Activated carbon

This post is about two clinical trials using oral activated carbon. The colonic delivery activated carbon seems to allow oral antibiotics to be absorbed by the small intestine, yet chelates them in the colon. [1] Non protected activated carbon prevents absorption of calcium and phosphate. [2] There may be many things that we consume or get secreted in our bile that might be messing up our microbiome that can be removed by activated carbon. It might be best we use a colonic delivery formulation like DAV132

Because not all oral antibiotics are absorbed...

Those that are may be excreted into the upper small intestine in the bile claim de Grunzber and coauthors.  [1] The additional concern was what happens to the colonic microbiome when these antibiotics reach it.  The authors cited literature suggesting diarrhea, Clostridium difficile infection (CDI), and selection of antibiotic-resistant microorganisms.  According to the authors, CDI may also be linked to obesity and allergies. [1] So how does one stay on life saving antibiotics without compromising one’s healthy microbiome? Here are the basics of the study population

• Male and female healthy volunteers >18 years old
• body mass index <30 kg/m²
• normal digestive transit and healthy
• Subjects carrying C. difficile at screening or with a history of hospitalization or antibiotic exposure (both past 3 months) or vaccination (past 28 days) were not included.
  
• randomized to receive either MXF alone (n = 14), MXF + DAV132 (n= 14), DAV132 alone (n = 8), or CTL (n = 8)
• Moxifloxacin 400 mg was administered orally, once a day (after breakfast) from day 1 to day 5 under direct observed therapy.
• DAV132 or CTL, 7.5 g, was administered orally, thrice daily (before meals) from day 1 to day 7; on day 1, the first DAV132 dose was given 2 hours before MXF. Morning administrations of DAV132 and of CTL were performed under direct observed therapy, while noon and evening intake were reported
  by the subjects.
• Compliance was assessed by counting empty bottles each following day. Follow-up was until day 37.

Figure 2 illustratesDAV132 is preserving the plasma MXT while almost eliminating the fecal load of this antibiotic.  Note that the blue inset in 2A is a magnification of the trace almost at baseline of the parent graph.  

Changes oin microbiome composition with time were assessed by computing, for each individual, the Spearman rank correlation coefficient of the relative abundance of bacterial genes between each time point and the screening pretreatment day.  If the value on day 5 is close to that at the beginning of the study, the Spearman coefficient will be high.

The problem with de Grunzman 2018 is that they just did not give good background on the genomics techniques that they used. Panel 4B is pretty simple: The more antiboiotic, the less the number of genes from the microbiome.

The figure legend of Figure 5 probably contained a misprint and required going to the text for explanation.  “Taxonomical characterization at the genus level (Figure 5) showed that Alistipes, Bilophila, Butyciromonas, Coprobacillus, Fecalibacterium, Odoribacter, Oscillibacter, Parasutterella, Roseburia, and Sutterella genera were decreased in MXF-treated volunteers, and partially (Bilophila) or fully (all others) protected by DAV132. In contrast, Bacteroides, Paraprevotella, and Lachnoclostridium were unaffected by MXF as well as MXF + DAV132 treatments.”  Part of this figure is a zoom in to illustrate that red means decrease.  A deeper hue red means a larger decrease in the numbers of the genus.  The image on the right is a zoom out that allows for a birds’ eye view of increases and decreases even if the exact phylogenetic classification has been removed.  It is interesting to note that there are differences between the control and DAV132. 

We now transition from allowing antibiotics to be absorbed by the small intestine and detoxified by the time they get to the colon to preventing small intestine absorption of phosphate and calcium.

Chronic kidney disease chelation therapy

Abnormalities in serum phosphate/calcium and vascular calcification are just a few of the symptoms of chronic kidney disease (CKD) that Gao and coworkers wished to remedy. [2] Oral calcium and phosphate chelators are not that plentiful in China. The authors wished to find something inexpensive that would work with the CKD standard of care. [2]

OAC seemed to help stabilize serum calcium and phosphate during the first part of the study.  . In the first phase of the experiment, there was a statistically significant difference in the proportion of patients with hyperphosphatemia between the OAC and placebo groups (28.57% vs. 79.17%, X² = 24.958, P = 0.000). 

Then patients were randomly divided into three groups:

1. the oral activated charcoal (OAC) group, 3x per day
2. the calcium carbonate (CC) group When serum calcium was less than 8.4 mg/dl, calcium carbonate was given. When necessary, active vitamin D was given at the same time, to maintain blood calcium levels between 8.4 and 9.6 mg/dl
3. the lanthanum carbonate (LC) group…according to the Kidney Disease: Improving Global

One minus cum survival was never defined in the text. Some censored data was presented in survival curve graph legends but the traces were not visible. “Censored” was never defined.

Finally, these graphs from Figures 5-8 of Gao 2018 show activated carbon can reduce coronary calcification score.

the differences in coronary calcification score (CACS) between the

• OAC group,525.5 ± 104.2
• CC group 688.1 ± 183.7
• LC group, 431.4 ± 122.5

were statistically significant at p<0.01. Gao and coauthors concluded that oral activated carbon delays hyperphosphatemia and coronary calcification seen in chronic kidney disease. [2]

But Wait!

What about those already at risk for osteoporosis or growing children? Do either of these groups want to risk bone loss or slowed bone development? Phosphate and calcium are main components of the bone mineral hydroxyapatite.

References

1. de Gunzburg J, Ghozlane A, Ducher A, Le Chatelier E, Duval X, Ruppé E, Armand-Lefevre L, Sablier-Gallis F, Burdet C, Alavoine L, Chachaty E, Augustin V, Varastet M, Levenez F, Kennedy S, Pons N, Mentré F, Andremont A.(2018) Protection of the Human Gut Microbiome From Antibiotics. J Infect Dis. 2018 Jan 30;217(4):628-636. PMC free article
2. Gao Y, Wang G, Li Y, Lv C, Wang Z. (2018) Effects of oral activated charcoal on hyperphosphatemia and vascular calcification in Chinese patients with stage 3-4 chronic kidney disease. J Nephrol. 2019 Apr;32(2):265-272. PMC free article