This is just a data-dump from my various notes files that I'd once planned to make into an article (back when I thought I might have something meaningful to say on hypromellose / hydroxypropyl methylcellulose). I'm putting it up because a couple people have asked about it, but don't expect it to make sense, or be useful in any way :)

Hypromellose is a controversial excipient used in supplements, most often to make "veggie" capsules. Many in the alternative health world caution against its consumption, such as Andrew Lessman's in The Truth about Vegetarian Capsules and Dr. Rivkah Roth's in "Veggie" Capsules May Be Far From "Natural". But what is it, and is it really a cause for concern?

##Identifying hypromellose in supplements

  1. Hypromellose may be called hydroxypropyl methylcellulose, HPMC, hypromellosum, or carbohydrate gum.
  2. Hypromellose may be used to make up "vegetable capsules" or "vegetarian capsules." This is often done without explicitly listing it on the ingredients. I've confirmed this with several companies.
  3. It may be referred to by the E number E464.

##Similar substances go through modified cellulosics, ethyl hydroxyethyl cellulose, methyl ethyl cellulose. ethyl cellulose.

Studies supporting the safety of ingesting HPMC at reasonable dosages

Since HPMC is indigestible fiber (@@),

GRAS stuff

Animal studies

General

  1. Dow Chemical's [GRAS notification with the FDAgras0213 (PDF) cites an unpublished report by the Cosmetic, Toiletry & Fragrance Association entitled "Acute oral rat study on HPMC" where the LD50 values in rats was greater than 1g/kg/day.

  2. Dow also cites "Chronic oral toxicity of a high gel point methyl cellulose (Methocel HG) in rats and dogs" (abstract here), which concludes, "given orally, even in large amounts over extended periods, Methocel HG [an HPMC substance] is singularly free from toxic properties." That conclusion is based on their experiments showing:

    • Fasted rats had an LD50 value greater than 4000mg/kg/day.
    • Rats fed differing doses of HPMC for 30 days only encountered problems at very high dosages.
    • Rats fed fed very large doses of HPMC for a year had some retardation in growth, but normal rates of death.
    • Rats fed differing doses of HPMC for 2 years had some retardation of growth at high doses, with no indication that death rates, urine sugar/protein, organ weights, and histological parameters were affected by the HPMC. However, there was a "small decrease in red blood cell counts and hemoglobin values, probably of nutritional origin" in the highest-dosage group.
    • Rabbits fed varying doses of HPMC for 30 days didn't encounter any negative effects, other than decreased weight gain in the highest-dosage group.
    • Two dogs were fed high doses of HPMC for 30 days. The dog at the highest dosage had some diarrhea, weight loss, and a fall in red blood cell count, while the slightly lower-dosage dog had no problems.

    • Two dogs fed varying doses, some as high as 3000mg/kg/day of HPMC for a year encountered no negative effects.

      I find the reporting in the Dow report a little disingenuous on the dog experiments. It summarizes the latter result as "administration of up to 3000 mg/kg/day of the same test material to dogs for a year produced no observable effects," which glosses over the varying doses and the limitations of using only two dogs.

  3. A 121-day study found no negative health effects in rats fed reasonable dosages of HPMC for 121 days. Rats did frequently die with a diet of 30% HPMC.
  4. An 84-90 day study only found negative health effects at higher doses of HPMC.
  5. A 30-day study found no negative health effects in rabbits given high doses of HPMC. When large amounts of HPMC was also given to dogs, with the only negative effects being diarrhea and decreased body weights.
  6. A 90-day study found no chromosomal aberrations in rats ingesting a diet of 5% HPMC.

Varying viscosities

  1. A 90-91 day study found no negative health effects feeding low-viscosity HPMC to rats.
  2. A 3-month study gave rats low-viscosity HPMC and found only mild health effects, and only at the highest dosage.

Rat and mouse studies

Human studies

Stuff

Rats, dogs, rabbits

@@maybe include its functional analogs as well

aka hypromellosum.

HPMC is manufactured using "pulp (cellulose), methyl chloride, propylene oxide, caustic soda solutino, acid, buffering agent, and water" (p9 FDA thing). "No raw materials from animal sources are used."

"HPMC has a polymeric backbone of cellulose, a natural carbohydrate that contains a basic repeating structure of anhydroglucose units. During the manufacture of HPMC, cellulose fibers are heated with a caustic solution, which in turn is treated with methyl chloride and propylene oxide. The fibrous reaction product is purified and ground to a fine, uniform powder." p10 FDA

hmm: can be fermented in the large intestine

anti: http://www.greenmedinfo.com/blog/veggie-capsules-may-be-far-natural

Hydroxypropyl methylcellulose has been used as an ingestible additive since the early 1950's. In supplements, it may be used for time-release purposes, or as a binder or coating agent [@@for easier swallowing]. "Hydroxypropyl Cellulose is a cousin to Methyl Cellulose that does not form a gel"