A reader wrote today me today on my Histamine post from July 2018

“Hi Ken, thank you for all the info you provide with this blog. In an older post, you recommended Lactobacillus Rhamnosus GG and E. Coli Nissle 1917 for reducing histamine. Does this advice still hold true? Are there any other strain worth trying? “

I will revisit the two probiotics he asked about (since more data is always coming in). See the link post for more information on Histamine in general.

Lactobacillus Rhamnosus

one billion viable microencapsulated bacteria Lactobacillus rhamnosus GG in combination with fructooligosaccharides to complex therapy of premature children results in regulation of cytokine balance with the tendency to reduction of an inflammatory process and has a preventive effect concerning allergopathy formation.

INVESTIGATION OF PROTECTIVE EFFECTS OF SYNBIOTICS ON ALLERGOPATHY FORMATION. 2018

Treatment with the probiotic mixture(four species of probiotics, Bifidobacterium lactis, Lactobacillus casei, Lactobacillus rhamnosus, and Lactobacillus plantarum) and sodium butyrate reduced ear thicknesses, the quantity of leaked Evans blue, and serum histamine values, while increasing serum IL-10 values.

Anti-Inflammatory Effects of a Mixture of Lactic Acid Bacteria and Sodium Butyrate in Atopic Dermatitis Murine Model. 2018

• “The (Lactobacillus rhamnosus ) strains are neither haemolytic nor producer of biogenic amines such as histamine, putrescine, cadaverine and tyramine.  ” [2014]
• Systemic effects of ingested Lactobacillus rhamnosus: inhibition of mast cell membrane potassium (IKCa) current and degranulation. [2012]
• Probiotic Lactobacillus rhamnosus downregulates FCER1 and HRH4 expression in human mast cells.[2011]
• Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as budesonide at reducing inflammation in a murine model for chronic asthma. [2014]

Escherichia Coli Nissle 1917 (Mutaflor)

We do not have such clarity for Mutaflor. We do find that it reduces allergies:

• Tolerability and clinical outcome of coseasonal treatment with Escherichia coli strain Nissle 1917in grass pollen-allergic subjects [2014]. NOT BETTER THAN PLACEBO
• Oral administration of Escherichia coli Nissle 1917 prevents allergen-induced dermatitis in mice.[2011]
• Probiotic Escherichia coli Nissle 1917 suppresses allergen-induced Th2 responses in the airways. 2009

Other Strains

” Histamine derived from lactobacilli isolates is considered to be a potential immunomodulator able to interact with the host immune system….
 However, our findings indicated that the impact of lactobacilli histamine is strictly strain-dependent and concentration dependent.    ” [2018]

“These probiotic strains showed neither hemolytic activity nor mucin degradation activity, and they did not produce ammonia or biogenic amines (i.e., cadaverine, histamine or tyramine)

Safety Evaluations of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI. 2018

“Here, we investigated the effect of Lac-B, a mixture of freeze-dried Bifidobacterium infantis and Bifidobacterium longum, on the allergy-related histamine signaling. … Our findings indicate that oral administration of Lac-B showed significant anti-allergic effect through suppression of both H1R and HDC gene expression followed by decrease in H1R, HDC protein level, and histamine content. 

Suppression of histamine signaling by probiotic Lac-B: a possible mechanism of its anti-allergic effect. 2008

• “Use of a probiotic mixture containing Bifidobacterium animalis subsp. lactis BB12 and Enterococcus faecium L3 in atopic children….
  significantly reduced the use of oral antihistamines, ” [2018]

Products Claiming…

There are some probiotic mixtures claiming not to produce histamines, for example: “ProBiota HistaminX contains only probiotic species that are considered “histamine-friendly” and excludes those known to produce histamine in the gut.* “.

Checking for responses from people who tried it

“hmm…first time I took bif inf I started with small amount , part of a capsule, and got bellyache from it ( therapist had told me nobody ever gets bellyache from it, can given safely to babies…well, lets say i know my belly better then he does) ” [Phoenix Rising]

Bottom Line

The strongest evidence is for Lactobacillus rhamnosus with caution suggested for other Lactobacillus.

Streptococcus faecium and Streptococcus faecalis produce or not produce histamine depending on strain [1990] “Forty-one (31.5%) of the S. faecium strains and 2 (1.9%) of the S. faecalis strains produced histamine. ” [1988]

“the histamine producing strain Streptococcus thermophilus PRI60” [2014]

• So Streptococcus faecalis have a low risk of producing histamines.

Bifidobacterium (keep to the cited ones) appear promising (the ProBiota HistaminX has a lot of them in it).

There are a variety of sites, that gives lists of good and bad bacteria — unfortunately, they do not cite sources (or solid sources).

A reader wrote about this probiotic: ” with a special probiotic that i buy in Russia , i was having great results amazing “. He provided a link to it.

A research group at the First Moscow State Medical University has reported that they have identified a probiotic that eradicates eradicates small intestinal bacterial overgrowth (SIBO) in patients who also have irritable bowel syndrome (IBS).  The probiotic, available only in Russia, combinated four strains of bacteria and is named Florasan-D. Florasan-D includes a combination of Bifidobacterium bifidum,Bifidobacterium longum, Bifidobacterium infantis and Lactobacillus rhamnosus.

The findings revealed that both IBS-C and  IBS-D patients treated with the probiotic experienced statistically significant improvements in several measures (abdominal pain and stool frequency) after 28 days, compared with baseline.

Gut-Chek Blog

This did not cure SIBO/IBC-C/IBS-D. It improved it for some. He is likely one of the lucky ones. He is facing a problem because he is no longer able to buy it and asked for my help.

The research study is here (American Journal of Clinical Medicine Research, 2015 3 (2), pp 18-23.) And this chart may clarify “improves” and does not cure.

I was unable to find anything on the strains in this mixture nor their relative percentage. I found a Russian Reference that the dosage was 250 mg/day.

Replacement?

We are wishing the following:

• Bifidobacterium bifidum,
• Bifidobacterium longum,
• Bifidobacterium infantis and 
• Lactobacillus rhamnosus

CustomProbiotics

They have a 5 strain bifidobacteria containing the 3 above (with B. Lactis and B.Breve being the additional ones). They also sell pure Lactobacillus rhamnosus or use Culturelle (L. Rhamnosus GG).

They also have D-Lactate Free Probiotic Powder containing all of these, plus two more. IMHO — this would be my preferred substitution

• L. Rhamnosus, Strain LR-32 -MATCH
• L. Salivarius, Strain LS-33
• B. Lactis, Strain BL-04
• B. Bifidum, Strain Bb-06 – MATCH
• B. Infantis, Strain Bi-26 – MATCH
  
• B. Longum, Strain BL-05 – MATCH

Lifted Naturals Bifidus Mood Super Strains

This contains the same bifiobacteriums PLUS B. Breve and LGG.

Ingredients

L. rhamnosus (GG), B. longum, B. bifidum, B. lactis, B. breve, B. infantis

Bottom Line

In general, I do not recommend combinations probiotics because each species/strains has different impacts making the net effect fuzzy. Finding a reasonable replacement for the combination that helped this person is possible. My number 1 choice would be:

D-Lactate Free Probiotic Powder

Then Bifidus Mood Super Strains

Another interesting article showed up from AI detecting atypical articles on PubMed. I strongly suspect that this applies to noise sensitive individuals (
Hyperacusis). There are no studies on Hyperacusis microbiome

Effects of chronic noise on glucose metabolism and gut microbiota-host inflammatory homeostasis in rats. [2016]

 Chronic noise exposure increased blood glucose and corticosterone levels for at least 14 days after cessation of noise. Stressed rats also exhibited elevated levels of glycogen and triglyceride in the liver and impaired hepatic insulin production via insulin-induced insulin receptor/insulin receptor substrate 1/glycogen synthase kinase 3β signalling, which persisted for 3-14 days after cessation of noise exposure. Chronic noise altered the percentage of Proteobacteria and Actinobacteria in the gut, increasing Roseburia but decreasing Faecalibacterium levels in the cecum relative to controls. Immunoglobulin A, interleukin 1β, and tumor necrosis factor α levels were also elevated in the intestine of these animals, corresponding to noise-induced abnormalities in glucose regulation and insulin sensitivity. These results suggest that lifelong environmental noise exposure could have cumulative effects on diabetes onset and development resulting from alterations in gut microbiota composition and intestinal inflammation.

Effects of chronic noise on glucose metabolism and gut microbiota-host inflammatory homeostasis in rats. [2016]

• Chronic noise-exposure exacerbates insulin resistance and promotes the manifestations of the type 2 diabetes in a high-fat diet mouse model.[2018]
• Chronic noise stress-induced alterations of glutamate and gamma-aminobutyric acid and their metabolism in the rat brain. [2014]
• Effects of chronic noise on the corticotropin-releasing factor system in the rat hippocampus: relevance to Alzheimer’s disease-like tau hyperphosphorylation. “
  Chronic noise leads to long-lasting increases in the hippocampal CRF system and the hyperphosphorylation of tau in the hippocampus. Our results also provide evidence for the involvement of the CRF system in noise-induced AD-like neurodegeneration. “

Human Studies

 IL-12 levels increased, whereas the NKT cell population decreased with increasing noise levels. The results further suggested that cortisol levels are more influenced by the subject’s sensitivity to noise than to the level of chronic road traffic noise. Therefore, noise appears to have the largest effect on IL-12 levels as well as the population and activity of NKT cells. In conclusion, our results suggest that low-level road traffic noise and sensitivity to noise can affect health by causing changes in the immune response through mechanisms other than increased cortisol.

Effects of self-reported sensitivity and road-traffic noise levels on the immune system. [2017]

Exposure to noise in work environment increases the incidence of tension and inappropriate behavior associated with aggression. Controlling noise through use of protective equipment might reduce the deleterious effects of noise on workers.

Effect of Chronic Noise Exposure on Aggressive Behavior of Automotive Industry Workers. [2018]

• Blood Pressure of Jordanian Workers Chronically Exposed to Noise in Industrial Plants.[2017]
• Road traffic noise and hypertension–accounting for the location of rooms. [2014]

Note that hypertension(high blood pressure) is associated with these microbiome shifts

Bottom Line

I suspect there is a feedback cycle between the microbiome and
hyperacusis.

Looking at contributed samples that reported hyperacusis (some 73!), we see some significant patterns;

• Gammaproteobacteria 58/63 were low
• Lactobacillus 66/71 were low
• Eisenbergiella 42/54 were low

We do not know if the shifts caused the hyperacusis OR the hyperacusis caused the shifts OR there was a feedback cycle between the two,

The last post, we found that research had found the vitamin D was the key component for a cascade that influenced B Vitamins, sleep and some digestive issues. This post will try to address the issue of vitamin D dosage.

On my old web site, I had done several posts on Vitamin D (from 2005-2006) – with links to PubMed articles.

• Recommended Vitamin D Levels
• Vitamin D

In this post, I will jump to the bottom line fast (if you want more detail, see above).

Target Level

• “The patients with optimal vitamin D status [25(OH)D ≥75 nmol/l]  ” [2016]
• “Serum iPTH held a stable plateau level at 36 pg/ml as long as serum 25(OH)D values were higher than 78 nmol/l (31 ng/ml), but increased when the serum 25(OH)D value fell below this. ” [1997]
• “Evidence is reviewed that shows that serum 25(OH)D3 concentrations of < 80 nmol/L are associated with reduced calcium absorption, osteoporosis, and increased fracture risk.” [2004]
• In my posts from a decade ago, I created this chart using an image from an article from [2004]

My suggested target level is 120 nmol/l. 50% above the level that issues start.

How much to take?

This is easy if you know your current level due to a chart from 2004,

Find the best match in the chart. I will take the high lighted one:

• Actual reading: 66 nmol/l
• Chart target: 80 nmol/l
• Difference: 14 nmol/l
• Amount to take: 1371 IU
• So: 1371 IU/14 = 100 IU for each number below. Since our goal is 120 nmol/l, (120-66) * 100 = 5,400 IU/day

A reader indicated their level was 18 nmol/l. this becomes (120-18) * 100 = 12,000 IU/day.

Bottom Line

The numbers above are from the literature assuming no complicating factors such as those listed below. 

In these cases the dosages may need to be up to 10x more.

Any process resulting in malabsorption of intestinal fat may impair the absorption of vitamin D. In one study, absorption of tritium-labeled (3H)-vitamin D in normal subjects ranged from 62.4% to 91.3% of the initial oral dose (10). In patients with celiac disease, biliary obstruction absorption and chronic pancreatitis, absorption fell to 50%, < 28% and < 18% of the oral dose, respectively. In each case, impaired vitamin D absorption correlated with the degree of steatorrhea. Other conditions in which vitamin D absorption is impaired include liver failure (see below), cystic fibrosis, Crohn’s disease, and gastric bypass. Individuals taking bile acid-binding medications (such as colestyramine and colestipol for hypercholesterolemia) will also have impaired vitamin D absorption

Factors Influencing Vitamin D Status (2011)

The proper process is simple: Get your base line, do the computed amount above for 3 months, measure again. According to the literature you should be at the desired level by then. If you are 10% below, increase the dosage by 10%. This is the only way to estimate the degree of malabsorption.

Another interesting article popped out of the AI selected articles:

Vitamin D deficiency changes the intestinal microbiome reducing B vitamin production in the gut. The resulting lack of pantothenic acid adversely affects the immune system, producing a “pro-inflammatory” state associated with atherosclerosis and autoimmunity. [2016]

Vitamin D blood levels of 60-80 ng/ml promote normal sleep. The present study was undertaken to explore why this beneficial effect waned after 2 years as arthritic pain increased. Pantothenic acid becomes coenzyme A, a cofactor necessary for cortisol and acetylcholine production. 1950s experiments suggested a connection between pantothenic acid deficiency, autoimmune arthritis and insomnia. The B vitamins have been shown to have an intestinal bacterial source and a food source, suggesting that the normal intestinal microbiome may have always been the primary source of B vitamins. Review of the scientific literature shows that pantothenic acid does not have a natural food source, it is supplied by the normal intestinal bacteria.

Three months of vitamin D plus B100 resulted in improved sleep, reduced pain and unexpected resolution of bowel symptoms. These results suggest that the combination of vitamin D plus B100 creates an intestinal environment that favors the return of the four specific species, Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria that make up the normal human microbiome.

This lead to some related articles (also old)

It was found that the time after which changes in vitamin levels developed as well as the intensity of changes differ, depending on the experimental model used, but the sequence of vitamin disappearance from the organism is always the same. The first to disappear were vitamins B1, followed by vitamin B6 and pantothenic acid.

Changes in the levels of certain vitamins from B group under conditions of vitamin deficiency. 1976

• Decreased serum vitamin B₁₂ and vitamin D levels affect sleep quality in children with familial Mediterranean fever.[2018]

Bottom Line

From the above we see a cascade starting with deficient Vitamin D

1. Reduced Vitamin D
2. Reduced Thiamine (B1)
3. Reduced pyridoxine (B6)
4. Reduced Pantothenic Acid (B5)
5. eventually reduced Cobalamin (B12)
   1. ” affect VB12 level, indirectly, by reducing 25(OH)D level in middle aged women. ” [2018]

For CFS specifically we have Ana Dorothea Hoeck’s research

• Will vitamin D supplementation ameliorate diseases characterized by chronic inflammation and fatigue? [2011] (full text)
• A Review on the Potential Role of Vitamin D and Mineral Metabolism on Chronic Fatigue Illnesses 2016