Longevity Supplements: How many capsules are you swallowing each day?

Question on my mind: Are capsules hurting my gut microbiome?

When reading studies on longevity and healthspan, I often end up buying a supplement that I think will make a change - improve health, give me energy, prevent a future disease…

Yep, I’ve ended up with a drawer full of supplement bottles.

About five or six years ago, I read a study on how substances that act as surfactants and emulsifiers, such as carboxymethylcellulose (CMC) and polysorbate 80, can thin the mucosal barrier.[ref] This is more of a problem for people with specific genetic variants that increase inflammation in response to the gut bacteria moving closer to the epithelial gut lining when the mucosa is thinned. (Genetic Lifehacks article on it: Leaky Gut Genes: Emulsifiers in Processed Foods)

In addition, a thinner mucosal barrier may allow digestive enzymes to be absorbed and circulate. (Circling back to my Longevity Lifehacks article on autodigestion as a root cause of aging.)

Carboxylmethylcellulose (CMC) is classified by the FDA as ‘generally regarded as safe’ and allowable up to 2% in food products. It’s usually derived from wood pulp or cotton processing. However, a study showed that 15g/day of CMC caused significant changes to the composition of the gut microbiome, with about 20% of the participants ending up with gut inflammation and “stark alterations in microbiota composition”.[ref]

This brings me to the conundrum….

Capsules used to be made of gelatin, but with the rise of people looking for vegan products, manufacturers switched to vegetarian capsules made of plant fiber (cellulose). Some softgels are also using alternatives to gelatin, including carboxymethylcellulose and carageenan.[ref]

Go check the label on your favorite supplements. What are they encased in?

Many supplement brands that I like pack everything inside a hypromellose (HPMC, hydroxypropyl methylcellulose) capsule or contain carboxymethylcellulose as a filler. Tablets often contain carboxymethylcellulose, as do prescription medications.

For some prescription medications, the manufacturer formulates them with polysorbate 80 or other surfactants, such as sodium lauryl sulfate, specifically to thin out the mucosal barrier for better absorption.[ref][ref][ref] (I’m not suggesting that you stop a prescription medication, just wanting to point out possible additive effects of taking prescription medications along with natural supplements.)

To make it a bit more complicated, there are different formulations, different terminology, and a lot of questions as to the effect on the gut mucosal barrier. [ref]

I reached out to a couple of the major supplement companies with questions. Interestingly, one responded with “We provide comprehensive information on our product labels, adhering to regulatory requirements for ingredient disclosure and labeling. However, any detail beyond what is listed is proprietary and confidential. Unfortunately, we are unable to disclose further details about the capsules.”

I’m left wondering whether the supplements that I take in a hypromellose, carboxymethylcellulose, methylcellulose, or HPMC capsule are harming my gut mucosa. And, well, what else is in them that isn’t required to be on the label…

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Let’s take a look at what studies on different types of capsules show:

First up - microcrystalline cellulose, which is added to some supplements for bulk. Jarrow Formulas confirmed via email that the source of the microcrystalline cellulose fiber in their supplements is either pine or cotton. Studies in animal models of IBD do not show that it exacerbates inflammation in the gut, and instead, the animal microbiomes use it as a source of fiber. Human studies show that some people have microbiomes that can digest microcrystalline cellulose (producing methane), but that about 60% of people don’t have microbes to digest it, and it passes through.[ref]

HPMC capsules are mainly described in glowing terms because they are vegan and made from “plant fiber”. Some HPMC capsule manufacturers use carrageenan as a gelling agent, but not all manufacturers use it.[ref] (Jarrow HPMC capsules do not use carrageenan per an email with their customer service.)

A 2021 study showed that HPMC causes an irreversible decrease in gut microbial diversity. Essentially, the bacterial diversity decreased with HPMC and didn’t bounce back within 48 hours.[ref - open access, worth reading]

The question that I’m left with here is whether the amount of HPMC in a handful of capsules is enough to make a real change in the microbiome? The study used a concentration of 0.1%. If I’m taking a couple of capsules along with a meal, that should be less than 0.1%. However, I sometimes take supplements on an empty stomach (known as the ‘whatever time I remember to take the supplement’ dosing regimen), and that would be more than 0.1% if I have been fasting.

Pullulan is also used for making vegan capsules. Pullulan is a polysaccharide produced by the fungus Aureobasidium pullulans. It is available in regular hard capsules and in softgels, with sorbitol and glycerol used as a plasticizer.[ref] The one gut-related study that I found on pullulan showed that it increased acidity and reduced Bifidobacteria and Lactobacillus species a bit.[ref] Again, I’m not sure that the amount found in a capsule is enough to significantly affect the microbiome composition.

Both HPMC capsules and gelatin capsules dissolve in the stomach pretty rapidly (6-9 minutes).[ref] Enteric coatings on supplements help to keep the capsule from dissolving before reaching the intestines. The coatings can take many different forms, with different plasticizers used as coatings. For example, cellulose acetate phthalate is used as one form of enteric coating, while hypromellose phthalate is another option.[ref][ref]

To be honest - I never even thought about phthalates being used as coatings for supplements (especially probiotics). I’m not real thrilled with the idea of deliberately consuming more phthalates.

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So…. what are the options here?

First, decide if you think the problem of an altered gut microbiome from different cellulose options in capsules is a big enough deal to worry about. If you aren’t taking many supplements or don’t take things daily, it’s likely not a problem.

If you decide that you want to avoid microcrystalline cellulose, CMC, HPMC phthalate, and other excipients, you could buy whatever it is you want to supplement with as a powder. PureBulk and Bulk Supplements are two manufacturers that sell in powdered form.

Get a small digital scale* and measure out the amount you want to take. I usually then figure out which small measuring spoon approximately matches that amount, which makes it easier than always weighing out a powder. (I kind of feel like some kind of druggie when getting out my little scale and measuring powders, so a measuring spoon just makes it seem healthy instead of illicit.) *Amazon affiliate links are just suggestions - read the reviews and buy what you think is best.

If the powdered supplement doesn’t taste terrible, throw it in some yogurt, a smoothie, or whatever you’re eating/drinking. A couple of tips: There’s no disguising the taste of NAC; quercetin stains things yellow, including your teeth.

If it is something that tastes terrible, you can put it in a capsule yourself. Empty gelatin capsules are readily available, and a capsule filler tray is a relatively inexpensive way to create dozens of capsules at a time.

Alternatively, go with a brand that is already encapsulated in a gelatin capsule. For example, some of the Bulk Supplements brand capsules are gelatin, and some of the Swanson brand supplements are also in gelatin. (Please drop in the comments any other brands that you regularly find in gelatin capsules!)

Finally, the obvious alternative to some supplements is just to get the nutrient from a healthy diet.