A few years ago I wrote A Frugal List of Supplements for ME/CFS using knowledge at that time trying to rank order supplements that may help by best cost. Today a similar question came up. I am retired (72 y.o.) and working part time with a variety of complex conditions in the household so getting the right stuff at reasonable cost is a priority.

In this post I will share what our current strategies are and illustrate cost savings. For making our own capsules, I have ignored the cost (since it is low).

Example #1 Supplement Hesperidin

Choice #1: Off the shelf: 13.57 / ( 0.500 g x 60) = $0.45 per gram

Choice #2: Bulk Powder off Amazon. $16.96/ 100 grams = $0.17 /gram

Choice #3: Buying direct from a manufacturer in bulk (but certified organic): 24.14 /100 = $.24 / gram (with free shipping)

Example #2 Lactobacillus Plantarum

Choice #1: Off the shelf: 30 capsules with 10 BCFU: $12.42 / (30 x 10) = $0.04 / BCFU

Choice #2: Bulk Probiotics as powder: 169.17 / (400 x 100) = $0.004 per BCFU. Lower package sizes available at slightly higher cost per BCFU.

Choice #3: Buying direct from a manufacturer in bulk (Organic and typically manufactured within 2 weeks of shipping): $138.73 / (20 x 1000) = $0.007/BCFU. Lowest package is $0.02/BCFU

A key issue is probiotics is time since manufacture, abuse in storage (i.e. not kept is fridges in transit and storage — if you look “behind the scenes” at many health food stores, you will see boxes of probiotics just kept in the back, not refrigerated. They are then put it into the display refrigerator as needed). See Probiotics — what is advertised may not be what you get

Example #3 Herb Turmeric

Choice #1: Off the shelf: $12.49/(1 gm x 60) = $0.21 / gram

Choice #2: Bulk – from Amazon (note this is Organic, above is not): $14.99 / 907g = $0.016 / gram

Choice #3: Oversea supplier (also organic): $18.11 / 100gram = $0.18/gram

Bottom Line: Up to 90% reduction in Supplement Costs is possible

There are always other factors — for example, some probiotics may only be available from just one supplier (i.e. L. Jensenii, E. Coli Nissle 1917). Do you want it to be Organic? Degree of trust in manufacturer, supply chain handling, seller’s handling (I deemed it very unlikely that Probiotics sold by Amazon are refrigerated, more likely just sits in their warehouses until sold).

Also, be pragmatic on likely duration of use. Don’t over buy to “save money” and have it sitting on the shelf forever…

Remember: Most supplements are high profit margins. At least one supplement seller who also sells microbiome testing kits is suspected to sell their kits at below cost because of the profit from selling the supplements to the same customers.

Our own experience with Maple Life Sciences probiotics have been awesome. We see changes in stools within 48 hours when we rotate between probiotics.

A study demonstrated Fecal Microbiota Transplantation (FMT) alone can change a skinny mouse into a fat one is detailed in the research published by the journal Science. In this study, researchers transplanted gut bacteria from human twins discordant for obesity into germ-free mice. The mice that received gut bacteria from obese twins grew fat, while those that received bacteria from lean twins remained lean. This experiment provided compelling evidence that gut microbiota can influence body weight and adiposity independently of diet or other factors. Visual below of mice feed identical diet.

My own experience is loosing 30 pounds from the addition of a specific probiotic (Akkermansia) over a year without a change of diet. IMHO, a change of diet along may not do it. Often it takes two things: changing the diet AND changing the bacteria in the gut.

Literature

Probiotics that have the best actual evidence

Note that some probiotics can result in weight gain, so taking random ones is not the way to do it. Many of the studies found effective using probiotics mixtures included Lactobacillus plantarum

• Use of probiotics in preventing and treating excess weight and obesity. A systematic review “the use of probiotics in the absence of dieting produced a significant reduction in body weight and body mass index in 66.6% of the reviewed studies”
• Akkermansia muciniphila Suppresses High-Fat Diet-Induced Obesity and Related Metabolic Disorders in Beagles.
• Effects of oral Akkermansia muciniphila supplementation in healthy dogs following antimicrobial administration.
• Akkermansia and Microbial Degradation of Mucus in Cats and Dogs: Implications to the Growing Worldwide Epidemic of Pet Obesity.
• The Role of Lactobacillus plantarum in Reducing Obesity and Inflammation: A Meta-Analysis. “The analysis of nine studies revealed significant weight reduction and BMI decreases with L. plantarum supplementation compared to a placebo”
• The Effect of the Lacticaseibacillus paracasei BEPC22 and Lactiplantibacillus plantarum BELP53 Combination (BN-202M) on Body Fat Percentage Loss in Overweight Individuals: A Randomized, Double-Blind, Placebo-Controlled Study. “Akkermansia showed a statistically significant with these probiotics”
• Lactobacillus paracaseiN1115 attenuates obesity in high-fat diet-induced obese mice.

Diabetes

While many studies show promise, the evidence is still mixed, and more long-term research is needed to determine the most effective probiotic strains and protocols for diabetes management [Probiotics Contribute to Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis] – study was pre-Akkermansia availability.

• A Critical Perspective on the Supplementation of Akkermansia muciniphila: Benefits and Harms.
  “Accumulating evidence indicated Akkermansia as a promising therapeutic probiotic against metabolic disorders such as obesity, type 2 diabetes and cardiovascular diseases.”

• Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes.
• Review of Literature on Akkermansia muciniphila and its Possible Role in the Etiopathogenesis and Therapy of Type 2 Diabetes Mellitus.
• Molecular Mechanism of Pasteurized Akkermansia muciniphila in Alleviating Type 2 Diabetes Symptoms.
• Live and pasteurized Akkermansia muciniphila ameliorates diabetic cognitive impairment by modulating gut microbiota and metabolites in db/db mice.
• Akkermansia muciniphila: a potential candidate for ameliorating metabolic diseases.
• Function of Akkermansia muciniphila in type 2 diabetes and related diseases.
• Health and Disease: Akkermansia muciniphila, the Shining Star of the Gut Flora.
• [Research Progress on the Role of Akkermansia Muciniphila in Prevention and Treatment of Diabetes Mellitus].

And

• Ameliorative Effects of Lactobacillus paracasei L14 on Oxidative Stress and Gut Microbiota in Type 2 Diabetes Mellitus Rats.
• Anti-Diabetic Effect of Lactobacillus Paracasei Isolated from Malaysian Water Kefir Grains.
• Screening of Potential Probiotic Lactobacillaceae and Their Improvement of Type 2 Diabetes Mellitus by Promoting PI3K/AKT Signaling Pathway in db/db Mice.
  •  Lactiplantibacillus plantarum
  • Limosilactobacillus fermentum
• Heat-Killed Lactiplantibacillus plantarum LRCC5314 Mitigates the Effects of Stress-Related Type 2 Diabetes in Mice via Gut Microbiome Modulation.
• Effects of Lactobacillus plantarum supplementation on glucose and lipid metabolism in type 2 diabetes mellitus and prediabetes: A systematic review and meta-analysis of randomized controlled trials.
• Effect of postbiotic Lactiplantibacillus plantarum LRCC5314 supplemented in powdered milk on type 2 diabetes in mice.
• Lactobacillus paracaseiN1115 attenuates obesity in high-fat diet-induced obese mice.
• A Potential Synbiotic Strategy for the Prevention of Type 2 Diabetes: Lactobacillus paracasei JY062 and Exopolysaccharide Isolated from Lactobacillus plantarum JY039.

Bottom Line

My (incomplete) review of the many many studies suggests that four species of probiotics are the most likely to help with Obesity and Diabetes. Below are links to manufacturers that directly sell my preferred single strain probiotics. This means that you will get the probiotics within weeks (or days) of being manufactured (i.e. Very fresh and live probiotics).

• Akkermansia muciniphila
• Lactiplantibacillus plantarum aka Lactobacilllus plantarum
• Limosilactobacillus fermentum aka Lactobacilllus fermentum
• Lactobacillus Paracasei

Suggested daily dosage is a therapeutic 50 BCFU/day for the Lactobacillus, and likely a capsule of Akkermansia muciniphila (Pendulum is the established provider).

For the Lactobacillus, I find using powder dissolved in a glass of warm water works very well. It often has a side effect of inhibiting wanting to have a treat and gives a satisfied feeling in the gut. Taking them as capsules do not seem to have that effect.

We are likely the sole firm claiming the use of AI for microbiome analysis that is in conformity today. Most firms in this area that claim using AI, refuse to even disclose which type of AI that they are using. Since our founding, we have been OPEN DATA. The logic used for every suggestion is show and links to every data source. We are about to file patents for our proprietary, PATENT PENDING, algorithms – meaning that shortly even the algorithms will be available for inspection.

Our core AI model is an old classic: fuzzy logic expert systems.

The foundations of fuzzy logic were laid in 1965 by Lotfi Zadeh, a professor at the University of California, Berkeley. In his seminal paper “Fuzzy Sets”, Zadeh introduced the concept of fuzzy set theory, which allows for degrees of truth rather than the classical binary true or false [A brief History of Fuzzy Logic].

The concept of expert systems, which are computer programs designed to emulate the decision-making abilities of a human expert, began to take shape in the 1960s. One of the earliest and most notable examples was MYCIN, developed in the early 1970s at Stanford University. MYCIN was designed to diagnose bacterial infections and recommend antibiotics based on a set of if-then rules derived from expert knowledge. [Knowledge Discovery from Medical Data and Development of an Expert System in Immunology]

I have had a few emails asking if I am over-flagging these issues on MicrobiomePrescription.

I used Perplexity.AI to get some numbers…. here is what was reported (with references to sources). Given the typical reasons that people get microbiome samples, the rates appear reasonable.

1. The National Institute of Health (NIH) statistics indicate that biofilm formation is present in about 65% of all bacterial infections and approximately 80% of all chronic infections.
2. In the context of human health, biofilms are responsible for about 80% of bacterial infections

https://www.perplexity.ai/search/what-percentage-of-microbiome-fLRJ2SghTLCSWDdlo2AGKw#0

1. D-lactic acidosis is considered rare in humans overall, but it may be underdiagnosed. Some experts suggest it should be looked for more often in cases of unexplained metabolic acidosis.
2. It is most commonly associated with short bowel syndrome (SBS). The incidence of SBS is estimated at approximately 2 persons per million per year. While not all SBS patients develop D-lactic acidosis, they are at higher risk.
3. In patients with short bowel syndrome, D-lactic acidosis appears to be a relatively frequent complication. One study found that all 29 SBS patients examined had experienced neurologic symptoms associated with D-lactic acidosis at some point
   [NOTE: SBS have a very high incidence of SIBO [src], so SIBO likely have an increased risk of d-lactic].

https://www.perplexity.ai/search/what-percentage-of-microbiome-fLRJ2SghTLCSWDdlo2AGKw#1

• Histamine intolerance is estimated to affect approximately 1-3% of the general population. However, some experts suggest this number could be higher as the condition is often underdiagnosed.
• Among people with digestive symptoms or conditions like IBS, IBD, and Crohn’s disease, a surprisingly high 30-55% may have histamine intolerance.
• One study found that diamine oxidase (DAO) deficiency, which is associated with histamine intolerance, was present in up to 44% of the control population.
• A more dramatic estimate suggests that histamine intolerance may affect 50-60% of the population, according to one source. However, this figure seems significantly higher than other estimates and may need further verification.
• In people with digestive symptoms, one study showed that 30-55% also have histamine intolerance.
• https://www.perplexity.ai/search/what-percentage-of-microbiome-fLRJ2SghTLCSWDdlo2AGKw#2

A reader asked, Which genus should I give highest priority in general?

This is an easy answer using the Conditions populated from studies on the US National Library of Medicine on 127 different conditions. The results are below for those that are seen in at least 10% of conditions.

Below that is a table showing the direction of shifts.

Taxa Name	Percentage Of Conditions with Shifts
Bifidobacterium	55
Prevotella	54
Bacteroides	52
Faecalibacterium	51
Lactobacillus	47
Blautia	44
Ruminococcus	43
Streptococcus	41
Roseburia	40
Escherichia	40
Clostridium	38
Parabacteroides	37
Coprococcus	34
Alistipes	33
Eubacterium	31
Shigella	31
Veillonella	30
Akkermansia	29
Fusobacterium	27
Dorea	27
Enterococcus	27
Anaerostipes	26
Dialister	25
Collinsella	25
Haemophilus	25
Klebsiella	25
Odoribacter	25
Megamonas	23
Bilophila	22
Desulfovibrio	22
Subdoligranulum	22
Lachnospira	21
Turicibacter	21
Phascolarctobacterium	20
Eggerthella	20
Enterobacter	20
Butyricicoccus	18
Oscillibacter	18
Porphyromonas	18
Megasphaera	17
Lachnoclostridium	16
Sutterella	16
Staphylococcus	16
Butyricimonas	16
Actinomyces	16
Oscillospira	15
Romboutsia	14
Parasutterella	14
Barnesiella	14
Campylobacter	14
Anaerotruncus	14
Paraprevotella	14
Methanobrevibacter	14
Catenibacterium	13
Butyrivibrio	13
Flavonifractor	13
Citrobacter	13
Coprobacillus	12
Adlercreutzia	12
Parvimonas	12
Rothia	12
Pseudomonas	12
Acidaminococcus	11
Fusicatenibacter	11
Gemella	11
Corynebacterium	11
Agathobacter	11
Ruminiclostridium	11
Lactococcus	11
Weissella	11
Slackia	10
Alloprevotella	10
Eisenbergiella	10

Direction Of Shifts for each bacteria

For some it is balanced, for others only one direction is significant.

• “H” means that this genus for medical conditions are abnormally high for people with a condition
• “L” means that this genus for medical conditions are abnormally low for people with a condition
• NOTE: For some conditions, both High and Low are reported, i.e. the population of this genus becomes abnormal. For details see: https://microbiomeprescription.com/Library/PubMed
  

Taxa Name	Direction of shift	Percentage
Actinomyces	H	13
Agathobacter	L	8
Akkermansia	H	21
Akkermansia	L	15
Alistipes	H	20
Alistipes	L	21
Anaerostipes	H	11
Anaerostipes	L	17
Anaerotruncus	H	11
Bacteroides	H	37
Bacteroides	L	37
Barnesiella	L	9
Bifidobacterium	H	32
Bifidobacterium	L	43
Bilophila	H	14
Bilophila	L	9
Blautia	H	28
Blautia	L	27
Butyricicoccus	L	16
Butyricimonas	H	8
Butyricimonas	L	10
Butyrivibrio	L	11
Campylobacter	H	13
Catenibacterium	H	8
Citrobacter	H	10
Clostridium	H	25
Clostridium	L	20
Collinsella	H	18
Collinsella	L	12
Coprobacillus	H	10
Coprococcus	H	15
Coprococcus	L	28
Corynebacterium	H	8
Desulfovibrio	H	18
Dialister	H	11
Dialister	L	18
Dorea	H	18
Dorea	L	15
Eggerthella	H	17
Enterobacter	H	14
Enterococcus	H	21
Enterococcus	L	13
Escherichia	H	37
Eubacterium	H	12
Eubacterium	L	26
Faecalibacterium	H	18
Faecalibacterium	L	44
Flavonifractor	H	12
Fusobacterium	H	22
Gordonibacter	H	8
Haemophilus	H	13
Haemophilus	L	15
Klebsiella	H	23
Lachnoclostridium	H	12
Lachnospira	L	14
Lactobacillus	H	28
Lactobacillus	L	31
Megamonas	H	14
Megamonas	L	14
Megasphaera	H	13
Methanobrevibacter	H	13
Neisseria	H	8
Odoribacter	H	17
Odoribacter	L	12
Oscillibacter	H	14
Oscillospira	H	11
Parabacteroides	H	29
Parabacteroides	L	16
Paraprevotella	H	8
Paraprevotella	L	8
Parasutterella	L	11
Parvimonas	H	8
Phascolarctobacterium	H	13
Phascolarctobacterium	L	13
Porphyromonas	H	14
Prevotella	H	40
Prevotella	L	36
Pseudomonas	H	9
Romboutsia	L	11
Roseburia	H	13
Roseburia	L	34
Rothia	H	11
Ruminococcus	H	27
Ruminococcus	L	25
Shigella	H	30
Staphylococcus	H	14
Streptococcus	H	36
Streptococcus	L	14
Subdoligranulum	H	11
Subdoligranulum	L	15
Sutterella	H	11
Sutterella	L	8
Turicibacter	H	11
Turicibacter	L	14
Veillonella	H	21
Veillonella	L	12

Where are the buttons to generate these?

• Just Give Me Suggestions

• Cross Validated Suggestions

Key Differences

Description	Just Give Me	Cross Validated
Bacteria Considered	All bacteria	Only bacteria associated with condition from Pub Med Studies
Suggestions	All Modifiers	Only modifiers reported to help at least one of the conditions from Pub Med Studies
Priority	Weight given	No ranking, all are both agree without ranking
Target Audience	Microbiome educated Medical types	Conservative Medical Type that are not familiar with the microbiome and recent research.
Condition Citations	No condition citations included	Most available condition citations for bacteria shift and suggestions are listed on one page with hyperlinks.
Microbiome Citations	All are available by individual links.	Only a token number of citations on how suggestions modify bacteria (why? full list can be massive)
Algorithm	Monte Carlo Model with multiple algorithms	Single Algorithm using above 85%ile and below 15%ile as bacteria selection criteria
Goal	Best suggestions based on the art of the microbiome	Educating and getting buy-in with conventional MDs
Special Goals	Focus on the holistic microbiome independent of specific diagnosis	Help MD pick the best for the microbiome choice from possible pro-forma treatments.

A possible example: the MD wants to prescribe an antibiotics for a condition. Usually, there are a half dozen possible choices. Ideally, the MD will be willing to go with the one that is best for the microbiome when shown the evidence from the computations.

Which is best?

The Cross-Validated has a limited list because it is very time consuming to populate the data needed for it. For items like biofilm, d-lactic acid and histamine — it is likely the best choice but the suggestions should be checked with the “Just give me suggestions” and the final suggestions should be only ones that both agree with — subject to review by your medical professional.

A person asked:

Should I be taking flushing niacin with Crohn’s Disease. I feel better after taking it, but I read that it encourages the release of prostaglandins, particularly prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2), rather than histamine.

My first step is to go to Perplexity.AI and ask questions there and then check the sources cited. I then use this to jump into PubMed to get better information. As with all AI, you need to learn to ask clear specific questions.

Questions:

1. What are the consequences of using flushing niacin with Crohn’s Disease?
   • The full answer.

• After reading the studies, I go to the PubMed Summary and look at Similar articles and Cited By. Often this will lead to other studies.

• Next I return to Perplexity and look at the follow up questions that it proposes.

• The process is repeated — every item to be consider should check the source study.

The next step is take all of the key words above and do a full text search on PMC

• Crohn’s Disease
• Niacin
• prostaglandin D2 (PGD2)
• D prostanoid receptor 1 (DP1)
• inflammation. 

For words that you are not familiar with, just ask Perplexity.

• “What is the role of D prostanoid receptor 1 (DP1).”
  • Full Answer.
  • Follow up Question (asking the question from a different direction) “What is its impact on Crohn’s disease”

Searching PMC

Just go to the site: https://www.ncbi.nlm.nih.gov/pmc/

• Entering: Niacin and inflammation => 12,000 hits
  • Changing to: Niacin inflammation Crohn’s => 1127 hits

I changed to default order (most relevant first) and spotted some interesting titles:

• Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications [2019]
• Niacin ameliorates ulcerative colitis via prostaglandin D₂‐mediated D prostanoid receptor 1 activation [2017]
• Effects of ileocolonic delivered vitamin B₂, B₃[NIACIN] and C (ColoVit) or the Groningen anti-inflammatory diet on disease course and microbiome of patients with Crohn’s disease (VITA-GrAID study): a protocol for a randomised and partially blinded trial [2023] – Pending study
• Niacin Ameliorates Neuro-Inflammation in Parkinson’s Disease via GPR109A
  • Low-Dose Niacin Supplementation Improves Motor Function in US Veterans with Parkinson’s Disease: A Single-Center, Randomized, Placebo-Controlled Trial [2021]
• Niacin Suppresses Progression of Atherosclerosis by Inhibiting Vascular Inflammation and Apoptosis of Vascular Smooth Muscle Cells [2015]
• Nutrient Intake of Crohn’s Patients: Is There Consistency between Crohn’s Disease Activity Index, Subjective Global Assessment and Body Mass Index? [2021]
  • Daily energy, carbohydrate, monosaccharide, starch, sucrose, fructose, poly-unsaturated fatty acids, omega-3 fatty acids, fiber, vitamin E and C, thiamine, niacin, pyridoxine, Mg, P, Fe, Cu, Zn intakes were significantly lower in Crohn’s Group than in Control Group.
  • Nutritional deficiencies in patients with Crohn’s disease in remission [2006]
    • “More than 50% of patients had low plasma concentrations of vitamin C (84%), copper (84%), niacin (77%), and zinc (65%).”
• Association between dietary niacin intake and cognitive function in the elderly: Evidence from NHANES 2011–2014 [2023]
  • “High niacin intake favors a decrease in the incidence of low cognition”

This study was of particular interest: Identifying metabolic shifts in Crohn’s disease using ‘omics-driven contextualized computational metabolic network models [2023]

“Interestingly, high-dose vitamin B3 treatment has been shown to ameliorate ulcerative colitis through increased prostaglandin D2 synthesis in mice⁵⁴. Thus, niacin supplementation can be a potential therapeutic target to be investigated in CD as well. In addition, untargeted metabolomics showed the dysregulation of pathways related to pyrimidine, glutamate, and nitrogen metabolism. “

Second Question: Niacin and MCAS

Mast cell activation syndrome (MCAS) is another issue that the person is dealing with.

Asking more we get a yes/no with lacking studies.

Digging more we see other things that are EITHER/OR. Thus PGD2 in isolation is not connected to activation; rather activation is conditional on multiple factors (one of them is PGD2). “MCAS is associated with a variety of mediators beyond PGD2, including histamine, tryptase, leukotrienes, cytokines, heparin, PAF, neuropeptides, and other eicosanoids.”

• “Tests for serum PGD₂ have similar drawbacks, as processing of peripheral blood samples can trigger non-MC cellular elements to release PGD₂; ingestion of niacin is also associated with elevations in serum PGD₂ ” [1994] so this may rendering test results invalid.
• Using the Right Criteria for MCAS [2023]
  • “Mediators other than tryptase, including urinary metabolites of histamine, prostaglandin D2 (PGD2), and leukotrienes, are also available but less specific for MCs and MCAS [28, 29, 30••]. Additionally, the sensitivity and specificity of these markers have not been determined, nor have the reliable indicators of systemic MC activation, such as significant increase and cut-off levels. ‘
  • “PGD2, while primarily released by MC, is also produced by other immune and nonimmune cell types [42–45]..elevations in PGD2 might be due to a pathologic process independent of MC activation.”
• Concentrating on Niacin and Histamine, Perplexity gives plus and minus, concluding “In summary, niacin can both positively and negatively impact histamine levels and symptoms.” So, our bottom line is that it depends on the individual.

The responses mention S-adenosylmethionine (SAMe) being consumed with Niacin.

Which implies SAMe should be taken with the Niacin.

Bottom Line

The final decision is always the person in consultation with their medical professional. Using Niacin as a treatment for Crohn’s Disease is heading for clinical trial and suggested by a 2023 metabolic shifts study on Crohn’s. Given the low risk (assuming medical monitoring for niacin risk), I personally would favor doing it (making sure their usual MD is aware of the dosage and a possible need to monitor).

The purpose of this post is to show a method of gathering information to make better health choices. I have fallen in love with Perplexity.AI because it cites studies on PubMed often and it’s suggestions are easy to verify and evaluate. It also prompts for follow up questions.

We discovered a multitude of deficiencies that may need to be supplemented (factoring in poor absorption due to Crohn’s) including:

• SAMe (because of the niacin use)
• fructose,
• poly-unsaturated fatty acids,
• omega-3 fatty acids,
• vitamin E and C,
• thiamine,
• niacin,
• pyridoxine,
• Mg,
• P,
• Iron,
• Copper,
• Zinc
  

This lead to the logic questions: What are all the deficiencies seen in Crohn’s disease that can be supplemented? Full Answer.

P.S. The time it took to do the above was about 90 minutes,

Over the years, I ended up with some simple rules for what I will buy. The rules are simple:

• Trademarked/copyrighted/patented species, ideally ones with some research. All of them are listed on this page with links to the research. Ideally, just the one researched for your conditon.
• Single species with (almost) no fillers. There are precisely three sources that I use:
  • Custom Probiotics :they list all of their strains — many are researched on the above list. No other ingredients just the bacteria.
  • Maple Life Science™: No strains yet, but shipments usually have manufactured date within 4 weeks of arrival (i.e. FRESH). Contains FOS
  • Bulk Probiotics: US based Newbie — but has some species not available at the other two sites. No other ingredients just the bacteria. Specifically, Lactobacillus Jensenii that has great potential for Crohn’s disease.
• NOTE: none of these sell though retail outlets. This keeps their costs down and their product fresh.

Personal Experience

This family experience with all of the single strain probiotics has been:

• If we have not used before, we notice changes within 1-3 days in stools, symptoms, etc. These may not always be desired symptoms (i.e. one probiotic before bed, kept us awake all night; other probiotics give us deeper and longer sleep than normal). In some cases, changes are observed within 60 minutes. Changes of stools are a common change.
• We usually do one new probiotic at a time for 2 weeks to get “a feel” for what it does
• We constantly rotate – never more than 1 month on any probiotic “It has done what it is going to do“

“If there is no changes, the probiotic is dead, Jim” or not of benefit to you. Move on. A common observation that we saw using most probiotics purchased from local stores.

Medical Claims

I do not trust any claims on the bottle

The outcome of the first series of health claim applications for probiotics in Europe as evaluated by the European Food Safety Authority (EFSA) has, up to 2013 almost completely yielded negative results. All recent applications also have been rejected, including the latest on prevention of mastitis in breastfeeding mothers. 

The ascent of the blessed: regulatory issues on health effects and health claims for probiotics in Europe and the rest of the world [2018]

I don’t trust retail mixtures with good reasons:

• Assessment of commercial probiotic bacterial contents and label accuracy [2011]
  • Misspelled organisms: 32% — using outdated names higher!
    • I.e. it is Limosilactobacillus reuteri and not Lactobacillus Reuteri
    • it is Lacticaseibacillus casei and not Lactobacillus casei
  • Just 27% of claims of viable organisms met or exceeded their label claim
• Evaluation of deficiencies in labeling of commercial probiotics [2003]
  • Misspelled organisms: 25%
  • Bacterial species were misidentified 35-43% of the time
  • Misidentifications included stating a name that had been changed
    • i.e. “Streptococcus faecium” and not Enterococcus faecium
    • Non existent species: “Lactospore sporogenes“
• Identification and antibiotic resistance of isolates from probiotic products. Abstracts of 101st ASM General Meeting. The American Society for Microbiology, Washington DC, USA,
  • for 30 dried probiotic supplements tested,
  • 11 contained no viable bacteria,
  • only 7 contained all claimed species
  • 18 had species other than those on-label.
• Deficiencies in microbiological quality and labelling of probiotic supplements [2002]
  • 63% of the UK products tested were below standard.
  • Enterococcus faecium (not stated on label) and was labelled with the misleadingand invalid name ‘‘L. bifidus’’.
• Microbiological Quality and Antimicrobial Resistance of Commercial Probiotic Products for Food-Producing Animals [2024]
  • 64.4% were incorrectly labeled in either number of viable cells or bacterial species
  • 51.6% exhibited resistance to at least one antimicrobial agent
  • 26.8% had a lower number of viable cells than their label claims, No viable Lactobacillus was found in some products 
  • 57.8% comprised other species rather than those claimed on the contents
• More Information Needed on Probiotic Supplement Product Labels [2019]
  • This cites this as the minimum recommended standard.
    • Genus and species names, which should adhere to current scientifically valid nomenclature.
    • Strain designations for each strain in the product. Designations used should enable tracking of the strain to entries in strain depositories and linking to published studies.
    • Statement of quantity (using CFU or other validated measure) of live/active microorganisms through the use-by date.
    • Use-by date.
    • Statement of benefit is not required, but if present must be supported by a human study showing the benefit at the dose delivered in the product.
    • Proper storage conditions Required.
    • Company contact information.
  • Warns of genetic drift (bacteria mutations) and cites the popular
    • L. rhamnosus (GG) that exhibited multiple genotypes in consumer products (Sybesma et al., 2013). So the bottom of LGG you buy may not be the same strain as the studies used.
• Improving End-User Trust in the Quality of Commercial Probiotic Products [2019] shows the evidence issue, manufacturer will toss the kitchen sink into a blend and make questionable claims to promote sales.

I have the following information on Custom Probiotics strains on my CFS Remission Site and reposting here so people can find them faster.

• B. Lactis, Strain BL-04
• B. Bifidum, Strain Bb-06
• B. Breve Probiotic Powder, Strain BB-18
• B. Infantis, Strain Bi-26
• B. Longum, Strain BL-05
• L. Acidophilus, Strain LA-14
• L. Brevis, Strain LBR-35
• L. Bulgaricus Probiotic Powder, Strain LB-87
• L. Casei Probiotic Powder, Strain LC-11
• L. Fermentum Probiotic Powder, Strain SBS-1
• L. Gasseri Probiotic Powder, Strain LG-36
• L. Paracasei Probiotic Powder, Strain LPC-37
• L. Plantarum, Strain LP-115
• L. Reuteri Probiotic Powder, Strain UALre-16
• L. Rhamnosus Powder, Strain LR-32
• L. Rhamnosus Probiotic Powder, Strain GG
• L. Salivarius, Strain LS-33
• S. Thermophilus Probiotic Powder, Strain ST-21

Some of these have studies, see the researched list.

Today, I looked at the bacteria associated to histamine conditions and found the quality of research lacking. I had imported a lot of data from Alison Vickery web site. Unfortunately some of the bacteria cited as producing histamines according to Kyoto Encyclopedia of Genes and Genomics lack the enzymes to produce histamine. Today, I spent the morning checking published studies on the US National Library of Medicine to see if there is any evidence of histamine production there — little luck. As a result, I deleted the data since it was not at the desired quality.

Quick Summary

• It is strongly recommended that the sources be read before taking any actions
• Items that may help:
  • DAO
  • Anti-Histamines
  • HNMT histamine N-methyltransferase (prescription)- is possible help
• Items to Avoid:
  • Vitamin B1
  • Vitamin C
  • Histamine Liberators [2015] – Many of these items have zero histamine (research is sparse)
    • Tomatoes, eggplant, spinach, fish, chicken and every stored meat. All fermented food (cheeses, sausages, sauerkraut, wine, beer, champagne …
    • Pineapple, bananas, citrus fruits, strawberries, nuts, papaya, tomatoes, liquorice, spices, legumes, cocoa [2021] [2005], alcohol; fish, seafood, pork, egg white
    • MECHANISM: “The presence of putrescine, which may interfere with histamine degradation by the DAO enzyme at the intestinal level, could partly explain the reason why certain foods (i.e., citrus fruits and bananas) were also frequently reported in low-histamine diets” [2021] This link has a table showing the amount in various foods.
    • In Medicine:
      • Painkillers (morphine, pethidine, codeine, metamizole, antiflogistics (acetylsalicylic acid), antibiotics (d-cycloserine, chloroquin, pentamidine), anti-hypotensives (dobutamine), antihypertensive drugs (verapamil, alprenolol), antitussives (codeine), cytostatics (cyclophosphamide), diuretics (amilorid), iodine-containing contrast medium, local anaesthetics (mesocaine, procaine, marcaine, prilocaine), muscle relaxant (d-tubocurarin), narcotics – anaesthetics (barbiturates, thiopental) Painkillers – antipyretics (acetylsalicylic acid, diclofenac, flurbiprofen, indomethacin, ketoprofen, mefenamin, naproxen…) 
  • DAO Reducers:
    • Antiarrhythmics (verapamil, propafenone), antibiotics (cefuroxime, cefotiame, acidum clavulanicum, doxycyclinum, isoniazid, framycetin), painkillers (metamizole), antidepressants, psychiatric medication (amitriptiline, diazepam, inhibitors MAO–1, haloperidol), antiemetics (metoclopramide), antihistamines (promethazine, cimetidine), antihypertensive drugs (dihydralazine), antimalarials (chloroquin), bronchodilators (aminophylline, theophylline), diuretics (furosemide), mucolytics (N-acetylcysteine, ambroxol), muscle relaxant (alcuronium, pancuronium, d-tubocurarin), antiseptics (acriflavinium chloride), chinidin 
  • Aspirin (Acetylsalicylic acid)
  • NAC (N-Acetylcysteine) aka Acetylcysteine
  • L-Glutamine [2022]
  • Nonsteroidal anti-inflammatory drugs
    • ibuprofen.
    • naproxen.
    • diclofenac.
    • celecoxib.
    • mefenamic acid.
    • etoricoxib.
    • indomethacin.

See below for detail

From Low-Histamine Diets: Is the Exclusion of Foods Justified by Their Histamine Content? [2021]

The PDF below is from the Swiss Interest Group Histamine Intolerance (SIGHI) food list that appears to be awesome! They also have a smart phone application.

Analysis and Research

This post is the next step — checking the latest literature and summarizing it in this post. I jump started by using Perplexity.

• Genetic Factors
  • “An increased risk for migraines was demonstrated in patients with some DAO genotypes and allelic variants” [2015]
    • “A high incidence of DAO deficiency at nearly 90% was observed in migraine patients [2018]
    • “a study demonstrated that oral ingestion of capsules with DAO significantly reduces headaches in migraine patients” [2018]
  • Genetic mutations that result in lower production or impaired function of the DAO enzyme, which breaks down histamine.
    • SNP: Amine Oxidase Copper Containing 1 (AOC1) [2023]
    • rs2052129 (minor allele T)  [2011][2024]
    • rs2268999 (minor allele T) [2011][2024]
    • rs10156191 (minor allele T) [2011][2024] 
    • rs1049742 (minor allele T) [2011][2024]
    • rs1049793 (minor allele G) [2011][2024] 
    • rs1050891 (C314T polymorphism) with the minor T allele [2010]
    • Gastrointestinal Disorders
• Medications: Certain medications like antibiotics, antidepressants, antiarrhythmics, muscle relaxants, and NSAIDs can inhibit DAO activity or block histamine breakdown. Table below is from a [2021] article.

Medications	Generic Name
Analgesics	Acetylsalicylic acid, Metamizole, Morphines, Nonsteroidal anti-inflammatory drugs, Pethidine
Antiarrhythmics	Propafenon
Antibiotics	Cefuroxime, Cefotiam, Isoniazid, Pentamidine, Clavulanic acid, Chloroquine
Antidepressants	Amitriptylline
Antifungal	Pentamidine
Antihypertensives	Verapamil, Alprenolol, Dihydralazine
Antihypotensives	Dobutamine
Antimalarial	Chloroquine
Broncholytics	Aminophylline
Cytostatics	Cyclophosphamide
Diuretics	Amiloride
H2 receptor antagonists	Cimetidine
Local anesthetics	Prilocaine
Motility agents	Metoclopramide
Mucolytics	Acetylcysteine, Ambroxol
Muscle relaxants	Pancuronium, Alcuronium, D-Tubocurarin
Narcotics	Thiopental
Vitamins	Ascorbic acid (Vitamin C), Thiamine (Vitamin B1)

• Diet: Consuming foods rich in histamine (aged cheese, fermented foods, alcohol, etc.) can overwhelm the body’s ability to break down histamine, leading to an accumulation.
  • Repeatedly state with reference in this [2021] study.
  • Low-Histamine Diets: Is the Exclusion of Foods Justified by Their Histamine Content? [2021]
  • “The dietary treatment of histamine intolerance reduces the abundance of some histamine-secreting bacteria of the gut microbiota in histamine intolerant women. A pilot study” [2022]
    • “Reduction of Proteus and Raoultella and the species Proteus mirabilis. “
• Perplexity AI suggested: “Conditions like inflammatory bowel disease (IBD), leaky gut syndrome, and other gastrointestinal disorders can impair DAO production and histamine breakdown.” Unfortunately it’s sources were poor. Checking PubMed, we see the following studies indicate that it appears to apply possibly apply only to one type of IBS.
  • “DAO levels were significantly higher in Crohn’s patients with the active stage compared to controls.” [2019]
  • “histamine levels were normal in CD and UC.” [2015]
  • “subjects with irritable bowel syndrome[IBS] could be discriminated from healthy controls using their metabolic fingerprints… Levels of some urinary metabolites including histamine correlated significantly with irritable bowel syndrome symptom severity scores.” [2019]
  • “The mast cells’ histamine release appears linked to GI-involving diseases like celiac disease (CD), eosinophilic gastroenteritis (EGE), and mast cell activation syndrome (MCAS) “[2020]

The above chart from Noninvasive biomarkers of gut barrier function identify two subtypes of patients suffering from diarrhoea predominant-IBS: a case-control study [2018] shows there is not a reduction of DAO with IBS, and an increase with Crohn’s Disease (as cited in another study above). When IBS was decomposed by type, one was below the controls and the other was above the controls (same level as CD).

• Intestinal barrier dysfunction: Impaired intestinal barrier function (leaky gut) can allow increased absorption of histamine from the gut into the bloodstream, contributing to histamine overload.
  • No clear strong evidence found, a reasonable speculation
  • But evidence of bacteria shifts:
    • Reduced Bifidobacteriaceae (Bifidobacterium), Butyricimonas, and Hespellia (P = 0.025); Roseburia increased [2018]
    • Reduced Prevotellaceae, Ruminococcus, Faecalibacterium and Faecablibacterium prausnitzii [2022],
• Bacterial overgrowth: An overgrowth of certain bacteria in the gut can lead to excessive production of histamine, overwhelming the DAO enzyme’s capacity to break it down
  • “a significantly higher abundance of histamine-secreting bacteria, including the genera Staphylococcus and Proteus, several unidentified genera belonging to the family Enterobacteriaceae and the species Clostridium perfringens and Enterococcus faecalis” [2022]

Probiotics

For a list of studies, click here. The following has some evidence of reducing histamines

• Bifidobacterium bifidum
• Bifidobacterium lactis
• Enterococcus faecium
• Lactobacillus casei Shirota
• Lactobacillus paracasei 
• Lactobacillus reuteri
• Lactobacillus rhamnosus GG & GR-1
• Mutaflor (Escherichia coli strain Nissle 1917)

Caution should be taken because one strain may produce histamine and another reduces it. The chart below show different strain of Lactobacillus reuteri. Some produces histamine and others do not. Bifidobacterium are in general safe. Lactobacillus has risks — if you try them, do one at a time when you are stable. Remember most probiotics are sold by Species and not Strain; same species from two different manufacturers may be different strains — so how lucky do you feel.

From prediction to function using evolutionary genomics: human-specific ecotypes of Lactobacillusreuteri have diverse probiotic functions[2014].

Your level of Histamine Producers in your Gut

This is now on Microbiome Prescription and is based on the count of species known to produce histamine in your sample.

Histamine N-methyltransferase 

A reader asked about this item that I missed.

Histamine N-methyltransferase (HNMT) is an enzyme that plays a crucial role in the inactivation of histamine in central nervous system, kidneys and bronchi. Inhibition of HNMT is known to have a potential role in treating attention-deficit hyperactivity disorder, memory impairment, mental illness and neurodegenerative illnesses.

Molecular docking studies of Nigella sativa L and Curcuma xanthorrhiza Roxb secondary metabolites against histamine N-methyltransferase with their ADMET prediction [2021]

Genetic polymorphisms in histamine-related genes, including FcεRI and HNMT, were suggested to be involved in mast cell activation and histamine metabolism. Several genetic polymorphisms of leukotriene-related genes, such as ALOX5, LTC4S, and the PGE2 receptor gene PTGER4, were suggested to be involved in leukotriene overproduction, a pathogenic mechanism. 

Molecular genetic mechanisms of chronic urticaria [2013]

From Drug Repurposing to Inhibit Histamine N-Methyl Transferase[2023] we have this chart suggesting that Metoprine is the best performing of the drugs tested.

There is a sparseness of explicit studies, but it may be worth discussing with your MD who is better able to evaluate the literature.