Tumeric / Curcumin was identified as a common supplement that people use, in our survey of rapamycin users. A new report suggests that these supplements can harm the liver. Also note: adding black pepper / peperine to supplements and teas can increase curcumin absorption 30-fold.
One case, presented by Angeline Luong at the Kaiser Permanente Los Angeles Medical Center in California, is a 49-year-old woman with no underlying health issues who developed nausea and vomiting after taking a daily turmeric supplement, the dose recommended on the packaging, for three months.
Supplements are riskier than eating turmeric in food because they often contain additives to increase curcumin’s absorption, says Luong. For example, adding black pepper to supplements and teas can increase curcumin absorption 30-fold. Turmeric and black pepper are often used together in cooking, but this is within complex mixtures of other ingredients that limit their absorption.
Oral intake of curcumin markedly activated CYP 3A4: in vivo and ex-vivo studies
See graph below of the impact of curcumin on Everolimus (a rapamycin-like drug) levels - see the lower lines for how significantly the Curcumin lowered the blood levels of Everolimus (and so likely also rapamycin which is almost an identical molecule):
[quote=“RapAdmin, post:1, topic:3696”]
The bigger issue for rapamycin users is the impact of Tumeric / Curcumin on rapamycin blood levels. People need to be aware of how Curcumin significantly impacts the rapamycin bioavailability (greatly lowering it) - see details at bottom of this post.
Would a person not taking any curcumin for a day before and on the day that he takes his rapamycin avoid this negative effect on bioavailability if curcumin is taken on other days?
Well I feel like a dumbass… I take Longvida daily and have not paid any attention to skipping doses around my weekly rapamycin. The fact that even the lower dose seemed to markedly suppress AUC is quite striking. Strange that I definitely still seem to be absorbing a considerable amount of rapa given that my WBC count has been borderline low since starting.
Has this discussion been continued in any other threads? With a half-life of roughly 7 hours it would seem that 24-36 hours between curcumin and rapamycin would probably be enough to avoid this effect.
Someone on this site found that the half-life of rapamycin in his blood was roughly 41 hours. So it would be best to wait 24-36 hours after taking curcumin (half-life 7.5 hours) before consuming rapamycin, and then waiting roughly 3-5 half lives of rapamycin (123 to 205 hours) before taking any more curcumin. Although since the benefits from rapamycin come from alternating periods of “cleanup” and “growth” maybe you don’t have to wait 123-205 hours after consuming rapamycin - a shorter “cleanup” period may be fine.
My thoughts, as someone who takes curcurmin, are that if I take Rapamycin 2 hours before curcurmin then I should get most of the Rapamycin into my blood before the curcurmin has an effect in the intestines.
That may be wrong, however.
I have also read the above papers to get a better understanding of the liver issues. I have recently reduced my daily consumption of curcumin from 1.5g to 1g because in certain circumstances (mainly with alcohol) it appeared to cause digestion problems. I note in the papers above that if there are liver issues they are seen with high ALT over 1000 IU/L. My ALT has come down over the past year and a bit from around 20 to around 15. I have had as low as 11. My highest was 24. Hence as far as I am concerned I am going to stick to 1g per day. The papers that research overdose on this have pointed at a threshold of 1.5g/d being tolerable. I think, however, that I am going to stick to 1g.
The trouble with that approach is that it’s not curcumin per se that increases the metabolism of Rapamycin, it’s the curcumin metabolites that do so! In other words whatever curcumin is broken down into is what activates CYP4A (not bothering to look up, that might be wrong, but whatever the relevant one is), causing Rapa to be broken down more. Curcumin itself actually inhibits CYP4A so would increase absorption of Rapa, if not for its metabolites.
At least that’s my understanding from reading the papers.
So, to correctly do the analysis your are postulating, I think you need to know both the half life of Curcumin, AND the half life of whatever the relevant metabolites are, and maybe to a lesser degree the relative activation/inhibition of curcumin v its metabolite!
Plus everyone metabolizes everything differently anyway, so wtf knows?
Anyway, that’s my understanding, but I could be wrong.
I tested my Rapa blood levels and they were quite low, much lower given the dose than reported by several on this site (Thanks @Agetron ). I finally got them up with a combo of quitting curcumin (Theracumin), eating a grapefruit the night before and concurrent with dosing Rapa, as well as a big swig of olive oil. Even after all that, my (dose adjusted) blood levels are lower than most, so I’ve been taking 12 or 14 mg weekly in recent weeks, with no side effects I’m aware of.
I have been working on my plan for when I next take Rapamycin and I am getting quite confused as to the situation with Curcumin. Curcumin is argued to be an activator of CYP3a4. I have found references to it inhibiting CYP3A4. I have looked at the metabolites of Feruilic Acid and Vanillin and both of these seem to either inhibit CYP3A4 or have no effect. These are, however, supposed to be minor metabolites.
Hence I am not quite sure where the original research is that points to Curcumin activating CYP3A4.
Can anyone find the original papers or references to them.
It happens that I tend to take Ferulic Acid and vanillin separately.
Ferlic Acid is possibly a metabolite of the anthacyanins and potentially the active molecule.
The fact that the activation of cytochrome P450 3A4 or whatever might be due to the metabolites of curcumin itself, rather than curcumin, never occurred to me. Thanks.
That raises the question, “what are the half-lives of curcumin metabolites?” I found this paper:
Shaiju K. Vareed et al., “Pharmacokinetics of Curcumin Conjugate Metabolites in Healthy Human Subjects,” Cancer Epidemiol Biomarkers Prev. 2008 Jun; 17(6): 1411–1417.
The paper says “Cmax, t_sub_1/2 and AUC of total curcumin conjugates calculated from the raw data are presented in [Table 2] (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138955/table/T2/). One subject on the 10g dose level had a Tmax of 10 hr, but no curcumin conjugates were detected in this subject before 2 hr and after 48 hours of drug intake. When the Tmax was within the range of 1 to 4 hr, curcumin conjugates were completely eliminated from plasma at the 24 hr time point.”
I’ve been helped by taking Meriva, which is turmeric or curcuminoids bound to phospholipids. I wonder how long the metabolites of Meriva would last in me.
A lower dose of curcumin (0.5, 2.5 and 10 mg/kg bodyweight orally) actually inhibited CYP3A4 and increased the bioavailability of tamoxifen in rats by roughly 30-70%. http://pmid.us/22512082
This whole situation appears very complicated. It’s hard to predict what the overall effect will be. Has anyone taken a blood test while taking curcumin regularly and when taking a break from curcumin?