Two new thoughts on Mineral Oil:
Although some attempts have been made at debunking mineral oil, I think all of those attempts have overlooked some important data – the actual studies done on mineral oil’s effect on the absorption of fat soluble vitamins. The studies are quite old – actually in the period just after WWII. What one study found was that mineral oil in higher quantities, consumed with the mineral oil mixed directly into the food, interfered with the absorption of Vitamin A. However at a dose of 2.5 grams per meal (twice a day) – the mineral oil had no effect on Vitamin A levels. Very nice of that study to have gone down to 2.5 grams as the dosage that was used in REDUCE-IT placebo arm was 2 grams twice daily at mealtime. Most statins are taken at bedtime, but a few timed-release statins are taken at the evening meal. As was pointed out by Mr. Lyon in his article for Seeking Alpha is that the small intestine, where nutrients and statins are both absorbed, is about 20 feet long. A small dosage of mineral oil (under 2.5 grams) cannot coat a sufficient surface of the small intestine to significantly interfere with fat-soluble vitamin uptake. This also was the finding, with the mineral mixed directly into the food and therefore getting to the small intestine simultaneously with the food. However, if we assume at least some of the REDUCE-IT participants took their medication as prescribed, the evening dose of mineral oil would precede the statin dose by 2-3 hours – the mineral oil would have passed to the large intestine, by that time. Even if some participants were “lazy” and took the statin with the evening dosage of placebo mineral oil, the dosage of 2 grams would have had a negligible effect on statin absorption. Another factor to consider is the timing of statin and mineral oil to pass from stomach to small intestine. The mineral oil was in capsules and various statins were used in REDUCE-IT. The dissolve rate of all these different pills could not have been exactly the same. So not only do we have a very small dosage of mineral oil, theoretically most of the participants should have consumed it hours before the statin dosage and even if they were taken together, time separation of uptake would have been greater than in studies where the mineral oil was mixed directly into food.
The second thought on mineral oil is one that hopefully Amarin is looking into with the trial data. While most statins are fat soluble (and therefore would likely be affected by mineral oil in large doses – 15-30 grams, sufficient to cover more of the small intestine,) two statins are water soluble and likely would have no interaction with mineral oil. Those statins are pravastatin and rosuvastatin. Of the 4000-plus participants in the placebo arm, some good percentage was likely on pravastatin. By comparing the average changes in LDL C between fat soluble and water soluble statin takers, Amarin ought to be able to further isolate any effects of mineral oil. My guess is that given the low dose of mineral oil, the group differences will be very minimal or non-existent. Such an analysis would be useful for the FDA submission. Amarin obviously has thought along similar lines as they already had looked at the RRR in placebo arm of those whose LDL C had gone down and those who had gone up. Remember that the RRR was actually better for those whose LDL C had gone up – indicating that the minor LDL C changes had no effect on the positive benefit seen by Vascepa arm. Last thought on all the fear being spread about this issue – LDL C in placebo arm went up 7 points – it was so low already that this was a 10% change. It wasn’t as if LDL C changed from 200 to 220, the average went from 77 to 84. The Vascepa side also rose from 74 to 76. What the fear mongerers fail to mention is that these LDL C levels are still in the ideal range. I have seen no convincing study that shows a significant change in CV events when LDC ranges from 76 to 84. One recent study actually had patients with LDL C in low 80s fare better than those with LDL C lowered to low 70s.
Posted to yahoo as well --- thoughts?
