A humorous side note – the title of this blog, DIYPS, stands for “do-it-yourself pancreas system”, the name I gave my first automated insulin delivery (AID) system, back in 2013. An AID system doesn’t fully replicate all functions of the pancreas, so we evolved from describing it as an artificial pancreas system (APS) to automated insulin delivery (AID). But now that I have exocrine pancreatic insufficiency and am doing quite a bit of DIY around titration of enzymes….the name of this blog feels more appropriate than ever.

After I started writing about exocrine pancreatic insufficiency, I’ve gotten a lot of questions from friends and connections who think they might have EPI. (And they are likely not wrong – there are estimates that as many as 40% of people with type 1 diabetes have lowered elastase levels. Alone, that doesn’t indicate EPI, but if symptomatic and you’ve already ruled out celiac and gastroparesis, it should be (in my opinion) high on the list of things to test for. Ditto for other types of diabetes and anyone with celiac disease.) Some people, though, may have delays in getting doctor’s appointments, and/or clinicians who aren’t (yet) willing to order the elastase or other EPI-related tests without testing for other things first.

This post is for that group of folks, and anyone stumbling across this post who has seen their test results for their fecal elastase testing indicating they have “moderate pancreatic insufficiency” or “severe pancreatic insufficiency” and are wondering what they can do while they wait for their doctor’s appointment.

It’s also for people with EPI who are struggling to afford their pancreatic enzyme replacement therapy (PERT) or are limiting the number or size of meals they eat as a result of the cost of PERT.

A bit of background on why I did the math about OTC enzyme cost and why I had tested them myself

Due to the holidays in December 2021 I had a lag between getting my test results (over Christmas) and then confirming that my doctor would write a prescription for PERT, and then a delay in getting it filled by the pharmacy since they had to order it. One of the things I did during that time was read up a lot about PERT and also look to see if there were any other kinds of enzymes that would be useful to take if my doctor didn’t want to prescribe me PERT. I found out that PERT contains THREE types of enzymes, and together they’re known as pancrelipase. Pancrelipase contains lipase (helps digest fat), protease (helps digest protein), and amylase (helps digest starches and other complex carbohydrates). It’s typically made from ground up pig pancreas, which is one of the reasons that PERT costs so much. Amylase from non-pancreatic sources is not widely available for human consumption, but there are some other ways to make protease and lipase. And it turns out that these standalone enzyme versions, often produced by microbes, are available to buy over the counter.

While waiting for my test to be ordered, I went ahead and ordered a standalone lipase product that is over the counter (OTC). In part, that was because some of the reviews for lipase talked about having EPI and how they were only sensitive to lipase, and so this was a viable and cheaper alternative for them rather than taking PERT with all 3 enzymes, since they didn’t need that. Based on my experience with FODMAPs and trying an enzyme powder to target fructans (which did help me some), it seemed like trying small doses of lipase would help if I did have EPI, and likely wouldn’t hurt even if I did not have EPI.

And it helped. It didn’t reduce all my symptoms, but even minor doses (3000 units of lipase) made a noticeable difference in my symptoms and I got a sense for what meals were more fat and protein-laden than others.

As a result, when my test results came in and I was on the borderline for moderate EPI, I agreed with my HCP that since it likely wouldn’t hurt to take PERT (other than the cost), and it would be obvious if it helped, that I should try PERT.

So having done the tests with OTC (over the counter) lipase was helpful for deciding to take PERT and advocating for my prescription.

And it turns out, wow yes, I do have EPI and do definitely need PERT (more about my first two weeks on PERT here).

And as I wrote here, because I had the OTC lipase sitting around, even after I finally had access to PERT, I eventually titrated my dosing and calculated separate ratios for lipase:fat and protease:protein, so I can decide for every meal or snack whether I need one full PERT (all three enzymes), two PERT, a PERT plus some lipase (and how much), or just a standalone OTC lipase. The cost differs greatly between those options: one PERT might be $9 and a standalone lipase pill around $0.26. You can’t break apart a PERT (e.g. take only half), so adding a few lipase is a cost-effective approach if you don’t need more protease or amylase and the OTC lipase works for you.

Some of the reasons to explore over the counter enzymes with exocrine pancreatic insufficiency or a suspected case of EPI

One interesting thing about one of the main tests (fecal elastase) used to assess EPI is that it is NOT impacted by taking enzymes. Someone who is started on pancreatic enzyme replacement therapy (PERT) can still have an elastase test without stopping taking PERT. So if someone had an inconclusive result or was borderline and started taking PERT, but their doctor wanted to re-test again, the use of PERT would not affect the test. The same goes for other types of enzymes.

I’ve realized that the following groups of people might want to investigate various OTC enzyme options:

• Someone who has been diagnosed with EPI, but has done careful testing with meals of various sizes (low fat & high protein, high fat & low protein, etc.) to determine that they really only need lipase, may benefit from cheaper lipase-only OTC options.
• Someone who has a test result for EPI but doesn’t yet have an appointment with their doctor or a prescription for PERT could start taking some OTC enzymes for quicker symptom relief, even if they ultimately want to use PERT for all their enzyme needs once they get their prescription filled.
• Someone diagnosed with EPI who cannot afford the ideal dose of PERT that they need for their meals and snacks, may want to calculate the out of pocket costs for OTC lipase (not covered by insurance) vs the cost of PERT with or without insurance.
• Someone who can’t get tested for EPI, but suspects they have EPI, might want to also explore OTC lipase and/or OTC multiple enzyme products.

However, not everyone with EPI will want OTC enzymes. Some people may have great insurance coverage, so their PERT costs them less than $9 a pill. OTC enzymes are not covered by insurance, but I’d still do the math and assess what your standard cost is per pill, because it may surprise you how cheap add-on OTC lipase is vs. your insurance deductible or copay to take additional PERT for larger meals. The other reason some people may not want to take OTC enzymes is the pill burden: OTC doses tend to be smaller, so you usually need to take more pills to cover the same meal as a single, larger PERT.

Picking what enzymes (in general, or specific brands) work for you

I often see a variety of OTC enzyme products recommended in peer groups on social media for EPI. There are no studies that I can find assessing the efficacy of these OTC brands (meaning, how good they are). I would be very cautious when trying different single or multiple enzyme products and keep a careful log of your symptoms from before enzymes as well as symptoms at every meal that you take enzymes, and your bathroom results afterward. This can help you assess OTC enzymes as well as PERT if you get access to it. By having a good log of your symptoms, you can tell if you’re taking enough enzymes (OTC or PERT) or if you’re developing new symptoms (which could be a side effect of whatever brand/type you are taking).

There are multiple brands and sizes of PERT, too, and it’s possible that a filler product or how the PERT is made by one brand doesn’t work well for you. If that’s the case, you can try another brand of PERT.

The same goes for OTC enzymes: it is very possible some types of pills may be made with ingredients that could bother you and cause symptoms themselves. You should definitely be very cautious if you go this route and explore small doses and ensure no side effects (no new symptoms) before increasing any doses.

When I search for lipase, it’s easy to find standalone lipase (here is an example, as an Amazon affiliate link). When I search for protease, it’s more common to find products that are multiple enzymes (e.g. lipase AND protease AND other random things that are “good for digestion”). Personally, I’m very wary of anything OTC that’s described as “digestive enzymes” and prefer to stick to products that only have the ingredients I’m looking for.

In diabetes, we often say “your diabetes may vary” (YDMV), indicating that different people can have different experiences.

In EPI, it’s no different – “your digestion may vary” and it’s important to test and record and find what works for you, and to find a balance of reducing or eliminating symptoms with enzymes in a cost-effective way that you can afford.

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(PS, if you didn’t see them, I have other posts about EPI at DIYPS.org/EPI – including one about PERT Pilot, the first iOS app for Exocrine Pancreatic Insufficiency! It’s an iOS app that allows you to record as many meals as you want, the PERT dosing and outcomes, to help you visualize and review more of your PERT dosing data!)

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You can also contribute to a research study and help us learn more about EPI/PEI – take this anonymous survey to share your experiences with EPI-related symptoms!

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I previously wrote about my experience figuring out that I have exocrine pancreatic insufficiency (known as EPI or PEI), and also a little bit about starting on pancreatic enzyme replacement therapy (PERT). I talked briefly about the method I was using to figure out the right amount of PERT for me, but I realize that there’s a lot more detail I could provide about how to titrate enzymes in general, and not just PERT.

Some background first, though. When I write about PERT (pancreatic enzyme replacement therapy), I am talking about the FDA-approved class of drugs (called “pancrelipase”) that contain THREE types of enzymes, which the FDA calls “pancreatic enzyme products” or PEPs. Pancrelipase contains lipase (helps digest fat), protease (helps digest protein), and amylase (helps digest starches and other complex carbohydrates). As of 2010, all pancrelipase products that are marketed for EPI must be FDA approved.

Any time I refer (here or in other blog posts) to other enzyme products (either single enzyme or multi-enzyme), I’m referring to over the counter products that are not FDA approved.

Why does FDA approval matter for PEPs? FDA approval is essentially a rubber stamp saying you can trust the FDA to have validated that the companies making these products are making them as they describe them, meaning if they say they have 25,000 units of lipase, they actually have 25,000 units of lipase in them. (And protease and amylase). FDA-approved PEPs used in PERT are made from ground up pig pancreas (really), which is why they’re expensive. There is no generic PEP or PERT. (FDA also has a nice page here explaining the importance of understanding what is and is not an approved PEP/PERT product, and it also explains the brands that are currently approved and the differences between them.) This matters because when you talk about the cost people will probably suggest a “generic” of PERT, but there isn’t one.

However, there are non-FDA-approved over the counter enzyme products. They do exist, but because they have not been vetted by the FDA, I (and you!) should be wary about trusting them when they say they contain X units of lipase or any other enzyme product. Additionally, there are no studies (that I can find) comparing the efficacy between over the counter enzymes (single or multi-enzyme products) and FDA-approved PERT. (If you have found such a study, please leave a comment!)

So does that mean you can’t take them? No, I’m not saying that. What I am saying is you should only try other products with enzymes if you are willing to carefully test and vet FOR YOURSELF whether they work FOR YOU or not. (P.S. – did I mention I’m not a doctor? This is not medical advice; for medical advice, talk with your doctor. Although, doctors may not be aware of the over the counter enzyme options either, and this post might be worth sharing with them as well).

Three goals for optimally titrating enzymes for exocrine pancreatic insufficiency

I have three goals for getting my PERT dose titrated well.

• First, get enough enzymes (through PERT) to reduce all symptoms.
• Second, test and assess my lipase:fat and protease:protein ratios so I can figure out how to optimally dose enzymes for new meals of different amounts of fat and protein.
• Third, optimize for reducing cost with enzymes, through a combination of supplementing PERT with standalone lipase and/or using lipase for fat-only snacks.

Here’s an example of how you might consider vetting over the counter enzyme products, and using them to supplement your FDA-approved (and hopefully insurance-covered) PERT:

As I mentioned earlier, I titrated and found out that my current dose of PERT covers about 30-40 grams of fat and 30 grams of protein. Some individuals only need support in digesting fat (e.g., need only lipase), but I have found that my body also needs support in digesting protein. (However, I don’t appear to need much amylase for carbohydrates.) Therefore I am tracking what amount of fat and protein I am eating with every meal. A 25,000 (lipase) dose of my PERT also contains enough protease to cover 30 grams of protein. Sometimes, I eat higher (>30-40g) fat meals that mean I need more lipase. So I would need two pills of the current dose of PERT, because 25,000 only covers ~30-40g of fat (FOR ME).

But – what if there was another way to get additional lipase without needing a full second pill of PERT, if I don’t need the additional support for more protein for this meal?

Enter over the counter enzyme options. In this example, a single enzyme option for lipase. Here is an example (Amazon affiliate link) to a standalone, single enzyme lipase product that is available as an over the counter product.

I personally have experimented with using standalone over the counter lipase to supplement my PERT dose, for the reason described above (needing more lipase but not necessarily needing more protease or amylase). The reason I would choose standalone lipase has to do with cost.

PERT, being ground up pig pancreas, is expensive. There is no generic for PERT! However, there have been methods to develop lipase from microbes as well as other sources beyond animals. Thus, it is possible to have a standalone source of lipase that is a lot cheaper than PERT. How much cheaper? Well, the bottle linked above when I calculated this was $23.50 for 90 pills. One pill each contains roughly 3,150 units of lipase (again, caveat from above about trusting the amount in over the counter products). That means each pill ($23.50/90 pills) is $0.26 USD, and each 1,000 units of lipase is roughly $0.08.

This math is then helpful to compare the cost of PERT. Depending on the size of prescription PERT, you might see a prescription anywhere from 3,000 to 25,000 to 36,000 units (depending on the brand, they have different amounts, but they are all measured based on units of lipase). Using GoodRx, you can generally compare retail prices of medications, such as this search for 24,000 PERT of one brand (90 capsules) or this search for 25,000 PERT of a different brand (also 90 capsules). Both of them are in the ballpark (for 90 capsules each) of $700-900, so let’s use $800 for 90 capsules for simple math. The per-pill price is $8.89 ($800/90 pills). The per-1,000 unit of lipase cost depends on whether you are using the 24,000 PERT ($8.89/24) or 25,000 PERT ($8.89/25) option, but those are roughly $0.37 and $0.36 per 1000 units of lipase.

So if you were to consume a meal that was ~10g of fat above your current PERT dose, and you didn’t need additional protein support, it would be cheaper to add on additional lipase (at $0.08 per 1000 units of lipase) as a standalone enzyme product instead of an additional PERT (which is, per our estimates, ~$0.36 per 1000 units of lipase). You don’t get to break apart a PERT (It can’t be cut in half, for example), so the per-pill cost is the better comparison. Adding a 3000-ish unit lipase onto your meal to cover an additional 10g of fat costs $0.26, and a second PERT is $8.89.

Therefore, a meal that needs 28,000 lipase is cheaper as 1 PERT and 1 extra standalone lipase rather than 2 PERT.

This of course assumes you have tested the standalone lipase and found that it works for you. I personally have done so and found that standalone lipase of the brand I chose works for this purpose (there are many brands and sizes: again, test what works for you), so I can titrate my meals as PERT+lipase, or even take 1-2 lipase (depending on the fat content) for a snack that’s mainly fat. However, again, a caveat that I personally am sensitive to protein and am tracking everything that I’m eating, so I know my personal math very well. Typical PERT dosing and recommendations is to take “2 or more” for meals or “1-2 for snacks”, but that completely ignores how much fat and protein is in the meals, and might be significantly undertreatment or overtreatment for you.

Why does undertreatment matter? Well, you get symptoms. Those are no fun.

Why does overtreatment matter? Well, you can get constipation. (I haven’t had it, but it also doesn’t sound like fun).

My approach was making sure my meals were covered first with prescription PERT, then evaluating additional standalone products that I could use to supplement or replace PERT depending on what I was eating, so I could prioritize reducing symptoms and then for improving the cost required to achieve that.

There are other standalone enzyme products, including products containing multiple enzymes. If you join one of the Facebook groups for EPI, you’ll see people recommencing various names of enzymes for over the counter products. But again, you really should test things and see if they work for you. Read all the ingredients on any product you’re taking. A lot of times you can search for lipase and you’ll get a multiple-enzyme product. And that product may have additional ingredients or fillers that don’t sit well with you. You may even find that one brand of prescription PERT might not work for you, whereas another one does.

My suggestions include:

• Carefully test any product, whether it’s PERT or over the counter enzymes. Keep a good log of your post-meal symptoms and next-day symptoms (e.g. bathroom results) and try different meals with different amounts of fat and protein.
• If you have symptoms regularly with a certain amount of enzymes, it could be either that this particular brand (over the counter or even prescription PERT) does not work well for you, OR that you are not taking enough enzymes to cover your needs.
• If in doubt, talk with your doctor. They may/not have opinions on over the counter products, especially if they haven’t had other patients reporting back what is working for them or not, since there are no studies on those particular brands (and of course, they’re not FDA approved). But with approved PERT, they should be able to give you some more input on how to increase your dose or change your prescription to adjust. Having the data on how much fat and protein you’re eating and what results you’ve been getting could help you (and them) get to a more optimal dose more quickly.

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(PS, if you didn’t see them, I have other posts about EPI at DIYPS.org/EPI)