Some readers discovered some bugs with the Thryve upload. I believe the identified issues are fixed.

If you have done a Thryve upload in the past, you may wish to delete your old data and upload again. There was one scenario where some numbers may have been under reported in the upload.

A reader wrote about how a prescription drug effect on her varied greatly day by day. I recall that the microbiome can vary greatly day by day (from charts on http://richardsprague.com/ ). I thought I should visit this topic.

Many people know that grapefruit interacts with many drugs.

• Effect of grapefruit juice on drug metabolism in rats [1994].
• Grapefruit juice and drugs. How significant is the interaction? [1994]
• Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics of felodipine–and its potential clinical relevance [1992].
• Ingestion of grapefruit lowers elevated hematocrits in human subjects [1988].
• In vitro inhibition of midazolam and quinidine metabolism by flavonoids [1995].

Microbiome and Diet

Diet

Diet impacts the microbiome, whether the effects below are independent of the microbiome or due to temporal changes of the microbiome is unknown.

• Influence of diet and nutritional status on drug metabolism [1996].
  • ” It is well known that smoking, charcoal broiled food or cruciferous vegetables induce the metabolism of many xenobiotics, whereas grapefruit juice increases the oral bioavailability of the high clearance drugs nifedipine, nitrendipine or felodipine by inhibiting their presystemic (intestinal) elimination. Energy deficiency, and especially a low intake of protein, will cause a decrease of about 20 to 40% in phenazone and theophylline clearance and elimination of those drugs can be accelerated by a protein-rich diet. In the same way, protein deficiency induced by either vegetarian food or undernourishment will have the opposite pharmacokinetic consequences.”
• ” Feeding rats brussels sprouts or cabbage stimulates the intestinal and hepatic metabolism of drugs in animals. This effect is caused, at least in part, by certain indoles normally present in these vegetables. The feeding of a charcoal-broiled beef diet to rats stimulates the metabolism of phenacetin in vitro, and a similar diet stimulates the in vivo metabolism of phenacetin in man” [1977]
• “Several dietary factors influence the oxidative metabolism of chemicals in humans. Increasing the ratio of protein to carbohydrate or fat in the diet, feeding cabbage and brussels sprouts or feeding charcoal-broiled beef for several days stimulates human drug metabolism. The chronic ingestion of ethanol stimulates drug metabolism whereas the chronic ingestion of methylxanthine-containing foods inhibits drug metabolism. In contrast, an increase in the ratio of fat to carbohydrate in the diet of normal subjects or the fasting of obese individuals for several days has little or no effect on drug metabolism. Flavonoids in edible plants influence the metabolism of foreign chemicals by human liver in vitro. The addition of flavone, tangeretin or nobiletin to human liver microsomes activates both the hydroxylation of benzo[alpha]pyrene and the metabolism of aflatoxin B1 to mutagens. On the other hand, quercetin, kaempferol, morin and chrysin, which are also normally occurring flavonoids, inhibit the hydroxylation of benzo[alpha]pyrene by human liver microsomes.” [1980]

Microbiome

• “These data clearly illustrated that gut microbiome phenotypes significantly affected arsenic metabolic reactions, including reduction, methylation, and thiolation. These findings improve our understanding of how infectious diseases and environmental exposure interact and may also provide novel insight regarding the gut microbiome composition as a new risk factor of individual susceptibility to environmental chemicals.” [2013] – likely applies to pharmaceutical chemicals also.
• “The influence of our microbiota reaches from primary metabolites to secondary effects such as substrate competition or the activation of eukaryotic Phase I and Phase II enzymes. Further on it plays a hitherto underestimated role in drug metabolism, toxicity and pathogenesis.” [2015]
• “Metabolism by the intestinal microbiota might result in a different metabolite profile than that produced by host tissues. This could potentially result in either activation or inactivation of the pharmacological and/or toxicological actions of the compound in question. The contribution of the intestinal microbiota to drug metabolism remains relatively unexplored.” [2013]
• ” Given that the interplay between the gut microbiota and host cells is likely subject to high interindividual variability, this work has tremendous implications for our ability to predict accurately a particular drug’s pharmacokinetics and a given patient population’s response to drugs.” [2015]
• A specific example of a bacteria strain that predict cardiac drug metabolism [2017]

Bottom Line for Drug Effectiveness

If a drug has no effect on Monday, it may be effective a week or month later. The cause may be due to diet and/or microbiome (which can be influenced by diet). Welcome to the complexity of human health!

If a drug does not have the desired effect, consider a change of diet, supplements and herbs for 1-2 weeks and then try again.

2-FL (Human Milk Oligosaccharides) is a medical food which I wrote about in this August 2018 post. A reader ask for my thoughts on Enteragam, another prescription medical food. It’s Serum-derived bovine immunoglobulin/protein isolate

A general introduction to the topic of medical foods can be find in

The Emerging Therapeutic Role of Medical Foods for Gastrointestinal Disorders[2017].

• “A medical food, according to the FDA, is a food that is developed to be eaten or administered enterally under the guidance of a physician and that is meant for the specific dietary management of a condition or disease for which distinctive nutritional requirements, based upon known scientific principles, are established by medical evaluation.

Current and emergent pharmacologic treatments for irritable bowel syndrome with diarrhea: evidence-based treatment in practice[2017].

The US distributor describes is as:

“EnteraGam^® (a serum-derived bovine immunoglobulin/protein isolate, SBI) is a medical food product intended for the dietary management of chronic diarrhea and loose stools. EnteraGam^® must be administered under medical supervision. EnteraGam^® binds microbial components, such as toxic substances released by bacteria, that upset the intestinal environment. This helps prevent them from penetrating the lining of the intestine, which may contribute to chronic diarrhea and loose stools in people who have specific intestinal disorders.”

So, what is published about it?

• Clinical and Pathologic Remission of Pediatric Ulcerative Colitis with Serum-Derived Bovine Immunoglobulin Added to the Standard Treatment Regimen.[2017]
  • “SBI has been shown to induce clinical remission in adult populations and to decrease markers of inflammation in pediatric patients. ‘
• Impact of serum-derived bovine immunoglobulin/protein isolate therapy on irritable bowel syndrome and inflammatory bowel disease: a survey of patient perspective[2017].
  • ” Respondents with IBS who reported having a normal stool frequency (≤4 stools per day) increased from 35% prior to using SBI to 91% while using SBI. “
  • “A similar change toward normal stool frequency was reported by IBD respondents. “
  • “The majority of respondents agreed strongly or very strongly that SBI helped them manage their condition (66.9%) and helped them return to the activities they enjoyed (59.1%).”
• Potential mechanisms of effects of serum-derived bovine immunoglobulin/protein isolate therapy in patients with diarrhea-predominant irritable bowel syndrome.
  • “increased abundance of Proteobacteria Burkholderiales, Firmicutes Catonella, “
• Management of inflammatory bowel disease with oral serum-derived bovine immunoglobulin. [2015]
• Bovine immunoglobulin/protein isolate binds pro-inflammatory bacterial compounds and prevents immune activation in an intestinal co-culture model.[2015]

Bottom Line

. This is a promising medical food that may have implications across most of the conditions that I tend to look at. The absorption of toxins from bacteria makes it a universal treatment candidate.

If you have an opportunity to try it, I would recommend the experiment (and ideally reporting back here after 30 days).

A similar product (non-prescription)

Note: No explicit pubmed studies found on this product. It is also just one type of immunoglobulin.

SBI Protect Capsules

“The findings of the lactulose breath test in irritable bowel syndrome patients have been used to suggest that most patients have small intestinal bacterial overgrowth (SIBO), and this association has spawned the widespread use of antibiotics in IBS. The study by Bratten and colleagues demonstrates that this test does not discriminate between IBS patients and healthy controls when criteria from recent clinical IBS studies are applied. ” [2008]

I recently added some more studies and found that the list of bacteria that will consume lactulose is quite large — with both good and bad listed.

Bottom Line

Recently I posted about another probiotic that gave positive lactulose breath test when given to healthy individuals. I look at the list above and see many bacteria that are often in yogurt or available as probiotics.

In short, not only have studies on human discredited this test — but logic also discredit it. It is totally unclear which bacteria is overgrown!

This is a continuation of my trying to get caught up on reviewing interesting news. Sometimes a new dimension appears that results in enhancements of the analysis site; other times, it is just interesting events happening. The quality of the items can be questionable (marketing literature), often the reviews reveal some interesting gems.

• Gigantic study of Chinese babies yields slew of health data
  “The Chinese team has so far avoided similar problems. Its rich collection of 1.6 million biological samples includes specimens of stools, blood, placental tissue and umbilical cords. Extensive surveys also record participants’ eating habits, mental health, and other lifestyle factors, such as the amount of mould in their house.”
• “Gut microbiota modulate neurobehavior through changes in brain insulin sensitivity and metabolism”[src]
• ‘Social microbes’ critical to brain development…Absence linked to reduced sociability in people with autism spectrum disorders”[src]
• From src
  
• 
• 
• 
• Designing large-scale gut microbiome studies – 10 essential considerations<http://blog.dnagenotek.com/microbiome/designing-large-scale-gut-microbiome-studies-10-essential-considerations>
• An analysis of faecal metabolites (chemical molecules in stool produced by microbes) found that less than a fifth (17.9 per cent) of gut processes could be attributed to hereditary factors, but 67.7 per cent of gut activity was found to be influenced by environmental factors, mainly a person’s regular diet. [src]
• Triclosan (TCS) is a high-volume chemical used as an antimicrobial ingredient in more than 2000 consumer products, such as toothpaste, cosmetics, kitchenware, and toys. We report that brief exposure to TCS, at relatively low doses, causes low-grade colonic inflammation, increases colitis, and exacerbates colitis-associated colon cancer in mice. Exposure to TCS alters gut microbiota [src]
  • “Triclosan exposure is practically unavoidable in the United States, but little is known how ingestion may affect our health” [src]

  • Why Is Triclosan in Toothpaste? [Consumer Reports]

• Bacteria Survive in NASA’s Clean Rooms by Eating Cleaning Products [src]
• When three groups of mice received a custom diet supplemented with porphyrin-rich seaweed (a kind of microbiota-accessible carbohydrate (MAC) found in nori) seven days after inoculation with B. ovatus NB001, a robust increase of up to six orders of magnitude was detected in the strain’s density in feces, irrespective of background microbiota.  [src]
• As reported on November 17, 2017 a randomized, double-blind, placebo-controlled study in 90 older women showed that supplementation of the probiotic strain Lactobacillus reuteri ATCC PTA 6475 decreased bone loss compared to placebo [src]
• Daily supplementation with the probiotic strain Bacillus subtilis C-3102 may improve stool frequency and consistency in healthy people, says a new study. [src] always note the “may” is not a “will”/ Speculation
• Researchers from Japan are using the findings of studies on centenarians in the country to try and produce new products that will replicate the beneficial aspects of their microbiota. [src]
• Here we report that our routine use of mock communities as internal standards allowed us to discover highly aberrant and strong biases in the relative proportions of multiple taxa in a single Illumina HiSeqPE250 run. [src]
• No clear evidence probiotics can help with human anxiety, study finds
• The University of Otago, Christchurch, researchers found a toxic form of a bacteria called Bacteroides fragilis in the gut of almost 80 percent of people with a pre-cancerous lesion — a precursor to the disease.[src]
• Dr Costello led a faecal microbiota transplantation (FMT) study the results of which demonstrate the ability to induce remission in UC, without significant side-effects. [src]