helvella - Lactose, Lactase and Hypothyroidism

 This page is very much an early draft

 

One of the issues that is frequently reported in relation to taking levothyroxine is some level of lactose intolerance.

Even people who have always consumed dairy products with significant lactose content, and often several other medicines made with lactose, seem quite often to have problems.

Apart from the general digestive tract issues usually reported in lactose intolerance, reaction to lactose can specifically result in impaired absorption of levothyroxine.

Although lactose-free formulations of levothyroxine are more widely available now than in the past, the majority of levothyroxine tablets are made with lactose. Also, some non-lactose formulations, seemingly those made with mannitol instead, cause another series of issues including stomach pain.

The obvious question is to ask what is different about levothyroxine in relation to lactose?
Several observations indicate possible ways in which levothyroxine could affect lactose digestion. All point in the direction of the lactase enzyme. The lactase enzyme (more completely, lactase phlorizin hydrolase (LPH)) might be affected at several points.

1               Levothyroxine affects the creation of lactase (at least, in rats). A hypothyroid suckling rat produces a different form of lactase which might be less active, or even inactive. It is unclear whether a similar issue can occur in adults – rat or human.

2               Lactase is formed in the brush border membrane (BBM). Anything which affects the BBM is likely to reduce the capacity to produce lactase. Many issues reduce the capacity of the BBM including Coeliac Disease.

3               Production of lactase appears to require a final step which involves enzymatic removal of a part of the molecule. Pancreatic enzymes, probably trypsin do this.

4               Trypsinogen is formed in the pancreas; pancreatic insufficiency can occur in hypothyroidism which would reduce the amount of trypsinogen produced.

5               Trypsinogen is converted to trypsin in the stomach. This requires sufficient acidity. Many who are hypothyroid have low, or no stomach acid which would affect this step.

6               Failure to supply sufficient trypsin, at the right part of the intestine, could mean that lactase fails to be made active.

Although some levothyroxine from our bloodstream does eventually end up in the intestines even in healthy subjects, the amount present from an oral dose is going to be far higher than would occur in other circumstances. Levels of levothyroxine when receiving oral doses are far, far higher than would occur in anyone not taking them.

References
 
Elferink, H., Bruekers, J.P.J., Veeneman, G.H. et al. A comprehensive overview of substrate specificity of glycoside hydrolases and transporters in the small intestine. Cell. Mol. Life Sci. 77, 4799–4826 (2020). https://doi.org/10.1007/s00018-020-03564-1

https://link.springer.com/article/10.1007/s00018-020-03564-1#citeas

Zecca L, Mesonero JE, Stutz A, Poirée JC, Giudicelli J, Cursio R, Gloor SM, Semenza G. Intestinal lactase-phlorizin hydrolase (LPH): the two catalytic sites; the role of the pancreas in pro-LPH maturation. FEBS Lett. 1998 Sep 18;435(2-3):225-8. doi: 10.1016/s0014-5793(98)01076-x. PMID: 9762914.

https://pubmed.ncbi.nlm.nih.gov/9762914/

Freund JN, Foltzer-Jourdainne C, Duluc I, Galluser M, Gosse F, Raul F. Rat lactase activity and mRNA expression in relation to the thyroid and corticoid status. Cell Mol Biol. 1991;37(4):463-6. PMID: 1934018.

https://pubmed.ncbi.nlm.nih.gov/1934018/

Hewitt JE, Smith MW. Thyroid hormone effects on lactase expression by rat enterocytes. J Physiol. 1986 Jul;376:253-65. doi: 10.1113/jphysiol.1986.sp016152. PMID: 3098965; PMCID: PMC1182797.

https://pubmed.ncbi.nlm.nih.gov/3098965/

Liu T, Reisenauer AM, Castillo RO. Ontogeny of intestinal lactase: posttranslational regulation by thyroxine. Am J Physiol. 1992 Oct;263(4 Pt 1):G538-43. doi: 10.1152/ajpgi.1992.263.4.G538. PMID: 1415712.

https://pubmed.ncbi.nlm.nih.gov/1415712/

Boyle JT, Kelly K, Krulich L, Koldovský O. Site of thyroxine-evoked decrease of jejunal lactase in the rat. Am J Physiol. 1982 Nov;243(5):G359-64. doi: 10.1152/ajpgi.1982.243.5.G359. PMID: 6814266.

https://pubmed.ncbi.nlm.nih.gov/6814266/

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A speculative discussion about why lactose might have specific issues when used in levothyroxine medicines.[/i]

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