Phage Therapy Supplements


This article looks at some of the more easily accessible phage therapy products. Please read the previous article Introduction To Phage Therapy (*) for a better understanding of phage therapy. In short, phages (or bacteriophages) are viruses that can attack bacterial cells. In the process phages break down bacterial cell membranes, killing the bacteria. Phages then use the cellular material to replicate. These new phages can destroy more bacterial cells. Phages may be very narrow in their selection of bacteria. If properly selected phages can target pathogenic bacterial strains or families while sparing beneficial bacteria. Phages are not subject to antibiotic resistance of the kind from conventional antibiotics.

Phage therapy is a huge area, so I narrowed down my search to the most practically available phage supplements. The results break down into a number of categories. Phage products with their phage contents listed (to a degree), phage products without phages described and phage products which include probiotic bacteria. Of the products that do list phage contents all contain the same 4 phages, and most of those list the quantity as 15mg, either as PreforPro, Tetraphage, or Prephage preparations. It may be that all these products contain the same phages in the same quantity produced by the same manufacturer (Deerland Enzyme).

Prebiotics are nutrients that feed microorganisms, like bacteria or yeast. It’s usually implied that prebiotics feed beneficial microorganisms more than pathogenic ones, allowing them to outcompete pathogenic strains. These particular phage cocktails (multiple phages in one delivery system) are often described as prebiotic, which seems strange initially as they destroy cells. However, the claim is that the dead bacteria provide nutrients for the more beneficial bacteria, and so the prebiotic effect. These phage cocktails should kill pathogenic bacteria and feed beneficial bacteria. There are some studies showing an increase in beneficial bacteria after phage use. I have been able to find very few references on this (these) phage cocktail(s).

In late 2017 there was an oral presentation given at the 58th Annual Conference of the American College of Nutrition. This study used the cocktail of phages used in all these products which list their phage contents, and I assume the ones which do not. These are LH01-Myoviridae, LL5-Siphoviridae, T4D-Myoviridae, and LL12-Myoviridae. The study was on people with mild gastrointestinal disorders. The phage treatments were successful in eliminating some pathogenic bacteria, along with altering inflammatory cytokines and cholesterol. No adverse affects were reported. This does not seem to be published yet. Many of the references I’ve found in articles that seem to relate to this phage cocktail are also unpublished.

“Purpose/Objectives: The Bacteriophage for Gastrointestinal Health (PHAGE) Study is a complex randomized, double-blind, placebo controlled cross-over trial designed to investigate the utility of four supplemental bacteriophage strains (LH01-Myoviridae, LL5-Siphoviridae, T4D-Myoviridae, and LL12-Myoviridae) to modulate the gut microbiome, and therefore ameliorate common gastrointestinal distress symptoms (e.g., gas, bloating, diarrhea, constipation, etc) experienced among healthy individuals.
Methods: 33 individuals not diagnosed with gastrointestinal disorders (e.g., Crohn’s disease, irritable bowel disease, etc) but healthy individuals who reported significant gastrointestinal distress were enrolled into the study. The PHAGE Study is designed to evaluate shifts in the microbiome using 16S rRNA sequencing, changes in localized hs- CRP, fecal calprotectin, short-chain fatty acids, and systemic changes in 12 inflammatory mediators (e.g., TNF-a, IL-6, etc), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, glucose, and metabolic safety markers (ALT, AST, etc).
Results: The bacteriophage cocktail was well tolerated, with no adverse events or differences in metabolic safety markers detected during the study. The treatment effectively modulated the microbiome, eliminating several pathogenic phyla, while improving LDL-cholesterol and some systemic inflammatory cytokines.
Conclusions: Bacteriophages seem to have a safe clinical application for eliminating problematic bacteria in the GI tract. Future studies designed to assess their lipid- lowering capacity as a primary endpoint are needed.” (*)

Floraphage

I think Floraphage was one of the first on the market, or at least early in this cycle of phage production. As I described in the previous article, phage therapy was once pretty widespread before becoming limited to a few countries for most of its history. Floraphage has a good reputation but it does not list its phages. Some retailers mention 15mg of phages in Floraphage, this is consistent with other products which do list phage contents. Any product I’ve seen that lists an amount lists 15mg and  those which also list phages list the same 4 phages. I’ve contacted Arthur Andrew Medical, producer of Floraphage, about its contents. I will post them if I get a response. *Floraphage responded that most of the phage products on the market all contain the exact same blend of phages (including Floraphage).* When I enquired about references for claims made about the product they sent me this Floraphage Laboratory Report(*). As you can see from the lab report, they claim greatly increased levels of probiotic bacteria Bifidobacterium Longum, Bifidobacterium Breve, and Lactobacillus Lactis when grown in the precence of Floraphage phages and “non beneficial” bacteria.

Bifidobacterium is particularly interesting in terms of health as it seems to lower both intestinal and circulatory levels of endotoxin/lipopolysaccharide. Endotoxin (*), particularly when it leaves the gut and circulates throughout the body, is very strongly associated with many chronic diseases, notably type II diabetes and obesity(*).

Obesogenic diets (like a high-fat diet) tend to decrease bifidobacterium, cause “leaky gut”, and increase endotoxin, leading to obesity and type II diabetes. Increasing bifidobacterium (through various methods) can reverse these processes.

“Recent evidence suggests that intestinal Bifidobacterium species (spp.) positively correlates with improved insulin resistance and obesity, and this might be linked to metabolic inflammation. The expression of intestinal REG (regenerating) family proteins which are widely involved in inflammatory bowel disease and diabetes are still unknown in metabolic syndrome. Hence, we investigated the effects of Bifidobacterium longum (BIF) supplementation on metabolic parameters, intestinal function and expression of Reg family genes in a rat model of metabolic syndrome induced by a high-fat (HF) diet. We specifically increased the gut bifidobacterial content of HF-fed rats through BIF supplementation. Compared with the normal chow-fed control rats, HF feeding significantly reduced intestinal Bifidobacterium. As expected, BIF supplementation fed rats had totally restored quantities of Bifidobacterium. HF diet-fed rats showed significant increase in body weight, fat deposits, systolic blood pressure, fasting glucose, fasting triglycerides and reduced insulin sensitivity, while increases of intestinal Bifidobacterium did improve HF-diet-induced metabolic disorders. HF feeding led to significantly higher levels of the plasma lipopolysaccharide, interleukin-1β and intestinal myeloperoxidase, as well as intestinal inflammatory activity index, while these parameters were normalized to the control levels in the HF + BIF-treated rats. The levels of RegI mRNA and protein in the HF + BIF group were significantly higher than the control and the HF groups. Increasing Bifidobacterium in the gut improved HF-fed-induced metabolic syndrome by reducing metabolic endotoxin concentrations and intestinal inflammation, as well as upgrading the expression of intestinal Reg I as a regulator of growth factor.”

see:
Microencapsulated Bifidobacterium longum subsp. infantis ATCC 15697 Favorably Modulates Gut Microbiota and Reduces Circulating Endotoxins in F344 Rats
Getting better with bifidobacteria
Gut Bifidobacteria Populations in Human Health and Aging
Lactic acid bacteria and bifidobacteria for treating endotoxemia
Potential probiotic Bifidobacterium animalis ssp. lactis 420 prevents weight gain and glucose intolerance in diet-induced obese mice
Single-species versus dual-species probiotic supplementation as an emerging therapeutic strategy for obesity
Probiotic Bifidobacterium longum NCC3001 Reduces Depression Scores and Alters Brain Activity: A Pilot Study in Patients With Irritable Bowel Syndrome.
Probiotics and Obesity
Microbial Translocation in Chronic Liver Diseases

Floraphage works out about 55 cents per capsule on Amazon.com.
Arthur Andrew Medical Floraphage
15 mg, 90 Count ($49.95)
0.55 per dose approx

Advanced-supplements sell Floraphage in the UK

Other Probiotic-Free Phage Supplements

Two products list their phages and do not contain probiotic bacteria. While probiotic bacteria can be beneficial they may also come with some risks. I’ve taken a lot of probiotics in the past but I avoid them nowadays. Their interactions are extremely complex and I think the science is in pretty early stages.

Nutrivee contains 15mg of PreforPro and costs about $0.33 per dose. This seems to be the best product on amazon given the above considerations and price.
60 count ($19.85)
PreforPro® 15mg
LH01 – Myoviridae
LL5 – Siphoviridae
T4D – Myoviridae
LL12 – Myoviridae
Rice dextrose, hypromellose, water.

Dr Tobias Ultimate Prebiotic contains the same phage cocktail (15mg of PreforPro) and works out to $0.70 per dose. The “other ingredients” are different for these two products.
30 caps ($20.87)
PreforPro® 15mg
LH01 – Myoviridae
LL5 – Siphoviridae
T4D – Myoviridae
LL12 – Myoviridae
Other ingredients: Vegetable cellulose (DRCaps®), medium chain triglycerides and tapioca dextrin

Phage Cocktails With Probiotics

Life Extension Florassist Gi With Phage Technology is one of the older products on the market. It works out to$ 0.67 per dose.
30 Caps ($20.15)
TetraPhage Blend 15 mg
LH01 – Myoviridae
LL5 – Siphorviridae
T4D – Myoviridae
LL12 – Myoviridae
Proprietary Probiotic Blend 15 Billion CFU † ** Lactobacillus acidophilus La-14; Bifidobacterium lactis Bl-04; L. paracasei Lpc-37; L. rhamnosus Lr-32; B. bifidum/lactis Bb-02; B. longum Bl-05
Other ingredients: glycerin, vegetable cellulose (capsule), microcrystalline cellulose, silica, purified water, stearic acid, chlorophyllin.
Floraphage is the only phage product currently available product on amazon uk at around £1.23 per capsule.

Fibro-Fix Probio-Fix $0.83 per dose
60 count ($49.95)
Prephage 15mg (Proprietary Phage)
Proprietary Probiotic Blend (Bifidobacterium bifidum, Lactobacillus acidophilus, Bifodobacterium longum, Lactobacillus rhamnosus, Bifodobacterium breve, Lactobacillus casei, Sterococcus thermophilus)
Tapioca dextrin, MCT, HMPC, Water, gellan gum.

Designs for Health – Probiophage DF – Dairy-Free Bacteriophage $1.00 per dose
60 caps ($59.12)
Bacteriophage formulation combining four types of phages
(as the proprietary bacteriophage blend PrePhage)
Seven strains of probiotics.
Delayed-release capsule to increase intact delivery to the small intestine by protecting these organisms from stomach acid.
Tapioca dextrin, MCT, HMPC, Gellan gum, Water.

Healthy Brook Probiotic and Prebiotic  $0.32 per dose
60 ($15.99)
PreforPro® 15mg
LH01 – Myoviridae
LL5 – Siphoviridae
T4D – Myoviridae
LL12 – Myoviridae
Probiotic Bacteria consists of: DE111 TM (Bacillus subtilis), Bacillus coagulants, Lactobacillus acidophilus, Bifidobacterium lactis
Veg Cellulose, Maltodextrin, MCT.

DownInThePark Ultra Defense (Same as Healthy Brook)  $0.56 per dose
30 count ($16.57)
PreforPro® 15mg
LH01 – Myoviridae
LL5 – Siphoviridae
T4D – Myoviridae
LL12 – Myoviridae
Probiotic Bacteria consists of: DE111 TM (Bacillus subtilis), Bacillus coagulants, Lactobacillus acidophilus, Bifidobacterium lactis
Veg Cellulose, Maltodextrin, MCT.

If anyone knows of more published data on this phage cocktail I’d be interested to see it.