What Are Lipase Inhibitors?

In the quest for effective weight loss solutions, lipase inhibitors have emerged as promising substances that reduce the activity of lipases [1] (the digestive ezymes which break down fat) in the intestine. By stopping Lipases from working, we shouldn't be able to asborb as many calories from fat.

In theory this should lead to weight loss. In this comprehensive guide, we will explore how lipase inhibitors work, their sources, potential side effects, and the results of long-term trials.

How Lipase Inhibitors Work?

Lipase inhibitors work by binding to lipase enzymes in the intestine, [2] preventing the breakdown of dietary fats or lipids into their fatty acid forms which the body uses. This inhibition reduces the absorption of dietary fat overall, meaning it comes out as waste, rather than being used as a source of calories. It is important to note that lipase inhibitors do not block the absorption of particular types of fat and are not absorbed into the bloodstream.

These inhibitors form a strong bond with the active part of lipases, ensuring their attachment to the enzyme.

Studies have shown that lipase inhibitors are most effective when approximately 40% of an individual's daily caloric intake is obtained from fat. [3]

Orlistat, a well-known lipase inhibitor, is said to block the absorption of 30% of total fat intake from a meal. [4] Which sounds great, but many real world applications have been a lot less favorable, especially since Orlistat has become commercially available over the counter. And there are some reasons for this.

Do Lipase Inhibitors Actually Work?

This is of course a slightly different question and the answer is yes and no, ultimately the performance depends on the diet of the individual in question. High fat diets are likely to cause weight gain and removing some of the calories absorbed does seem to work, as we’ll come on to later.

However, a person is overconsuming protein or carbohydrates, then lipase inhibitors are less effective than appetite suppressant options such as glucomannan. [5] They can however be used together.

Limitations of Lipase Inhibitors

While the results of long-term trials are promising, it is important to consider certain things when we interpret the data. The trials used rather extensive dietary counseling, which certainly influenced the observed weight loss outcomes. [6]

We also need to consider that these ideal conditions aren’t going to be the same in real-world settings. If a diet is optimized to work in conjunction with a lipase inhibitor, then they do seem to work.

But, the patients enrolled in the trials were selected for their willingness to adhere to therapy, and the weight losses reported are almost certainly not going to line up with general use.

There were also some notable lipase inhibitor side effects which a lot of people won’t put up with outside of trial settings.

Short-Term Trials

Lipase inhibitors such as orlistat have shown some promising results in short term trials. These trials, ranging from 6 weeks to 6 months, involved individuals instructed to stick to a calorie deficit with less than 30% of calories derived from fat. [7]

In comparison to diet alone, lipase inhibitors, particularly orlistat, were found to be safe and more effective in promoting weight loss, with those taking an inhibitor losing more than those taking a placebo. [8]

Long-Term Trials

However, the long term trials on lipase inhibitors were more interesting.

Pooled data from these studies, involving over 3000 subjects, showed that orlistat-treated patients lost approximately 9% of their body weight after 1 year of treatment, compared to 5.8% in placebo-treated patients. [9]

In addition to weight loss, orlistat treatment resulted in significant reductions in total cholesterol, LDL cholesterol, diastolic blood pressure, and fasting insulin and glucose concentrations.

The effects on fats within the body were actually larger than would be expected from the weight loss alone.

There have been to date two high quality large scale trials conducted in the US and Europe over a 2 year period. 

These two studies involved obese patients and those taking a lipase inhibitor lost had greater weight loss compared against the placebo group. And again they saw noticeable improvement to total cholesterol, more than would be expected from the weight loss. [10]

Sources of Lipase Inhibitors

Lipase inhibitors can be found naturally in certain plants and are also produced synthetically.

For example, lipase inhibitors have been identified in Panax ginseng, a popular herb known for its various health benefits. [11]

Additionally, active compounds with a chalcone scaffold (the shape that binds to lipase) found in Glycyrrhiza glabra, Cassia mimosoides, Glycyrrhiza uralensis, Boesenbergia rotunda, apples, and Morus alba have shown a strong effect against lipase.

The presence of lipase inhibitors in these natural sources highlights the potential of incorporating them into dietary interventions for weight management.

Potential Lipase Inhibitor And Orlistat Side Effects

The most common lipase inhibitor side effects tend to be nausea and severe cramps. [13] But, there is a much larger potential issues. 

Lipase inhibitors may affect the absorption of fat-soluble vitamins, leading to potential deficiencies. [14] It is recommended that individuals taking lipase inhibitors also take multivitamin supplements to prevent this. 

Other reported side effects include a raise in blood pressure, dry mouth, constipation, headache, and insomnia.

However, it is worth noting that overall, lipase inhibitors, particularly orlistat, have been considered safer than other anti-obesity drugs.

Lipase Inhibitors Overall

Lipase inhibitors have emerged as promising substances in the field of weight management. These inhibitors work by reducing the absorption of dietary fats, leading to weight loss in individuals. While lipase inhibitors, such as orlistat, have shown efficacy in short-term and long-term trials, it is important to note that these trials were relatively selective.


1 - https://pubmed.ncbi.nlm.nih.gov/30726031/

2 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464291/

3 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145169/

4 - https://pubmed.ncbi.nlm.nih.gov/11249520/

5 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3892933/

6 - https://pubmed.ncbi.nlm.nih.gov/10693734/

7 - https://pubmed.ncbi.nlm.nih.gov/8626884/

8 - https://pubmed.ncbi.nlm.nih.gov/9683204/

9 - https://pubmed.ncbi.nlm.nih.gov/9886891/

10 - https://pubmed.ncbi.nlm.nih.gov/10678259/

11 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6049595/

12 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659147/

13 - https://www.ncbi.nlm.nih.gov/books/NBK542202/

14 - https://pubmed.ncbi.nlm.nih.gov/12126214/

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