Vitamin A and the gut immune system

[Guest guest]

Dear All;

This review:

Regulation of FoxP3+ Regulatory T Cells and Th17 Cells by Retinoids

Chang H. Kim

Clin Dev Immunol. 2008: 416910 (2008)

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2278288

does a nice job of explaining the importance of vitamin A (in

particular the vitamin A metabolite, retinoic acid) in regulating the

immune system of the gut/intestines. Retinoic acid affects the

balance between anti-inflammatory regulatory T cells (Tregs), and the

newly discovered pro-inflammatory Th17 cells. Retinoic acid also

affects epithelial barrier functions, the production of IgA in the

gut (required to keep gut bacteria in check), and affects the gut-

homing properties of T cells. In the absence of vitamin A (and

retinoic acid), the gut becomes leaky, IgA synthesis is impaired, T

cells are switched from an anti-inflammatory to a pro-inflammatory

state, and the T cells do not " home " properly and end up going to

extra-intestinal sites (they have the wrong zip code!). I'm convinced

that this could be a major factor in IBD and PSC, and that's why I'll

be talking about " Thoughts on Vitamin A, IBD and PSC " at the

conference.

It's very intersting that the author of this paper is from Purdue

University. I'll make an appointment to see him ASAP.

We also saw the relevance of vitamin A to liver disease in the

article posted earlier this week, showing that collagen synthesis in

the liver can be blocked by using vitamin A-coated liposomes

containing a specific inhibitor of collagen synthesis. This looks

like a promising strategy to be able to stop and even reverse liver

fibrosis.

Another article that caught my attention this week was this one:

Chang SC, Rashid A, Gao YT, Andreotti G, Shen MC, Wang BS, Han TQ,

Zhang BH, Sakoda LC, Leitzmann MF, Chen BE, Rosenberg P, Chen J,

Chanock S, Hsing AW (2008) Polymorphism of genes related to insulin

sensitivity and the risk of biliary tract cancer and biliary stone: a

population-based case-control study in Shanghai, China.

Carcinogenesis. Mar 28 [Epub ahead of print].

http://www.ncbi.nlm.nih.gov/pubmed/18375961

This article shows that a polymorphism in one of the retinoid

receptors (RXR- is associated with bile-duct cancer, particularly

in men. This would be worth looking at in PSC because of the high

risk of bile-duct cancer in PSC patients. RXR-B is located in the

major histocompatibility complex where some of the PSC susceptibility

genes are known to be located. I'll be sure to talk with Dr.

Karlsen at the conference about this.

I desperately want to find an answer to PSC, and vitamin A (retinoid)

metabolism is providing some promising leads at the moment.

Best regards,

Dave

(father of (22); PSC 07/03; UC 08/03)

[Guest guest]

Hi Genevieve;

Definitely do talk with your hep about this! As I understand it, vitamin A deficiency is the most common vitamin deficiency in PSC:

nsen RA, Lindor KD, Sartin JS, LaRusso NF, Wiesner RH 1995 Serum lipid and fat-soluble vitamin levels in primary sclerosing cholangitis. J. Clin. Gastroenterol. 20: 215-219. http://www.ncbi.nlm.nih.gov/pubmed/7797830

and they recommend:

"Patients with PSC, especially with advanced liver disease, should be screened for fat-soluble vitamin deficiencies and supplemented accordingly"

The following article decribes how to treat vitamin A deficiency in PSC:

http://www.healthsystem.virginia.edu/internet/digestive-health/nutritionarticles/april2006.pdf

They suggest ... "If vitamin A levels are found to be low in patients with PBC/PSC, cautious replacements with lower doses (5,000–10,000 units once or twice a week) and periodic determination of serum vitamin A levels, may be a prudent approach. Vitamin A hepatotoxicity is a concern in persons with underlying liver disease."

In general, beta-carotene supplements will have less potential for toxicity because the enzyme that converts beta-carotene to retinaldehyde is feedback inhibited by retinoic acid, so there is less danger of over-production of retinoic acid when beta-carotene is supplied versus vitamin A itself (retinol).

Your hepatologist would be the best person to consult about this!

Best regards,

Dave

(father of (22), PSC 07/03; UC 08/03)

>> Dave,> > I've been thinking about a Vitamin A supplement recently, and it's on > the (ever-growing!) list of questions for my hep when I see him in 3 > weeks. My concern is, with wanting to get pregnant again soon, that I > need to be careful about how I ingest the A. Do you think a beta-> carotene supplement would also have the same beneficial effects?> > Genevieve> UC 1983, J-Pouch 1999, PSC 12/07