New Evidence of Synergism Between Vitamins A and D — Can They Cure Diabetes?

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Posted by: Christopher Masterjohn in WAPF Blog on 06/03/10

In 2008, researchers discovered that adult mice harbor pancreatic stem cells. When the mice suffered pancreatic injury, they would make a chemical called "neurogenin-3" that made these stem cells turn into fully functional insulin-producing beta-cells, the kind of cells that are damaged in type 1 diabetes. This led researchers to consider the possibility that we might be able to treat type 1 diabetes not only with pancreatic stem cell transplants but more simply by providing humans with factors that will "turn on" the stem cells and make them convert into new insulin-producing cells.

What types of factors might do this?

Good ol' vitamins A and D!

Chinese researchers from Hong Kong recently published a paper in Stem Cell Reviews and Reports (see abstract below) showing that vitamins A and D cooperate with one another to turn on neurogenin-3 in human pancreatic stem cells. They also provided a new mechanism for vitamin A and D interactions: they found that each vitamin increased the production of the other's receptor!

What's more, they even provided a brief defense of cod liver oil at the end of their article, and cited my 2009 article "The Cod Liver Oil Debate: Science Validates the Benefits of Our Number One Superfood."

The researchers were not trying to develop nutritional therapies to cure or treat type 1 diabetes. Instead, they were trying to develop strategies to make stem cell therapy a reality. They obtained human fetal stem cells by a procedure approved by their Clinical Research Ethics Committee. Unfortunately, many of us will still harbor ethical discomforts with this procedure; nevertheless, if humans do in fact possess pancreatic stem cells into adulthood like mice do, the discoveries may provide us with the hope of preventing, treating, or even curing type 1 diabetes without the use of fetal tissue.

As we see in this first figure, neither vitamin A nor vitamin D turned on the cell's "neurogenin-3" switch when provided alone, but when provided together they caused a dramatic increase in this pancreatic regeneration molecule.

The second and third columns show vitamins A and D provided alone. Neurogenin did not increase over the control. The fourth column shows the vitamins provided together: neurogenin increased dramatically.

Figure 7b from Ng et al., Stem Cell Rev and Rep, 2010, Epub ahead of print, March 31, 2010.

Stem cells can either use their energy to reproduce or to turn into fully functional cells. When either vitamin was provided by itself, the stem cells started reproducing; the above graph showing that the neurogenin "switch" was turned on suggests that when the vitamins were provided together, the stem cells instead began turning into functional insulin-producing cells, or at least that they began laying the biochemical groundwork for this conversion to take place.

In the next figure, we see a remarkable new piece of information: each vitamin stimulates the production of its partner's receptor!


Figure 6a and 6b from Ng et al., Stem Cell Rev and Rep, 2010, Epub ahead of print, March 31, 2010.

The control, treated with neither vitamin, is on the left. The cells treated with vitamin A are shown in the middle and those treated with vitamin D are shown in the right. In the top picture we see the effect on vitamin A's receptor, and in the bottom picture we see the effect on vitamin D's receptor. Unsurprisingly, each vitamin stimulated the production of its own receptor. Remarkably, however, vitamin D caused a 3-fold increase in the production of vitamin A's recpetor and vitamin A caused a 3-fold increase in vitamin D's receptor!

Why would the vitamin D receptor be specifically regulated by vitamin A and why would vitamin A's receptor be specifically regulated by vitamin D if these two vitamins were not intended to function in a cooperative fashion? These results provide new evidence that vitamins A and D are not enemies but are in fact, to anthropomorphize them in a fun way, eternal soul mates.

The authors concluded that if it were confirmed that the increased neurogenin seen with the combined vitamin treatment reflects an increased conversion of stem cells to functional insulin-producing cells, "this would imply that the policy of giving vitamin D supplement alone in pregnancy instead of cod liver oil would need adjustment. Cod-liver oil, as natural supplement of vitamin A and vitamin D, is well known for its beneficial effects on the growth of infants and children 45-49."

Reference 45 is my Wise Traditions article, "The Cod Liver Oil Debate: Science Validates the Benefits of Our Number One Superfood." References 46-49 are four experimental studies conducted between 1937 and 1985 that I have cited in my articles showing that vitamins A and D protect against each other's toxicity.

This paper provides powerful new experimental evidence that vitamins A and D cooperate with one another as a synergistic pair, and provides a further example showing that the Weston A. Price Foundation's work is being slowly acknowledged by the scientific community and incorporated into scientific research.
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Paper referenced above

Vitamin D and vitamin A receptor expression and the proliferative effects of ligand activation of these receptors on the development of pancreatic progenitor cells derived from human fetal pancreas.

Stem Cell Rev. 2011 Mar;7(1):53-63.
Ng KY, Ma MT, Leung KK, Leung PS.
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.

The growth and development of pancreatic islet cells are regulated by various morphogens. Vitamin A modulates in vitro differentiation of islet cells and vitamin D affects beta-cell insulin secretion, while both vitamin ligands act through heterodimerization with the retinoid X receptor (RXR). However, their effects in modulating pancreatic development have not been determined. In this study, cultured human pancreatic progenitor cells (PPCs) isolated from human fetal pancreas were stimulated to differentiate into islet-like cell clusters (ICCs). RT-PCR, Western blotting and immunocytochemistry were used to examine the expression and localization of vitamin D receptor (VDR), retinoic acid receptor (RAR), and RXR in PPCs. The effects of added all-trans retinoic acid (atRA, a form of vitamin A), calcitriol (activated vitamin D) and of these ligands together on PPC cell viability, proliferation and apoptosis were assessed by MTT, BrdU and ELISA assays, respectively. Post-treatment neurogenin-3 (NGN3) expression, necessary for islet-cell lineage development, was examined by real-time RT-PCR. Results showed that RAR, RXR and VDR were expressed in PPCs. RAR and RXR were localized in nuclei, and the VDR in nuclei, cytoplasm and plasma membrane. atRA and calcitriol each increased PPC viability and proliferation; atRA additionally decreased PPC apoptosis. Co-addition of atRA and calcitriol had no additive effects on cell viability but did increase ngn3 responses. In conclusion, RAR, RXR and VDR are expressed in human fetal PPCs and PPC proliferation can be promoted by calcitriol, atRA or both together, data valuable for elucidating mechanisms underlying islet development and for developing clinical islet transplantation.

PMID: 20354914

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See also VitaminDWiki

• Masterjohn on relationships between Vitamin A D and K – Dec 2010
• Price and Masterjohn on Vitamin A Vitamin D and Vitamin K – 2010
• Hypothesis – anticancer benefits from synergy of omega-3 and vitamin D – May 2011
• Vitamin D needs some vitamin A, but not too much
• All items in category Vitamin A 67 items