The Gut and Food Supplements

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The following commentary is extracted and modified from:

Regulation of Gastrointestinal Mucosal Growth.
Rao JN, Wang JY.
San Rafael (CA): Morgan & Claypool Life Sciences; 2010.


Your gastrointestinal tract is the only part of your body that directly comes in contact with a wide variety of nutrient molecules before they are absorbed. Various nutritional supplements, such as vitamins, amino acids, nucleic acids, and sugars, are shown to have trophic (promoting cellular growth, differentiation, and survival) effects on GI mucosal growth, epithelial cell proliferation, and differentiation.[1]

For some time it has been widely accepted that the amino acid glutamine plays an important role in the regulation of GI mucosal metabolic functions and growth.[2] Several studies have demonstrated that intestinal glutamine metabolism not only acts as a nutritionally important portion of the energy generation, but also as the precursor or key factor of a number of important metabolic pathways of other amino acids, especially those leading to the synthesis of ornithine, citrulline, arginine, and proline. Among all amino acids, glutamine metabolism has had a greater influence on a variety of aspects of clinical nutrition.2

There is also evidence showing that the removal of glutamine by starvation of cultured intestinal mucosal cells inhibits cell proliferation,2 whereas glutamine supplementation in rats exhibits a significant increase in the villous heights of small intestine. In contrast, the numbers of villi per unit length of bowel decrease when glutamine synthesis is inhibited by methionine sulphoximine or in the animals fed with glutamine-free diet.[3] In one study, it has been also noticed that there is a breakdown of the epithelial junctions in the glutamine-deprived and glutamine synthetase-inhibited intestines. These findings support the notion that glutamine in diet supplements is necessary for normal intestinal mucosal growth and for maintenance of the intestinal mucosal integrity. Wiren et al.[4] then demonstrated the importance of glutamine in the regulation of cell differentiation by using cultured Caco-2 and HT-29 cells.

However, there are some controversial evidences about the role of glutamine supplements in the GI mucosal growth. It has been reported that oral glutamine supplementation alone does not sufficiently induce protein synthesis in the jejunal mucosa of malnourished rats, regardless of the total food intake or the presence or absence of glutamine supplementation.[5] Recently, Shyntum et al.[6] reported that dietary sulphur amino acid supplementation stimulates ileal mucosal growth rate after massive small-bowel resection in rats. In this study, they observed that resected and sulphur amino acid supplemented rats exhibited increased ileal adaptation as indicated by the increase in full-thickness wet weight, DNA, protein content, and mucosal crypt depth and villous height. Despite this negative observation, in particular experimental condition, the trend of emerging results suggest that glutamine supplements are important for maintaining normal mucosal architecture including tight junctions.

Other important diet supplements are water- and fat-soluble vitamins which are essential for intestinal epithelial cell growth and epithelial cell proliferation .[7],[8] Among them, vitamin A and its bioactive metabolites (retinoic acid) are well characterised as important agents that modulate a variety of GI physiological functions, including mucosal growth, cell proliferation and Treg promotion. Uni et al.[9] found that vitamin A deficiency interferes with  normal growth rate in chickens. Decreased vitamin A alters the functionality of the small intestine by reducing epithelial cell proliferation and maturation. Similar findings were also observed in rats and studies have shown that vitamin A deficiency modifies the maturation and differentiation processes of the small intestinal mucosa.[10] In another study conducted in calves that were supplemented with vitamin A, villous heights in the ileum and villous height to crypt depth ratios in the jejunum are enhanced in comparison with those from control animals. In addition, vitamin D, vitamin C, and Riboflavin in diet supplements also have similar beneficial effects on GI mucosal growth and epithelial tissue homeostasis.[11]

Several studies also show the importance of dietary nucleotides in the regulation of GI mucosal growth and development. [12],[13] Exogenous supplementation of nucleotides was found to have a beneficial effect on intestinal growth after parenteral supplementation. The wet weight of the jejunal mucosa and content of total protein and DNA are higher in the rats supplemented with a mixture of nucleotide and nucleosides than those observed in the rats fed with parenteral solution alone. The morphometric analysis showed that there is a significant increase in the villous height after nucleic acid supplementation, supporting the notion that dietary nucleotides are also crucial for normal mucosal cell growth and functions.

Butyrate supplementation is also shown to enhance the GI mucosal growth and improve several indices of gastrointestinal biological functions in piglets after weaning.[14] In addition, various minerals, such as zinc, magnesium, and potassium, in diet supplements also affect physiological functions of the intestine and show the beneficial effects on intestinal mucosal growth.[15],[16]


Whilst by no means a fully comprehensive review, and many studies are based on animals, the impression should be clear, the foods we consume have an impact not only on the tissues inside our body, but also those on the outside – the mucosal tissues that line the gastrointestinal tract receive their nutrition at the same time as we do – it makes sense to feed our gut first, as without suitable nutrients its competence is quickly compromised.


[1] Mathers JC. Nutrient regulation of intestinal proliferation and apoptosis. Proc Nutr Soc 57: pp. 219–23, 1998. View Abstract

[2] Reeds PJ, Burrin DG. Glutamine metabolism: nutritional and clinical significance. glutamine and the bowel. J Nutr 131: pp. 2505S–8S, 2001. View Full Text

[3] Tannus AF, Darmaun D, Ribas DF, Oliveira JE, Marchini JS. Glutamine supplementation does not improve protein synthesis rate by the jejunal mucosa of the malnourished rat. Nutr Res 29: pp. 596–601, 2009.View Abstract

[4] Wiren M, Magnusson KE, Larsson J. The role of glutamine, serum and energy factors in growth of enterocyte-like cell lines. Int J Biochem Cell Biol 30: pp. 1331–6, 1998. View Abstract

[5] Tuhacek LM, Mackey AD, Li N, DeMarco VG, Stevens G, Neu J. Substitutes for glutamine in proliferation of rat intestinal epithelial cells. Nutrition 20: pp. 292–7, 2004. View Abstract

[6] Shyntum Y, Iyer SS, Tian J, Hao L, Mannery YO, Jones DP, Ziegler TR. Dietary sulfur amino acid supplementation reduces small bowel thiol/disulphide redox state and stimulates ileal mucosal growth after massive small bowel resection in rats. J Nutr 139: pp. 2272–8, 2009. View Abstract

[7] Fedriko V, Bostick RM, Flanders WD, Long Q, Sidelnikov E, Shaukat A, Daniel CR, Rutherford RE, Woodard JJ. Effects of vitamen D and calcium on proliferation and differentiation in normal colon mucosa: a randomized clinical trial. Cancer Epidemiol Biomarkers Prev 18: pp. 2933–41, 2009. View Abstract

[8] Zanoni JN, Fernandes PRV. Cell proliferation of the ileum intestinal mucosa of diabetic rats treated with ascorbic acid. Biocell 32: pp. 163–8, 2008. View Abstract

[9] Uni Z, Zaiger G, Gal-Garber O, Pines M, Rozenboim I, Reifen R. Vitamin A deficiency interferes with proliferation and maturation of cells in the chicken small intestine. Br Poult Sci 41: pp. 410–5, 2000.View Abstract

[10] Thomas S, Prabhu R, Balasubramanian KA. Retinoid metabolism in the rat small intestine. Br J Nutr 93: pp. 59–63, 2005. View Abstract

[11] Zanoni JN, Fernandes PRV. Cell proliferation of the ileum intestinal mucosa of diabetic rats treated with ascorbic acid. Biocell, 32: pp. 163–8, 2008. View Abstract

[12] Mashiko T, Nagafuchi S, Kanbe M, Obara Y, Hagawa Y, Takahashi T, Katoh K. Effects of dietary uridine 5′-monophosphate on immune responses in newborn calves. J Anim Sci 87: pp. 1042–7, 2009. View Abstract

[13] Tang Z, Yin Y, Zhang Y, Huang R, Sun Z, Li T, Chu W, Kong X, Li L, Geng M, Tu Q. Effects of dietary supplementation with an expressed fusion peptide bovine lactoferricin-lactoferrampin on performance, immune function and intestinal mucosal morphology in piglets weaned at age 21 d. Br J Nutr 101: pp. 998–1005, 2009. View Abstract

[14] Le Gall M, Gallois M, Seve B, Louveau I, Holst JJ, Oswald IP, Lalles JP, Guilloteau P. Comparative effect of orally administered sodium butyrate before or after weaning on growth and several indices of gastrointestinal biology of piglets. Br J Nutr 102: pp. 1285–96, 2009. View Abstract

[15] Jing MY, Sun JY, Weng XY, Wang JF. Effects of zinc levels on activities of gastrointestinal enzymes in growing rats. J Anim Physiol Anim Nutr (Berl) 93: pp. 606–12, 2009. View Abstract

[16] Milovic V. Polyamines in the gut lumen: bioavailability and biodistribution. Eur J Gastroenterol Hepatol 13: pp. 1021–5, 2001. View Abstract

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