Monday, July 11, 2011

Want B12, But Hate Meat? Drink Milk! SNAC-Fortified Cyanocobalamin 136% More Bioavailable Than Standard B12 - Still Less Effective Than B12 From Cow's Milk

Figure 1: Milk still rules the
world (of B12 supplements ;-)
Vitamin B12 deficiency is probably more prevalent, than many people would have it. The water-soluble vitamin is most abundant in foods of animal origin and vegetarians (let alone vegans) are as much at risk of having inadequate B12 levels, as people with achlorhydria and, consequently, low intrinsic factor (an enzyme that requires an acidic environment to function and facilitate the utilization of B12 from foodstuff), or more generalized disturbances of the gastrointestinal structure due to aging (food-cobalamin malabsorption becomes increasingly prevalent after the age of 50), gastric resection, ileal resection, Crohn's disease, and bacterial overgrowth of the intestine. With vitamin B12 deficiency affecting cell division and precipitating to megaloblastic anaemia and neuropathy, close monitoring not only of vitamin B12 intake, but also of its proper utilization is of utmost importance for people belonging to one of the aforementioned groups.

Scientists from Emisphere Technologies in Cedar Knolls, New Jersey, have now come up with a new cyanocobalamin/SNAC coformulation, in which the sodium caprylic acid salt, N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC), a proven drug delivery agent, shall facilitate a more pronounced and more reliable absorption of orally supplemented vitamin B12 (Castelli. 2011). The formula, which contained 5-mg cyanocobalamin and 100-mg SNAC was administered to 6 human subjects in the fasted state in the form of 1 tablet, which had to be taken with 50 mL of water. Blood samples were taken at staggered intervals with the last blood draw taking place 24h after the ingestion of the B12/SNAC coformulation.
Figure 1: Time to and maximal serum concentration of B12 after oral administration or infusion of cyanocobalamine with and without SNAC; note: in order to compensate for the major differences between oral cyonocobalamine with and without SNAC a logarithmic scale was used (data adapted from Castelli. 2011).
As expected the concomitant administration of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) increased the meager biovalability of cyanocobalamine (which is absorbed really poorly, anyway) significantly:
Absolute bioavailability of B12 with the SNAC formulation was calculated from non–baseline-adjusted data to be 5.09% and was signi´Čücantly greater (P < 0.05) than the commercial formulation (2.16%).
In view of the recently elucidated bioavailability of natural B12 from plain cow's milk (Matte. 2011), or should I say "liquid white gold", the 136% increase in bioavailability Christina Castelli and her coworkers achieved with their artificial combination of B12+SNAC appear quite ludicrous. 8%-10% that is the bioavailability et al. report in Jacques Matte and his colleagues from Canada report in their study on the bioavailability of vitamin B12 from cow's milk. Granted, this is a pig model, but other than rodents, which are usually used when it comes to studies, in which surgical interventions are necessary to elucidate the exact pharmacodynamics of a specific drug, pigs provide a very adequate model for the human gastrointestinal system, or as Miller and Ullrey already stated it in a 1987 paper on the "The Pig as an Animal Model For Human Nutrition" (Miller. 1987)
[...]with the possible exception of nonhuman primates, it is apparent that the omnivorous pig is one of the best models for study of nutrition issues in the omnivorous human.
This long established adequacy of the pig model of the human gastrointestinal tract has only recently been confirmed by Goulloteau et al. (Guilloteau. 2010). Matte et al.'s result that vitamin B12, which is naturally and abundantly present in cows’ milk, is more available at the intestinal level than the synthetic form - even if the latter is supplemented with SNAC - are thus very likely to apply to humans, as well.
Figure 2: Pharmacokinetics of vitamin B12 from different sources measured in pigs with an ultrasonic flow probe around the portal vein and a catheter inside the portal vein; values expressed as differences vs. unsupplemented animals; both values for cyanocobalamine alone are effectively 0, i.e not different from unsupplemented pigs (data adapted from Matte. 2011).
These results are also in accordance with retrospective studies in human subjects showing that vitamin B12 status is highly correlated with dairy product intake and studies on the absorption (absorption = entering the cells vs. bioavailability = becoming available in the blood stream) of vitamin B12 from dairy products in older men and women (>60y) by Robert M. Russel et al. (Russel. 2001), who report absorption of up to 65% for milk, which would be almost identical to the generally accepted absorption coefficient for meat products.
Note: Using a pig model Matte et al. were able to actually measure the portal-drained viscera (PDV) flux of vitamin B12, which provides more reliable results than radio-labelling studies, as they were used in Russel et al. It is thus all the more intriguing that the PDV for the unsupplemented diet or cyanocobalamin supplements [...] were not different from 0", or in other words - providing pigs with cyanocobalamine, which is the form of vitamin B12 that is used in most common dietary supplements, had no effect  on serum B12 concentrations, at all.
So, what does this tell you, after all? Well, let me phase it like that: If you have a Ferrari Enzo (milk and meat) waiting for you at the front door (in the fridge), wouldn't it be plain-out stupid to try to chip-tune (add SNAC) the family car (cyanocobalamine)? An the moral of the Story? Eat, don't supplement your vitamins!