“Do no harm” …unless it’s CFS

“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

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

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.

 

 

 

Reading Hopeful News reports and scientific reports

A reader forwarded me exciting news about lidocaine and positive results for CFS. The common term often used today is “Fake News”.  in many cases, the less severe “Misleading News” could be used. I prefer to use “hopeful news” – because the writing paints a future hope that may somehow be realized (and with 20 years seeing these hopes too often disappointed).

The article was in Spanish and is here. An english version on ProHealth states

  • “These results demonstrate that lidocaine injections reduce clinical fatigue of CFS patients significantly more than placebo, suggesting an important role of peripheral tissues for chronic fatigue. Future investigations will be necessary to evaluate the clinical benefits of such interventions.”

The actual study (full text is here). In reading any articles we look for things demonstrated:

  • To have statistical significance (CFS symptoms vary from day to day — was the change seen just happenstance? )
  • How many were positive results? negative results? no result?
  • How many items were measured and how?
    • Self-evaluation is very prone to suffer from placebo effects. Sugar pills improve many conditions!

Let us quote from the article:

“Fatigue ratings of CFS patients decreased significantly more after lidocaine compared to saline injections (p = 0.03). In contrast, muscle injections reduced pain, depression, and anxiety (p < 0.001), but these changes were not statistically different between lidocaine and saline (p > 0.05). ”

Ouch, fatigue rating — means self-perception. Lidocaine is a pain killer which is known to work. Reduction of pain usually results in less fatigue. Saline solution is not a pain killer. The alternative should have been an equivalent pain killing drug. Bad design! You may be testing pain killers not lidocaine!

The slight of hand is claiming “reduced pain, depression, and anxiety” — which BOTH saline and lidocaine did.  Saline doing short term pain relief etc is documented in this post with the main mechanism being improvement of blood flow (an anticoagulant effect). There was no difference between lidocaine, a saline solution and I suspect almost any anticoagulant — even plain aspirin. Another poor design choice. They claimed “This study used a parallel group, double-blind, placebo-controlled design.” Unfortunately, there was no placebo! Saline solution impacts CFS patients positively – Jen Brae can definitely confirm that in her own experience.

Some method notes:

  • “Ratings of overall fatigue, pain, and mood were obtained before and 30 min after the muscle injections” — so the conclusion is valid for exactly 30 minutes after injection. Whether there is any significant change the next day or week was not measured (or was not reported).
  • “that lidocaine was only more effective than saline in increasing mechanical pain thresholds at the shoulders but not at any other location.”
  • They cited using tables from a “Cohen” but there is no citation in the reference for a Cohen. Third party tables not done on CFS patients are very suspect — the metabolism of drugs by CFS patients can be very different than that of normal patients.
  • There was no breakdown of individual responses. “Averages” can be very deceitful (especially with small studies). A few very good responders can result in a major increase of the average. It may work for 10% and do nothing for 90%.
  • “The blood samples were immediately sent to the laboratory for analysis.” There was no mention of the results … did any lab results changed?
  • “These results demonstrate that lidocaine injections reduce clinical fatigue of CFS patients significantly more than placebo, suggesting an important role of peripheral tissues for chronic fatigue. Future investigations will be necessary to evaluate the clinical benefits of such interventions.” There was no Placebo…
    • “the injections you are going to receive contain either a local anesthetic or an inert substance”.  This is false — saline solution is not inert.

Bottom Line

Many readers forward me latest studies and ask for an analysis and comments. Why me?

  • I do not suffer from brain fog
  • I have been reading medical journals since I was 15 (part of a special enrichment program)
  • I have worked as a professional statistician and know how to take apart a study
  • I have been a high school general science teacher (and also chemistry and physics at College level)

This post tries to give a framework for less brain-fogged individual to work from (and hopefully challenge my readings and conclusion based on published evidence studies).

View of this Study

The people doing the study constructed it poorly. There is evidence that they are not well familiar with all of the prior related studies for CFS. There should have been scatter gram showing for individuals the before and after values for each measurement.

Should CFS patients ask for this based on the evidence in this study? No — the effect may last for only 30 minutes, one could easily speculate that common aspirin could have the same or better effect.

Let us look at stuff cited in an interview…

“Los investigadores anotaron que los hallazgos sugieren que los músculos y otros tejidos periféricos están involucrados en la fatiga crónica. Concluyeron que las inyecciones de lidocaína ayudaron a bloquear la señalización anómala de los metabolitos musculares.”

“The researchers noted that the findings suggest that muscles and other peripheral tissues are involved in chronic fatigue. They concluded that injections of lidocaine helped block abnormal signaling of muscle metabolites.”

They produced no lab results showing “abnormal signaling of muscle metabolites” before the injections or a change after the injections….  “Show me the beef! (evidence)”

 

 

Impact of additives and food on Herbs and Health

Updating my notes on Oregano today, I came across this study:

  • “Results showed that protein, pH, aw, presence of beef extract, sodium lactate and nitrates did not influence their antimicrobial effect. In contrast, the presence of pork fat had a negative effect against both [Garlic and Oregano] Essential Oils [EO] associated with their dilution of the lipid content.  The addition of food phosphates also exerts a negative effect against EOs ” [2017] A common source of pork fat are hot dogs and sausages.
  • [Potato] Starch and [sunflower] oils concentrations of 5% and 10% had a negative impact on the EO efficacy. On the contrary, the EOs were more effective at high concentrations of protein, and at pH 5, by comparison with pH 6 or 7. ” [2008]
  • ” EOs retained greater efficacy at pH 5 and 2.32% sugar…moderate levels of simple sugars.” [2009]

And from prior posts dealing with food additives:

  • ”geographical variation in Crohn’s Disease [CD] correlates with emulsifier consumption as does the increasing incidence of CD in Japan; … very small concentrations of the emulsifier polysorbate 80 enhance bacterial translocation across intestinal epithelia.” [2013] See this post for more and this one on Endocrine Disruptors.
    • ”we determined that the polysaccharide dietary additive, maltodextrin (MDX), impairs cellular anti-bacterial responses and suppresses intestinal anti-microbial defense mechanisms”[2015]
    • Avoid Emulsifers, (sometimes they are called “Conditioners” on labels) especially
  • “Findings from epidemiology studies indicate that diets high in animal fat and low in fruits and vegetables are the most common pattern associated with an increased risk of IBD. Low levels of vitamin D also appear to be a risk factor for IBD. …. Unfortunately, omega 3 supplements have not been shown to decrease the risk of relapse in patients with Crohn’s disease. … Although fiber supplements have not been definitively shown to benefit patients with IBD, soluble fiber is the best way to generate short-chain fatty acids such as butyrate, which has anti-inflammatory effects. Addition of vitamin D and curcumin [Turmeric] has been shown to increase the efficacy of IBD therapy. There is compelling evidence from animal models that emulsifiers in processed foods increase risk for IBD.” [2016]
  • dietary emulsifiers interact with the multilayered endogenus mucus secretaions that coat the luminal surfaces of the intestinal tract and may compromise the ability of the human mucus to prevent contact between microorganisms and intestinal epithelial cells. Because emulsifiers have become ubiquitous ingredients in virtually all processed foods and beverages, including many that claim to be “organic”… [2016]

Bottom Line

Processed food is likely a significant contributor to IBD/IBS/FM/CFS. Population study also associate non-Mediterranean diet pattern with higher incidence of IBD. Pork and using sunflower oil (use Olive oil instead) is likely a food to exclude from your diet if you are taking herbs or essential oils because they reduce the herbs effectiveness. Avoid foods that lists emulsifiers and phosphates. Keep a note on your smart phone of the name of the common emulsifiers listed above.

And Yes, “Virginia there are organic emulsifiers in organic food…. “ — avoid them. Organic does not mean unqualified safe or good.

mat

 

 

Diets for CFS/IBS/FM Microbiome

I have covered some diets in some prior post. Diets, like antibiotics and even supplements, are often toss at a patient without researching the potential side-effects. Having a disease model (microbiome shift) gives a measuring stick to evaluate suggestions against.


PubMed in 2017

Explicit Studies

So – existing literature has found little solution apart from some supplements which I have posted on earlier.

Looking at microbiome shifts

I was surprised not to find more on the various diets cited above, especially shifts in Firmicutes and Bacteroidetes. There was only a few high quality reports.

Ketogenic Diet

Mediterranean Diet (MDS)

  • Mediterranean diet and faecal microbiota: a transversal study.[2016]
    • Mediterranean Diet Score (MDS) was associated with a higher abundance of Bacteroidetes (p = 0.001), Prevotellacea (p = 0.002) and Prevotella (p = 0.003) and a lower concentration of Firmicutes (p = 0.003) and Lachnospiraceae (p = 0.045).  Also,  in subjects with MDS ≥ 4, higher concentrations of faecal propionate (p = 0.034) and butyrate (p = 0.018) were detected. ” 🙂 Perfect!

Mediterranean Diet Score

There is an interesting study looking at typical diet in 7 countries at this web site. From this 2012 study, you can evaluate where you are, and provide clues as to how to alter your general diet. My own score with below is a low 8, and I can see some changes that I can make to increase it.

mds

Bottom Line

No diet has been shown to have health benefits for CFS/FM/IBS apart from certain specific supplements.  On the other hand, if the microbiome shift model is correct, the Mediterranean Diet is likely to result in improve symptoms that will increase the higher you get your score. How? it will counter the shift of bacteria seen in CFS.

Nuts and Seeds for CFS?

A reader forwarded me a link to a paper and from some of his questions, I thought that I should explain the model that I am assuming for Lactobacillus

  • Supplementation with Lactobacillus probiotics is generally a poor choice….
    • Almost all probiotics with be 100% gone within 24 hours.
    • They do not take up residence — they are in transit only
    • They produce chemicals that are effectively natural antibiotics… unfortunately, the targets are often E.Coli and Bifidobacteria.
  • Taking supplements that encourages Lactobacillus (i.e. your own natural) and also biodiversity is assumed to be good.  Both criteria should be satisfied. The concept is that these lactobacillus are friendly to your specific strains of E.Coli and Bifidobacteria.
    • nut types that increases Firmicutes and decreases Bacteriodetes should likely be avoided[For new readers: CFS/IBS/FM have major increases of Firmicutes  and collapse of Bacteriodetes. See this post for background and studies].

Mediterranean/Greek Diet

This type of diet seems to be well suited for CFS/FM/IBS, I will review the literature in another post.

“Excesses of any component of the diet were typically avoided and consequently over-consumption was rare. Sugar, sweet desserts, and salt were rarely consumed, and animal products except for seafood and yogurt and cheese were less frequently consumed. In addition, olives and olive oil, nuts, and seeds were parts of daily intakes, as wine and spices often were. Balanced eating patterns of the macronutrients greatly reduced the development of overweight or obesity and metabolic diseases resulting from excessive caloric intakes. Intake percentages of fats and carbohydrates were fairly high, but total calories were not higher than maintenance requirements.” [2016 – full text]

Note: Beware of “mediterranean-like” diets that just tosses in some elements on top of a basic western diet.

Studies

  • “Changes in the Gut Microbial Communities Following Addition of Walnuts to the Diet” [2017]
    • “Walnuts are rich in omega-3 fatty acids, phytochemicals and antioxidants making them unique compared to other foods…Walnuts are an excellent source of omega-3 fatty acids, particularly alpha-linoleic acid. “
    • “Walnuts increased the abundance of Firmicutes and reduced the abundance of Bacteriodetes.” – this is the opposite of what we hope to do. See this post for background.
    • “The animals that ate walnuts had a significantly greater (>1.8 fold) ratio of Firmicutes to Bacteriodetes when compared to the replacement diet.”
  • “Prebiotic nut compounds and human microbiota. [2017]”
    • “After 6 weeks, significant increases in Bifidobacterium spp. and Lactobacillus spp. were observed in the almond and almond skin groups, although the populations of Escherichia coli showed little change, and the growth of Clostridium perfringens was significantly repressed.”
  • Effects of almond and pistachio consumption on gut microbiota composition in a randomised cross-over human feeding study.[2014]
    • “The effect of pistachio consumption on gut microbiota composition was much stronger than that of almond consumption and included an increase in the number of potentially beneficial butyrate-producing bacteria. Although the numbers of bifidobacteria were not affected by the consumption of either nut, pistachio consumption appeared to decrease the number of lactic acid bacteria (P< 0·05). Increasing the consumption of almonds or pistachios appears to be an effective means of modifying gut microbiota composition.”
      • Excessive lactic acid is a CFS characteristic, see this post.
  • Dairy and plant based food intakes are associated with altered faecal microbiota in 2 to 3 year old Australian children [2016].
    • “Dairy intake was positively associated with the Firmicutes:Bacteroidetes ratio, and in particular Erysipelatoclostridium spp., but negatively associated with species richness and diversity. ” – in other words, dairy shifts in the wrong direction — i.e. Yogurt may not be helping you
    • “In contrast, vegetarian protein (soy, pulses[Dried peas, edible beans, lentils and chickpeas are the most common varieties of pulses] and nuts) serve intake (FFQ data) was negatively associated with the relative abundance of the phylum Firmicutes” — so nuts (excluding walnuts cited above) shifts in the right direction.
    • “data revealed that the relative abundance of Bacteroidetes was negatively associated with dairy serve intake while the relative abundance of Firmicutes was negatively associated with vegetarian protein serve intake. “
    • Note that the full text associate certain foods with certain bacteria groups (plus and minus), and is worth reading if you have your uBiome done.
  • Prebiotic effects of almonds and almond skins on intestinal microbiota in healthy adult humans[2014].
    • ” Significant increases in the populations of Bifidobacterium spp. and Lactobacillus spp. were observed in fecal samples as a consequence of almond or almond skin supplementation. However, the populations of Escherichia coli did not change significantly, while the growth of the pathogen Clostridum perfringens was significantly repressed. “
  • “a moderate intake of almonds improves diet quality in adults and their young children and modulates microbiota composition.” [2016]

Bottom Line

Consumption of soy, pulses[Dried peas, edible beans, lentils and chickpeas] and whole nuts should assist correcting the microbiome shift seen with CFS, in general.

  • Do not include Walnuts.
  • Include pistachios daily
  • Almonds (Almond milk is not the same)
  • Restrict Dairy Intake
  • Peanut is NOT A NUT (see wikipedia)
    • Nothing found on peanut intake impact on the microbiome. Many studies on peanut allergies.
    • I am neutral if it is good or bad… no evidence to work from.

For the rest of the nuts, we do not have studies on specific varieties.

Zinc – What do we know in 2017

  • “We found that serum zinc was significantly lower in the CFS patients than in the normal controls. There was a trend toward a significant negative correlation between serum zinc and the severity of CFS and there was a significant and negative correlation between serum zinc and the subjective experience of infection.” [2006]
  • “Serum levels of zinc (P = 0.001) and magnesium (P = 0.002) were significantly decreased by FM groups,” [2008]
  • “[IBS]…Finally, the role of zinc in treatment of infectious diarrhea led to studies of its effect on intracellular human enterocyte ion secretion. ” [2010]
  • “The aim of our study was to evaluate the oral dietary intake of a group of patients with irritable bowel syndrome and to compare with international recommendations….A low intake of calcium, magnesium, yodo and zinc was detected.” [2004]
  • “paper reports a study of 50 patients affected by irritable bowel syndrome. Two subgroups have been identified (Ac and Ad), characterised by reduced blood zinc [correction of zinchemia] and increased fecal excretion of zinc. This finding suggests that the syndrome has a multifactorial pathogenesis and that over time it may follow a different pattern in the different subgroups.” [1990]
  • Dryness of eye symptom associated with low zinc levels [2016]

Other Aspects

  • “These studies demonstrate for the first time that zinc regulates LPS-mediated immune activation of human macrophages in a ZIP8-dependent manner, reducing IL-10. Based on these findings we predict that macrophage zinc metabolism is important in host defense against pathogens.” [2017]
  • “We found no evidence that the use of oral zinc supplementation improves symptoms in adults with tinnitus.” [2016]
  • “We can conclude that the food supplement containing α-lipoic acid, L-carnosin, zinc,[ 7.5 mg] and vitamins of group B improved glycemic control, lipid profile, and anti-oxidative stress markers.” [2016]
  • “The scientific evidence presented in this systematic review shows that zinc supplementation improves insulin resistance in obese individuals of both sexes.” [2017]
  • “35% to 45% of adults 60 years of age or older had zinc intakes below the estimated average requirement of 6.8 mg/day for elderly females and 9.4 mg/day for elderly males. Zinc deficiency may lead to loss of appetite, impaired immune function, weight loss, delayed healing of wounds, eye and skin lesions, and smell and taste disturbances” [2016]
    • Zinc supplementation at 30 mg/d for 3 mo is effective in increasing serum zinc concentrations in nursing home elderly; however, not all zinc-deficient elderly reached adequate concentrations.” [2016]

Missing Diet on what is an effective level of supplementation

Above we see low levels across the board. There have been no reported studies on the effect of supplementation in the above conditions. What is level and duration needed to be effective!

Bottom Line

This [2016] study seems the best match for CFS/FM/IBS and used 30 mg/d for at least 3 mo. “Tolerable Upper Intake Levels (UL) of zinc for people who are not receiving zinc under medical supervision: … adults 19 years and older (including pregnancy and lactation), 40 mg/day.” WebMd

Coenzyme Q10 in 2017

A reader requested to review the most recent literature on CoQ10 and summarize my conclusions.

Fibromyalgia and Migraines

“CoQ(10) level in plasma samples from FM patients was doubled compared to healthy controls and in blood mononuclear cells isolated from 37 FM patients was found to be about 40% lower….The protection caused in mononuclear cells by CoQ(10) would indicate the benefit of its supplementation in FM patients. ” [2009]

” Coenzyme Q(10) (CoQ(10)) levels in salivary cells (SCs) and mononuclear blood cells (BMCs) from Fibromyalgia (FM)..were reduced in both cell models. Oral supplementation showed an improvement in clinical symptoms and restored levels.” [2012]

” In this report, we show the effect of CoQ10 treatment on clinical symptoms, blood mononuclear cells, and mitochondrial and oxidative stress markers from a woman with FM. After CoQ10 treatment, the patient reported a significant improvement of clinical symptoms.” [2012]

“A placebo-controlled trial of CoQ10 in FM patients has shown a reduced NLRP3 inflammasome activation and IL-1β and IL-18 serum levels.” [2014]

  • “300 mg/day CoQ10 divided into three doses”
  • This study did not describe any symptom improvements seen — it was focused on lab results.
  • [2011] study cites: “Patients with CoQ(10) deficiency showed a statistically significant reduction on symptoms after CoQ(10) treatment during 9 months (300 mg/day).”

Folic Acid and coenzyme q10 ameliorate cognitive dysfunction in the rats with intracerebroventricular injection of streptozotocin [2012].

  • “The present results suggest that CoQ10 and folic acid have therapeutic and preventive effects on cognitive impairments in Alzheimer’s disease.”
  • [2006] study on mice, found CoQ10 alone had similar effects.

Role of magnesium, coenzyme Q10, riboflavin, and vitamin B12 in migraine prophylaxis. [2004] “

  • “The therapeutic potential of magnesium, coenzyme Q(10), riboflavin, and vitamin B(12) can be cautiously inferred from some published open clinical trials; it should, however, be considered that double-blind randomized larger studies are needed to correctly estimate the impact of the placebo effect in these promising therapies.”
  • “Treatment with … magnesium, riboflavin and Q10 ..had an impact on migraine frequency which showed a trend towards statistical significance.” [2015] i.e. it looks like it may help, but the effect could be random variation of patients symptoms.
  • Oxidative stress correlates with headache symptoms in fibromyalgia: coenzyme Q₁₀ effect on clinical improvement.[2012]
    • “induced a significant improvement in clinical and headache symptoms”

CFS/ME

No Studies Could be found for…

  • Small intestinal bacterial overgrowth
  • IBS

Bottom Line

A dosages of 300 mg/day of CoQ10 appears to have significant benefits. CoQ10 alone for CFS had no studies, only with NADH (which has benefits for CFS alone). NADH is related to niacin (B3) which may be a more economical supplement than NADH, but this is speculation as no studies have been done. NADH amounts cited in studies with positive effects was 20mg/day – but evidence suggests it benefits will disappear after 3 months.

I discovered a 2010 article finding that grapefruit juice significantly enhances the absorption of CoQ10

NADH Notes

  • “Administration of oral NADH was associated to a decrease in anxiety and maximum heart rate, after a stress test in patients with CFS. On the contrary, this treatment did not modify other clinical variables and the global functional performance.” [2010]
  • “8 of 26 (31%) responded favorably to NADH in contrast to 2 of 26 (8%) to placebo. ” [1999]
  • “The twelve patients who received NADH had a dramatic and statistically significant reduction of the mean symptom score in the first trimester (p < 0.001). However, symptom scores in the subsequent trimesters of therapy were similar in both treatment groups. ” [2004]