2.5x more all-trans-retinoic acid in chow reverse diet induced weight gain
In their manuscript that has been published online in advance, Tsuchiya et al. followed up on the results of a previous trial, in which genetically modified mice with almost no functioning vitamin A receptors showed a profound decrease in hepatic insulin-like growth factor-1 production and profound hepatic steatosis (fatty liver) - a pathology the scientists ascribed to profound insulin resistance as a direct consequence of the lack of vitamin A signaling. In their latest study, that was financed with a national research grant, and is soon to be published in the international journal Hepatology (Tsuchiya. 2012), Tsuchiya et al. fed C57BL/6J mice, which had been pre-fattened on the same high-fat, high-fructose diet many of our fellow human beings are indulging these days, diets containing either standard amount of vitamin A or 50mg of all-trans-retinoic acid per kg of chow.
|Figure 1: Body weight (left) and glucose and insulin management (right) in normal and diabetes and obesity prone mice receiving control diet, standard high fat high fructose diet (HFHFr) or HFHFr + 50mg all-trans-retinoic acid (ATRA); data in the right is expressed relative to non-supplemented control (data calculated based on Tsuchiya. 2012)|
The all-trans-retinoic acid (ATRA) <> leptin connection
And although the aforementioned results are certainly impressive, this is not an essentially novel finding - what was yet observed for the fist time in this study, is the reversal of the diet-induced reduction of hepatic leptin receptor expression in the HFHFr group receiving additional all-trans-retinoic acid in their diets (cf. figure 2, left).
|Figure 2: Effects of additional ATRA in diet on leptin receptor expression (left) and relative diet- and diet + supplementation induced changes in selected makers of non-alcoholic fatty liver disease (right; data adapted / calculated based on Tsuchiya. 2012)|
Vitamin(s) A - obesity and beyond
These still "incompletely understood" (Bonet. 2011) metabolic effects of 'real' vitamin A and its metabolites are yet only the tip of an iceberg of the largely ignored health effects of the first micronutrient in the vitamin alphabet. Other only partly related effects are
- a coordinating / controlling effect of the enzyme that converts dietary vitamin A into the active form (ATRA) on lipid metabolism (Kiefer. 2012)
- a genetic blockade of adipocyte growth and thusly a direct inhibitory effect on die-induced obesity (Berry. 2012)
- a facilitative role in the maturation and replenishment of muscle progenitor cells (Ryan. 2011)
- an ability to prime pluripotent stem cells to become myocytes (muscle cells; Le May. 2011)
- anti-cancer effects (Streb. 2011; Siddikuzzaman. 2011)
- the repair of damaged heart muscle (Kikuchi. 2011; Freire. 2011)
- protective effects on cardio-myocytes against damage due to hyperglycemia (Guleria. 2011)
- systemic anti-inflammatory and immune regulatory effects via inhibition of interferon-gamma, TNF-alpha, NF-kappa-beta, IL-12, and promoting "an anti-inflammatory environment and adequate Th1:Th2 ratios" (Garcia. 2012)
- more general metabolic functions and immune-specific+ obesity-specific deficiency effects are summarized in table 1 (Garcia. 2012)
|Table 1: Vitamin A functions, major roles in the immune system and effects of vitamin A deficiency in undernutrition and obesity (Th1, T-helper type 1 response; Th2, T-helper type 2 response; UCP, uncoupling protein; BAT, brown adipose tissue; directly adapted from Garcia. 2012)|
How much vitamin A and where do you get it from?
If we let ourselves be guided by the 2.5x amount of the standard dose (which was what the mice were actually fed), take the RDA as a reference for the latter and assume that the conversion of dietary vitamin A to all-trans-retinoic acid works properly, the corresponding human doses do actually seem pretty reasonable, with 11,250IU for men and 8,750IU for non-pregnant women and can in fact be achieved relatively easily by eating, e.g.
- 25g chicken or pig liver or 30g of beef liver
- 100g butter + 300g cream + 300g cheddar cheese
- 200g of bluefin tuna + 3 eggs + tbsp of cod liver oil
|Image 2: I don't know if you realize this, but all the good sources of vitamin D in this illustration also contain significant (measured in IU mostly way more) vitamin A.|