There is evidence suggesting that both lactose and gluten sensitivity may be the result of shifts in the microbiome. In this post I will explore gluten intolerance.

• “The Mayo Clinic reports that intestinal problems such as lactose intolerance  may be present long after the parasites are gone.”[src]

Pub Med Studies

• A commensal Bifidobacterium longum strain improves gluten-related immunopathology in mice through expression of a serine protease inhibitor [2017].
• “114 bacterial strains belonging to 32 species were isolated; 85 strains were able to grow in a medium containing gluten as the sole nitrogen source, 31 strains showed extracellular proteolytic activity against gluten protein and 27 strains showed peptidolytic activity towards the 33 mer peptide, an immunogenic peptide for celiac disease patients. ” [2017]
• Significantly higher faecal counts of the yeasts candida and saccharomyces identified in people with coeliac disease [2017].
  • “Candida sp. was detected in 33% of the CoeD group compared 0% of the control group (p = 0.000) and Saccharomyces sp. was detected in 33% of the CoeD group compared to 10% of the control group (p = 0.026).”
• Dysbiosis a risk factor for celiac disease. [2017]
  • “Celiac disease is associated with microbiota alteration, especially with an increase in the number of Gram-negative bacteria and a decrease in the number of Gram-positive bacteria. “

  • 

    From Wikipedia

• Changes in duodenal tissue-associated microbiota following hookworm infection and consecutivegluten challenges in humans with coeliac disease [2016].
  • ” Bacteroidia and Flavobacteriia (class) and Bacteroidales and Flavobacteriales (order) displayed a trend towards increased abundance in Trial subjects “
  • “Together, these data suggest that helminth infections and gluten exposure can significantly alter the composition of the tissue-resident and faecal microbiota, which has implications for the purported therapeutic efficacy of helminths in inflammatory disease.”
• Effect of Bifidobacterium breve on the Intestinal Microbiota of Coeliac Children on a Gluten Free Diet: A Pilot Study. [2016]
  • ” The comparison between CD subjects and Control group revealed an alteration in the intestinal microbial composition of coeliacs mainly characterized by a reduction of the Firmicutes/Bacteroidetes ratio, of Actinobacteria and Euryarchaeota. Regarding the effects of the probiotic, an increase of Actinobacteria was found as well as a re-establishment of the physiological Firmicutes/Bacteroidetes ratio. Therefore, a three-month administration of B. breve strains helps in restoring the healthy percentage of main microbial components.”
• “Conclusion. The probiotic formula[5 g of VSL#3 twice daily] when taken orally over the 12-week period did not significantly alter the microbiota measured in this population. ” [2016]
• The Overlap between Irritable Bowel Syndrome and Non-Celiac Gluten Sensitivity: A Clinical Dilemma [2015].
  • “While the treatment of non-celiac gluten sensitivity is exclusion of gluten from the diet, some, but not all, of the patients with IBS also improve on a gluten-free diet. “
• Intestinal microbiota modulates gluten-induced immunopathology in humanized mice.[2015]
  • ” Antibiotic treatment, leading to Proteobacteria expansion, further enhanced gluten-induced immunopathology in conventional SPF mice. Protection against gluten-induced immunopathology in clean SPF mice was reversed after supplementation with a member of the Proteobacteria phylum, an enteroadherent Escherichia coli isolated from a CD patient. The intestinal microbiota can both positively and negatively modulate gluten-induced immunopathology in mice. In subjects with moderate genetic susceptibility, intestinal microbiota changes may be a factor that increases CD risk.”
• Novel players in coeliac disease pathogenesis: role of the gut microbiota [2015].
  • “Several studies point towards alteration in gut microbiota composition and function in coeliac disease, some of which can precede the onset of disease and/or persist when patients are on a gluten-free diet. Evidence also exists that the gut microbiota might promote or reduce coeliac-disease-associated immunopathology. “
• “Approximately 30% of the general population carry the HLA-DQ2/8 coeliac disease susceptibility genes; however, only 2–5% of these individuals will go on to develop coeliac disease, suggesting that additional environmental factors contribute to disease development.^[2010]  “
• “Specifically, changes in the abundance of Firmicutes and Proteobacteria have been detected in children and adults with active coeliac disease.^42,43 Other studies have reported decreases in the proportion of protective, anti-inflammatory bacteria such as Bifidobacterium, and increases in the proportion of Gram-negative bacteria such as Bacteroides and E. coli, in patients with active coeliac disease.^44–46 Increases in the number of Staphylococcus^44,46 and Clostridium,^44,47 and decreases in Lactobacillus spp.^46,48,49 have also been reported in children with coeliac disease.” [2015]
• EFFECTS OF PROBIOTIC INTAKE ON INTESTINAL BIFIDOBACTERIA OF CELIAC PATIENTS[2017].
  • “Faecal bifidobacteria concentration before probiotic consumption was significantly higher in healthy individuals (2.3×108±6.3×107 CFU/g) when compared to celiac patients (1.0×107±1.7×107 CFU/g). “
  • “The probiotic supplementation significantly increased the number of bifidobacteria in the feces of celiac patients, although it was not sufficient to reach the concentration found in healthy individuals prior to its consumption.”

Bottom Line

The DNA risk of gluten sensitivity may exist in 30% of the population, however developing gluten sensitivity may be an epigentic event triggered by a shift in bacteria in the microbiome.

You have not become gluten/lactose sensitive — your microbiome has become gluten/lactose sensitive.

Correction of the microbiome shift appears likely to reverse the gluten sensitivity even with a DNA risk factor. We see studies suggesting that some bifidobacteria have a positive effect. Lactobacillus containing VSL#3 does not appear to be effective.  We do not know which families or strains are the problem (too high or too low is unclear).

The Dilemma: Going on a Gluten free diet does alter the microbiome. Does this change make it easier or harder to return to a healthy microbiome? Yes, it helps with symptom relief … but…

• “A number of taxon-specific differences were seen during the gluten-free diet: the most striking shift was seen for the family Veillonellaceae (class Clostridia), which was significantly reduced during the intervention (p = 2.81 × 10(-05)). Seven other taxa also showed significant changes; the majority of them are known to play a role in starch metabolism. We saw stronger differences in pathway activities: 21 predicted pathway activity scores showed significant association to the change in diet. ” [2016]

A frustrated reader wrote

“Hi, Ken. I am diagnosed with CFS, FM, MCS, LYME DISEASE and I am celiac. I have read your article about taking lactobacillus and CFS. However, in my case I have very low lactobacillus and can not raise them. I also have high clostridium species  but not clostridium difficile . I have done several treatments based on antibiotics selective only for the intestine – intestinal dysfunction.  I am not having results with suppositories based on natural herbal extracts that a naturopath friend from Germany brings me.

I’m still the same. I have taken probiotics only with lactobacillus -Ther Biotic Factor 1- and now I am with ther- Biotic complete. I would like to know your opinion. I have been testing different probiotics for 5 years without any results. A million thanks”

To start, supplementing with lactobacillus probiotics will not cause your lactobacillus to increase. Most lactobacillus probiotics do not take up residency. They will just hang around for a few hours and be gone — see this post for studies. This issue is made more complex because while they are in your system for a few hours, they will also be killing off bacteria families that you are low in.

You have to encourage the remnants of your own lactobacillus to grow.  There are several ways that may be needed:

• [ROTATE] Killing off the bacteria that kills off the Lactobacillus…  At present, I would suggest as a (gentle) starting point:
  • Myrrh  and boswellia (frankincense) gum
    • As “tears” that are chewed as a gum is my preference
  • Neem
    • As capsules or as a tea
  • Licorice
    • Spezzatina is my preference
• [CONTINUOUS] Providing suitable foods (that we know are missing in CFS patients because the bacteria producing these metabolites have been devastated)
  • B-12, Methylcobalamin – 1000 mcg/day
  •  CoQ10   300mg/day – ideally with a few ounces of Grapefruit juice.
  • B9 as Folinic Acid (the bioactive form) 1000 mcg/day
  • Personal Note: After doing the above post, I started taking precisely what was suggested. While fully recovered from CFS, I had residue severe psoriasis on my heels with very deep cracks. Within two weeks, the cracks disappeared and the heels have been growing healthier every week.
    • WARNING: Some people can respond with severe anxiety, see this external post.
  • Vitamin D3 – 15,000 IU/day see this post for it’s impact on Vitamin B production
• [ROTATE] Population by probiotics known to take up residency (and thus can start making the environment friendlier to lactobacillus)
  • E.Coli probiotics are my first choice.
    • Mutaflor – a comment reads “After trying a number of suggested supplements, I wasn’t expecting much but mutaflor resulted in a complete symptom remission in only 3 days with no herx reaction. I thought I was cured but, sadly, after about a month mutaflor’s effectiveness dropped to almost nothing. “
    • Symbioflor 2: see this post for some readers’ experience
  • Bifidobacterium probiotics (with no lactobacillus) see this post for what’s available and relative costs

My model is simple to understand: “There is a shift across dozen of bacteria families — the shifted (bad) families cross support each other making it hard to undo. Some item X may reduce 90% of dominant (bad) species, resulting in apparent remission — but the remaining 10% become resistant and slowly regrow — resulting in a relapse. You have to slowly repopulate across multiple good bacteria families until they are able to keep the bad bactera in control (ideally evict them).”

This means that you need to keep rotating herbs, spices, probiotics, antibiotics, at least every two weeks (every week is fine!). The 10% that survived week#1 are unlikely to survive a different antibacterial that uses a different mechanism. You may be down to 1% — but 1% can still regrow… so it is constant rotation even after symptoms disappears. You may later go to one week on and 1-2 weeks off; keeping a close monitor on symptoms.  Mutations will cause resistance constantly — thus you must keep ahead of the mutations by constant changing of antibacterials.

Bottom Line

I do not have a treatment plan or a protocol.  I have a model. I also consolidate clinical results from PubMed.  My goal is to just provide a list of candidate substances to try (in discussion with your knowledgeable medical provider) which are more likely to help than randomly trying things.  These candidate substances are also consistent with the model, for example —

• Low B12 –> no/low Lactobacillus Reuteri (which produces B12) –> verified from lab results
• Low B9 –> no/low Bifidobacteria (which produces B9) –> verified from lab results
• Low Vitamin D3 –> low production of B vitamins

Many gums or resins from trees have favorable profiles. One of my favorite is greek mastic gum which you can buy raw and chews just like a gum. It reduces bacteria in the mouth and do a ton of healthful things. I have a strong preference to medications that have been used successfully for thousands of years over newly developed drugs with unknown risks for long term use, and sometime short term use.

“The Jerusalem Balsam, a remedy based on an ethanolic extract of a herbal mixture, was formulated in 1719 in the pharmacy of the Saint Savior monastery in the old city of Jerusalem… one of the formulas, found in a manuscript form in the archive of the monastery, contains four plants: olibanum (Boswellia spp.), myrrh (Commiphora spp.), aloe (Aloe sp.) and mastic (Pistacia lentiscus L.). We conducted pharmacological assays on this four-plant formula. It showed anti-inflammatory, as well as anti-oxidative, and anti-septic properties.” [The Jerusalem Balsam: from the Franciscan Monastery in the old city of Jerusalem to Martindale 33. 2005]

Also see:  Medieval Pharmacotherapy Continuity and Change Case Studies from Ibn Sına and some of his Late Medieval Commentators [2009 – Full Book 815 pages]

“The most promising plant and herbal products [for inflammatory bowel disease] were tormentil extracts, wormwoodherb, Aloe vera, germinated barley foodstuff, curcumin, Boswellia serrata, Panax notoginseng, Ixeris dentata, green tea, Cordia dichotoma, Plantago lanceolata, Iridoidglycosides, and mastic gum. ” [2016]

• The most important clinical trials conducted [ in inflammatory bowel disease] so far refer to the use of mastic gum, tormentil extracts, wormwood herb, aloe vera, triticum aestivum, germinated barley foodstuff, and boswellia serrata. …boswellia serrata gum resin and plantago ovata seeds were as effective as mesalazine, ” [2015]
• “Taken together, allergic reactions to Christmas tree, poinsettia, Christmas cactus, perfumed candles, Christmas typical food, common gifts like mobile phones and laptops, frankincense, myrrh and pollens have been described but in very rare instances. ” [Christmas from an allergist’s perspective 2016].

The “tear form” which is chewed like gum (unlike powder in capsules) and then swallowed have several advantages:

• Reduce bacteria in the mouth (a likely reserve of bacteria that may repopulate the gut) and greatly improve mouth health!
• Allows the active compounds to enter the body via the sublingual route
• Impacts the entire digestive system.

The first question many people may have is “Where do I get these tears?”. I recently discovered an Online shop in Greece that sells all of these tears: YouHerbIt.

Suggested use: Use one for a week and then rotate to the next.

Mastic Gum

• Review: Chios mastic gum: a plant-produced resin exhibiting numerous diverse pharmaceutical and biomedical properties.[2012]
  • “eradication of bacteria and fungi that may cause peptic ulcers, tooth plaque formation and malodor of the mouth and saliva; (b) amelioration or dramatic reduction of symptoms of autoimmune diseases by inhibiting production of pro-inflammatory substances by activated macrophages, production of cytokines by peripheral blood mononuclear cells in patients with active Crohn’s disease, and suppression of production of inflammatory cytokines and chemokines in an asthma model in mice; “
  • Anti-inflammatory activity of Chios mastic gum is associated with inhibition of TNF-alpha induced oxidative stress.[2011]
  • Antiinflammatory and antioxidant activities of gum mastic [2010].
• Antimicrobial Effects of Mastic Extract Against Oral and Periodontal Pathogens[2017].
  • Mastic extract led to significantly (P ≤0.016) increased inhibition of the tested periodontal pathogens((Porphyromonas gingivalis,  Streptococcus oralis, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Prevotella intermedia, and Prevotella nigrescens) ) compared with H₂O_{2(Hydrogen Peroxide)}. No effect of mastic extract was observed on Streptococcus mutans”.
  • “Three weeks use of all mastic gums resulted in a significant drop in the number of Mutans streptococci in the saliva. ” [2014]
  • “Ethyl acetate I. viscosa extract and total mastic extract showed considerable antimicrobial activity against oral microorganisms(Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Parvimonas micra). and could therefore be considered as alternative natural anti-infectious agents.” {2014]
• Chemical Composition of the Essential Oil of Mastic Gum and their Antibacterial Activity Against Drug-Resistant Helicobacter pylori. [2014]
• Effects of Chios mastic gum on cholesterol and glucose levels of healthy volunteers: A prospective, randomized, placebo-controlled, pilot study (CHIOS-MASTIHA) [2016].
  • ” has a significant lowering effect on total cholesterol and glucose levels of healthy volunteers, with excellent tolerance and no detectable side effects, especially in overweight and obese individuals.”

Boswellia Serrata/Frankincense gum resin [Commiphora…]

“The gum resin of Boswellia serrata (BS), a traditional treatment of Ayurvedic medicine in India also identified as Indian frankincense, Salai Guggal, or Indian olibanum, has been used for centuries as a remedy for many health problems [1996].”

• Boswellic Acid Improves Cognitive Function in a Rat Model Through Its Antioxidant Activity: – Neuroprotective effect of Boswellic acid [2017].
• “Our results suggest that frankincense should be further investigated for its promising potentiality to modulate not only inflammation/oxidative stress but also immune dysregulation, but attention should be paid to the composition of the commercial extracts.” [2017]
• ” For Crohn’s disease, the supplements for which clear benefits occurred in at least 2 studies were allopurinol, Boswellia serrata (frankincense or shallaki), Artemesia species (wormwood), Tripterygium wilfordii (léi gōng téng), and omega-3 fatty acids. ” [2017]

Myrrh Gum [Commiphora… ]

• Mechanisms on spasmolytic and anti-inflammatory effects of a herbal medicinal product consisting of myrrh, chamomile flower, and coffee charcoal[2017].
• Antispasmodic effects of myrrh due to calcium antagonistic effects in inflamed rat small intestinal preparations[2015].
  • “The resulting reduction of intestinal motility and spasmolytic effects provide a rationale for the symptom treatment of intestinal disorders such as irritable bowel syndrome.”
• Efficacy and safety of a herbal medicinal product containing myrrh, chamomile and coffee charcoal for the treatment of gastrointestinal disorders: a non-interventional study [2015].
  • “However, in the IBS group, monotreatment with the herbal preparation resulted in a significantly better outcome ..”
• A Combined Water Extract of Frankincense and Myrrh Alleviates Neuropathic Pain in Mice via Modulation of TRPV1 [2017].
• A Review of Anti-inflammatory Terpenoids from the Incense Gum Resins Frankincense and Myrrh [2017].
• Myrrh attenuates oxidative and inflammatory processes in acetic acid-induced ulcerative colitis [2016].
• “Myrrh extract showed inhibition of E.faecalis equal to that of 2% Chlorhexidine  followed by Neem, Liquorice and Saline.” [2016] –Note Neem and Liquorice are in my usual recommendation.
• “This study supports the possible use of essential oils from the Bursecaceae family[Boswellia, Myrrh…] in reduction and elimination of Candida spp. populations in patients with oral cavity fungal infections.” [2016]

On one of the facebook groups I followed, a member indicated remission/major improvement and gave some details in a post.

• ” Well it went better than I expected as I discovered a little known gem that resolved ALL of my metabolic related issues in 1 month and I felt GREAT!!”

When some reports come across my screen, I like to explore them to see if there is a sound basis for improvement (or a RISK to others). It may work for a small group of patients, but not for most. Alternatively, there may be a risk to the pocket book (i.e. someone indirectly/cleverly selling something).

The Magic?

“1,000 mcg a day [of chromium picolinate] is the magic number not 600. Combine the chromium with CLA [Conjugated Linoleic Acid]”

Chromium Picolinate

Some risks at 1000 mcg, low risk — but for the sake of full disclosure.

• “The only adverse effects of chromium picolinate I’ve read about occurred in isolated cases. In one, a woman who took 1,200 to 2,400 mcg daily over four to five months developed kidney failure and impaired liver function. In another, kidney failure occurred five months after taking 600 mcg of chromium picolinate daily for six weeks. And, a healthy 24 year old man reportedly developed reversible, acute renal failure after two weeks on a supplement that contained chromium picolinate as the main ingredient.” [Dr.Weill]
• “Chromium is LIKELY SAFE for most adults when taken by mouth, short-term. Up to 1000 mcg/day of chromium has been used safely for up to 6 months.

  Chromium is POSSIBLY SAFE for most adults when taken by mouth for longer periods of time. Chromium has been used safely in a small number of studies using doses of 200-1000 mcg daily for up to 2 years. Some people experience side effects such as skin irritation, headaches, dizziness, nausea, mood changes and impaired thinking, judgment, and coordination. High doses have been linked to more serious side effects including blood disorders, liver or kidney damage, and other problems. It is not known for sure if chromium is the actual cause of these side effects.” [WebMd]

CFS/IBS/FM

Only a single significant reference, but an interesting one!

• “The low Nickel (Ni) diet induced a significant and constant improvement of gastrointestinal symptoms and an equally significant improvement of visual analogue scale [in IBS]. Mean urinary output of ⁵¹Chromium ethylene-diamine-tetra-acetate (⁵¹Cr-EDTA) was 5.91%/24 hr (± 2.08), significantly different from the control group (2.20%/24 hr ± 0.60, P < 0.0001).”
• What to avoid in the low Nickel Diet is described in this PubMed article [2013]. The items to avoid are also the items in the Mediterranean Diet. Ugh. This article does mention “Vitamin C, orange juice, tea, coffee, milk inhibit nickel absorption in human[34]” As a side note, the shift of diet would induce a microbiome shift — so it may not be nickel that’s the issue, rather nickel is incidental (right treatment — wrong attribution).

Microbiome

• Intense Exercise and Aerobic Conditioning Associated with Chromium or L-Carnitine Supplementation Modified the Fecal Microbiota of Fillies[2016]. 
  • “chromium or L-carnitine induced moderate changes in the fecal microbiota of fillies”

Coagulation

• “Sodium chromate inhibits platelet function in vitro. ” [1970]

General

• “Additionally specific selected nutritional compounds, e.g. calcium, chromium, folate, PUFAs, vitamin D, B12, zinc, magnesium and D-serine have been postulated to be used as ad-on strategies in antidepressant treatment. In this context, dietary and lifestyle interventions may be a desirable, effective, pragmatical and non-stigmatizing prevention and treatment strategy for depression.” [2015] This list matches the pattern that I am advocating for CFS, implying that chromium is a reasonable choice.
• Chromium supplementation for adjuvant treatment of type 2 diabetes mellitus: Results from a pooled analysis.[2017]
  • “notably favorable effects were presented in T2DM subjects ingesting chromium chloride and chromium picolinate formulations.”
• NON-PHARMACEUTICAL INTERVENTION OPTIONS FOR TYPE 2 DIABETES: Diets and Dietary Supplements (Botanicals, Antioxidants, and Minerals)[2014].
  
  • “this meta-analysis of RCTs showed no effect of chromium on glucose or insulin concentrations in non-diabetic subjects, and data for persons with diabetes are inconclusive.”
  • “these studies suggest that the form of chromium influences the study results, and that the picolinate form provides greater efficacy”
  • ” recent study has found that chromium picolinate (500 and 1000 μg daily for 6 months) was ineffective at reducing HbA1c in obese, poorly-controlled, insulin-dependent individuals with T2D”

Conjugated Linoleic Acid

CFS/IBS/FM

• “Dietary CLA-supplementation upregulated colonic PPAR gamma expression and contributed to delaying the onset of experimental Irritable Bowel Disease “
• “Supplementation of CLA in the diet before the induction of colitis decreased mucosal damage” [2002]

Microbiome

• Conjugated Linoleic Acid Production by Bifidobacteria: Screening, Kinetic, and Composition[2016].
  • So Bifidobacteria (which CFS patients are often very low in), produces this
• “Moreover, bifidobacteria have been associated with the production of a number of potentially health promoting metabolites including short chain fatty acids, conjugatedlinoleic acid and bacteriocins. ” [2016]
• “Our data show that CLA are able to modulate stomach protein expression and exert a prebiotic effect on specific gut bacterial species.” [2015]
  • Lowered Firmicutes and increased Bacteroidetes (and huge increase in Verrucomicrobia)  — desired direction of shift
• The effect of drinking milk containing conjugated linoleic acid on fecal microbiological profile, enzymatic activity, and fecal characteristics in humans.[2007]
  • “no differences could be attributed to consumption of the different CLAs.”
  • Note: milk (lactic acid production) may be impacting the CLA.

Coagulation

• “the blood-clotting parameters and in vitro platelet aggregation showed that adding 3.9 g/d of dietary CLA to a typical Western diet for 63 d produces no observable physiological change in blood coagulation and platelet function in healthy adult females. Short-term consumption of CLA does not seem to exhibit antithrombotic properties in humans.” [2001]

Bottom Line

Taking B12 supplements because of low/no Lactobacillus Reuteri  in CFS Patients (the producer of B12 in humans) improves CFS symptoms. Since CLA is produced by bifidobacteria (also low in CFS patients), supplementing with CLA may have similar benefits for CFS Symptoms. Unfortunately, there are no studies testing this in actual patients. I would give CLA as a thumbs-up as a potential supplement without clear evidence (but no apparent risk).

Chromium supplementation is much trickier because there is a low risk factor involved. If you are diabetic or pre-diabetic, consult with your MD. There is no clear evidence that it  will help (nor that it would hurt). I have no recommendation on this.

“The path to CFS Patients’ Hell is paved with physician’s best intentions”. A few days ago, I was pinged by an old friend who was working with Rich Van Konynenburg, Ph.D, before his sudden death in 2012. In the subsequent years, she has suffered ‘consequences’ from some physicians who attempted to treat her.

This post looks at why CFS patients should ask for (demand) evidence based studies behind any recommendations from physicians.

Her current state:

• Low serum immunoglobulin M  (Igm) – aka  hypogammaglobulinemia (almost 8000 articles on PubMed)
  • “The spleen, where plasmablasts responsible for antibody production reside, is the major site of specific IgM production.”
• Low B cells (a lymphocyte not processed by the thymus gland, and responsible for producing antibodies.)
  • ” cells mature in the bone marrow, which is at the core of most bones.”
• And to add severe pain to the mixture — shingles that is not responding to antivirals.
  • The two items above results in patients catching infections easily (unlike the typical CFS patient who almost never get sick)

How much of this is seen with CFS?

The answer is a big yes — for those CFS patients that have had rituximab therapy. Whether this person had this therapy, or some other treatment that caused the same consequence is immaterial

• “We have previously suggested clinical benefit from B-cell depletion using the monoclonal anti-CD20 antibody rituximab in a randomized and placebo-controlled study [for CFS]. ” [2016]
  • Diagnostic and therapeutic considerations in patients with hypogammaglobulinemia after rituximab therapy [2017].
    • “infection rates are higher in rheumatic disease patients who develop hypogammaglobulinemia than those who do not. “
  • Suppression of normal immune responses after treatment with rituximab. [2016]
    • “we recommend that all patients who undergo rituximab therapy have baseline IgG, IgM, and IgA measurements and also have immunoglobulin levels monitored periodically during treatment.”
  • “We investigated whether B cell depletion and hypogammaglobulinemia that occur during  rituximab RTX treatment increase the risk of chronic SA nasal carriage and subsequent disease flares, ” [2015]

CFS Literature on rituximab

• “Unless there is enough evidence for neuroinflammation, aggressive immunotherapies like rituximab should not be considered. ” [2017]
• ” The use of rintatolimod and rituximab as well as counselling, behavioural and rehabilitation therapy programs may be of benefit for CFS/ME, but the evidence of their effectiveness is still limited.” [2017]
• “Clinically significant responses were seen in 18 out of 28 patients (64%) receiving rituximab maintenance treatment. For these 18 patients, the mean response durations within the 156 weeks study period were 105 weeks in 14 major responders, and 69 weeks in four moderate responders. ” [2015] – so the improvement is temporary!
• “defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67%) in the Rituximab group and in two out of 15 patients (13%) in the Placebo group (p = 0.003).  Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8-44). ” [2011]  so the improvement is temporary!
• ” Patients 1 and 2 had major amelioration from 6 weeks after intervention, patient 3 slight improvement from the same time, but then improved markedly from 26 weeks after intervention. The symptomatic effect lasted until weeks 16, 18 and 44, respectively. ” [2009]

Recovery Options

• “Intravenous immunoglobulin (IVIG) replacement therapy is the treatment of choice for most primary B-cell disorders with hypogammaglobulinemia,” [emedicine] duration is often for 1 year…
• Going back over a half century, I found the “old treatment”
  • • Hypogammaglobulinaemia, steatorrhoea and megaloblastic anaemia. Response to gluten-free diet and folic acid. [1962]
      • “Thus it seems probable that the gluten-induced enteropathy and perhaps folic acid deficiency rather than simple
        lack of vitamin B12 were the factors responsible in this instance.” Recovery duration was about 2 years.

Bottom Line

This is one example of a sad pattern that I have seen time and again. Treatment is advocated with a blinkered happy outlook (at work, we say “we’ve been popping happy (case) pills!”) ignoring the adverse cases. Often it ends up being viewed as 6 improved (statistically), 3 had no effect and 1 is worse.  How much worse is immaterial when physicians are popping optimistic pills. A marginal improvement of 6 people seems to be more important than severe long term damage to just 1 patient.

This problem is made far worse because patients are suffering from brain fog. Asking the physicians to produce the studies that they are basing their protocol on is essential. The studies should be on humans and clear. If you cannot understand the studies, feel free to forward them to me for an independent opinion.