and this may be how it raises testosterone.

It’s also been found that increased bile acid levels can cause insulin resistance. [3]

Other research has found them to increase cortisol secretion (the stress hormone) and adrenal androgen production in mice. This could potentially contribute to the androgen excess in PCOS. [4]

Symptoms of Dysregulated Bile Acids:

  • Difficulty digesting fats
  • Bloating and gas after eating
  • Nausea and burping after eating
  • Fatty Liver Disease
  • Pale stools
  • Loose stools shortly after eating

Tests:

There can be issues with biliary function, while testing is negative.

  • ALT (liver function)
  • Total bile acids
  • Bilirubin
  • Ultrasound (may be negative)
  • Lipid panel
  • Fasting Insulin

What can you do?

Maintaining your Circadian rhythm is key! Stressors that alter sleep and eating patterns influence the microbiome, and can disrupt the normal acid production and release patterns.

  • Sleep: get enough sleep
  • Increase Fibre intake: 35 grams of mixed soluble and insoluble fibre per day will decrease resorption of deoxycholic acid. This helps to keep cholesterol concentration in the bile lower.
  • Choline (or phophatidylcholine) supports healthy biliary function.
  • Include protein with each meal, to keep blood sugar optimal.

References:

  1.  Zhang B, Shen S, Gu T, Hong T, Liu J, Sun J, Wang H, Bi Y, Zhu D. Increasedcirculating conjugated primary bile acids are associated with hyperandrogenism inwomen with polycystic ovary syndrome. J Steroid Biochem Mol Biol. 2019 Mar5;189:171-175.
  2. 10.1097/MOG.0000000000000057
  3. Zhang B, Shen S, Gu T, Hong T, Liu J, Sun J, Wang H, Bi Y, Zhu D. Increasedcirculating conjugated primary bile acids are associated with hyperandrogenism inwomen with polycystic ovary syndrome. J Steroid Biochem Mol Biol. 2019 Mar5;189:171-175.
  4. Liu L, Panzitt K, Racedo S, Wagner M, Platzer W, Zaufel A, Theiler-Schwetz V, Obermayer-Pietsch B, Müller H, Höfler G, Heinemann A, Zollner G, Fickert P. Bile acids increase steroidogenesis in cholemic mice and induce cortisol secretion in adrenocortical H295R cells via S1PR2, ERK and SF-1. Liver Int. 2019 Jan 21.