Pain, Herbs, Spices, Supplements

A reader wrote about constant pain. One common cause of pain in FM is low oxygen level – typically caused by one or more of the following:

  • Vasoconstriction (narrowing of blood vessels, reducing oxygen delivery volume)
  • Fibrin deposits (blocking access of the blood’s oxygen into tissue)
  • Coagulation (thick blood) – blood moves slower, so less oxygen is delivered.

Some literature:

Vasodilators

I have often taken a vasodilator. Brain fog and the occasion pain disappeared. Which one, flushing niacin, which often create a major flush on occasion still. Unfortunately, the reader is unable to take niacin. The following are alternatives, my first choice would be 800 mg of magnesium per day, while slow — magnesium is reported to improve fibromyalgia [1995]

  • L-arginine is an amino acid that is a vasodilator. According to studies, it is higher in urine of CFS patients[2006], but is generally low  [1993]. It also shifts the Firmicutes-to-Bacteroidetes ratio to favor Bacteroidetes [2014] which unfortunately is the same type of shift seen in CFS “a higher relative abundance of Bacteroidetes and lower abundance of Firmicutes observed in ME/CFS patients compared to healthy controls.” [2015]
  • ” It is suspected that the cerebral vasodilator effects of Danshen and Gegen produced either on their own or in combination, can help patients with obstructive cerebrovascular diseases.” [2014]
  • Long-term intake of rosemary and common thyme herbs inhibits experimental thrombosis without prolongation of bleeding time [2008]. “both rosemary and common thyme significantly inhibited platelet reactivity and enhanced the flow-mediated vasodilation.”
    • “Common thyme and rosemary showed significant antithrombotic activity in vitro and in vivo. Neither herb affected flow-mediated vasodilation.” [2005]
  • Chakalaka-induced vasodilatation in patients with chronic myeloid leukaemia on tyrosine kinase inhibitors [2009]. Chakalaka is a South African vegetable relish,
  • ” our study confirmed the functional effects of fennel derived-nitrites using in vitro and ex vivo models that describe the promotion of angiogenesis, cell migration, and vasorelaxation.” [2012]
  • ” the effects of a dietary supplement containing β-hydroxy-β-methylbutyrate (HMB), glutamine and arginine on endothelial-dependent vasodilation of older adults…revealed a 27% increase in flow-mediated dilation among the treatment group” [2016]
  • “The current meta-analysis, therefore, does not provide unambiguous evidence to support the use of fat-soluble vitamin supplements (Vitamin D and E) to improve fasting flow-mediated vasodilation in adults.” [2015]
  • Garlic-derived polysulfides stimulate the production of the vascular gasotransmitter hydrogen sulfide (H2S) a… which induce smooth muscle cell relaxation, vasodilation, and BP reduction.” [2014]
  • Some sites mention [source] [source]
    • Catuaba Catuaba, Erythroxylum catuaba
    • Cayenne Pepper Cayenne Pepper, Capsicum minimum
    • Ginger Root Ginger Root, Zingiber officinale
    • Ginkgo biloba Ginkgo biloba, Ginkgo biloba L.
    • Gotu Kola Gotu Kola, Centella asiatica (L.)
    • Jiaogulan Jiaogulan, Gynostemma pentaphyllum
    • Lemon Balm
    • Lotus Lotus, Nelumbo nucifera
    • Nettle
    • Olive Leaf
    • Orange Orange, Citrus sinensis, Citrus spp.
    • Parsley Parsley, Petroselinum crispum
    • Schisandra Schisandra, Schisandra chinensis
    • Skullcap
    • Valerian
    • “According to Linus Pauling Institute, magnesium supplement at a dose of 730 milligrams per day can cause a 12-percent improvement in the normal dilation response of arteries. ” [source]

Fibrin Removers

Back in 2012, I did a series of posts on those available as supplements

All of these also increases penetration of antibiotics into tissue (up to 10x higher concentrations).

Coagulation (thick blood)

This is more complex, this post lists some items.

 

 

Black Walnut Leaf

As with my last post, I have not done a specific post on black walnut leaf (Juglans nigra). It was cited as reducing peroxynitrite which is suspected to cause environmental illness/multiple chemical sensitivity.

  • “the most valuable and cited medicinal plant species [for dental problems] used by the traditional drivers are Juglans regia”[2016]
  • “The medicinal plant species with highest fidelity level was of  … Juglans regia … each cited 100% for ..easy digestion …” [2016]
  • “The essential oils from three different samples of. J. nigra contained (E)-caryophyllene (17.3%-20.4%) and germacrene D (7.1%-22.5%) with smaller amounts of juglone (1.0%-8.8%), alpha-hydrojuglone (1.0-9.5%), and delta-cadinene (3.8%-8.7%). J. regia leaf oil, devoid of juglone, showed allelopathic activity, while J. nigra leaf oil was less phytotoxic.” [2013]
  • “The essential oil and its major components exhibited broad spectrum inhibition against all the bacterial strains with Gram-positive(Staphylococcus epidermidis MTCC-435, Bacillus subtilis MTCC-441, Staphylococcus aureus) being more susceptible to the oil than Gram-negative bacteria.(Proteus vulgaris MTCC-321, Pseudomonas aeruginosa MTCC-1688, Salmonella typhi, Shigella dyssenteriae, Klebsiella pneumonia and Escherichia coli).” [2012]
  • Walnut leaves selectively inhibited the growth of Gram positive bacteria, being B. cereus the most susceptible one (MIC 0.1mg/mL). Gram negative bacteria and fungi were resistant to the extracts at 100mg/mL.” [2007]
  • “The zones of inhibition due to the … Juglans regia leaf extracts ranged from 17.6 mm against P. acnes, 15.7 mm against S. aureus and 15.5 mm against S. epidermidis, respectively….These zones of inhibition were… less… to those obtained from doxycycline or clindamycin…. may be beneficial in treating acne especially when they are known to have anti-inflammatory activities. ” [2005]
  • “derum (Juglans regia; walnut tree) …The most sensitive organisms were A. viscosus, followed by S. mutans, S. salivarius, with L. casei being the most resistant.” [2006]

Bottom Line

Black Walnut Leaf (actually Walnut Leaf) is far more effective against a variety of Staphylococcus than the Lactobacillus tested. Folklore from tribal area in India and Pakistan had it helping with digestion and with bad teeth bacteria.

It continues to be in the recommended list of herbals.

Note: There are no studies for FM/CFS/IBS.

 

Pau D’Arco for CFS

Pau D’Arco (Tabebuia spp) was cited by a reader in a recent post. I had listed it in my post for herbs for treating CFS in 2015 but have not done a post focused on it. β-Lapachone (β-LAP) is a major part.

Bottom Line

Pau D’Arco (Tabebuia spp) continues to be acceptable list for the following reasons:

  • Does not inhibit Lactobacillus or Bifidobacterium.
  • Minor effect against E.Coli
  • Effective against S. aureus – which is implicated as being a significant bacteria with CFS (see this earlier post).
  • Effective against Candida

Note: No PubMed studies with CFS/FM/IBS were found. There are many some forum posts indicating it helps with candida.

Pau d’arco. While herbalists do use pau d’arco for CFS treatment, it hasn’t proven to be very effective. People on blood-thinner medications should not take pau d’arco.” [source]

Caprylic Acid Supplementation

In my last post, a reader cites taking caprylic acid or octanoic acid which I have not covered yet in any post.

  • “Taken together, these results indicate that combined treatment with low concentrations of caprylic acid and citric acid, which are of biotic origin, can eliminate microorganisms from unpasteurized carrot juice.” [2015]
  • “The levels of medium-chain fatty acids (MCFAs: pentanoate, hexanoate, heptanoate, octanoate and nonanoate), and of some protein fermentation metabolites, were significantly decreased in patients with CD, UC and pouchitis.” [2015]
  • “the 4 fatty acids : caproic acid, caprylic acid, capric acid and lauric acid in vitro. All four inhibited not only the mycelial but also the yeast-form growth of Candida albicans. In particular, capric acid and caprylic acid inhibited Candida mycelia growth at very low concentrations.”
  • “The data indicate that exposure to lauric acid (C12) was the most inhibitory to growth [of Clostridium difficile] (P<.001), as determined by a reduction in colony-forming units per milliliter. Capric acid (C10) and caprylic acid (C8) were inhibitory to growth, but to a lesser degree.” [2013]
  • Caprylic Acid reduces enteric campylobacter colonization in market-aged broiler chickens but does not appear to alter cecal microbial populations [2010].
  • “Results indicated that caprylic acid, monocaprylin, and sodium caprylate could potentially be used to treat Dermatophilus congolensis infections.” [2011]
  • Antibacterial effect of caprylic acid and monocaprylin on major bacterial mastitis pathogens [2005].

Clear impact on Lactobacillus, Bifidobacteria and Enterococcus could not be found. It was effective in reducing bad E.Coli strains. There are no results for fibromyalgia, chronic fatigue syndrome or irritable bowel syndrome.

Bottom Line

There is nothing that explicit said that you should not use it. On the other side, there is nothing that clearly says that you should use it (unless you have candida). It does not appear to alter the microbiome in any significant method.

Bottom Line: No opinion.

 

 

AHCC and the microbiome 

A reader posted a comment on AHCC. He reported improvement from it and add it to his other rotating antimicrobials.

“Antimicrobials were wormwood, black walnut, olive leaf extract, curcumin, turmeric/piperine, monolaurin, thyme, oregano oil, Pau D’Arco, neem, caprylic acid, boswellia and now AHCC. Most I have done a couple of rotations. I may have forgotten one or two. In the early days I did one at a time, but later on did two at a time.”

Ken did a post a few months ago on amino acids. I have benefited from supplementing them as well.” – Reader

I was curious on what it is known about AHCC.

  • Active hexose correlated compound (AHCC) is a product prepared from the mycelium of edible Basidiomycete fungi that contains oligosaccharides…rats treated with AHCC had higher aerobic and lactic acid bacteria counts as well as higher bifidobacteria counts, whereas clostridia were reduced when compared with the TNBS group. ” [2007]
  • the oral treatment with AHCC protected mice from lethal infection with Pseudomonas aeruginosa and intraperitoneal one also protected mice from infection with methicillin-resistant Staphylococcus aureus (MRSA).” [2000]
  •  administration of AHCC… increased ability to clear bacteria. ” [2003]
  •  AHCC may display a protective role against opportunistic fungal infection” [2003]
  • suggest that AHCC protects mice in this model by restoring the immune and other systems negatively affected by trauma, infection, and food deprivation. ” [2006] – which may also include mal-absorption.
  • AHCC appears to induce an early activation of the immune response, leading to an effective clearance of bacteria and rapid recovery.” [2008]
  • Supplementation with AHCC appears to modulate immunity and increase survival in response to acute infection (including influenza virus, avian influenza virus, Klebsiella pneumoniae, Candida albicans, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus)  and warrants further investigation.” [2008]
  • Enhanced immune function observed with AHCC could be caused by attenuated concentrations of stress hormones and catecholamines.” [2013]


Bottom Line

AHCC looks very promising for CFS.  It shifts bacteria in the right direction and kills off and clears many pathogens. 

Cholesterol in CFS and Microbiome

Overall cholesterol has been reported normal with CFS, but HDL (the good cholesterol) is significantly low. This can result in MDs doing symptom/lab results treatment instead of addressing the root cause.

  • “Plasma lathosterol was decreased in both males and females with CFS (Tables 2 and and3).3). Total plasma cholesterol, desmosterol, cortisol, and aldosterone were normal in both males and females with CFS….Our data are consistent with increased flux through the desmosterol pathway to maintain normal cellular levels of cholesterol. The desmosterol pathway corresponds to the stress-inducible arm of de novo cholesterol and sterol synthesis.” [2016] While total cholesterol was normal, the mechanism of production was not.
    • “Plasma chenodeoxycholic acid (CDCA) was decreased in females (Table 3, Females). CDCA is a primary bile acid made from cholesterol. Decreased cholesterol flux can result in decreased substrate for bile acid synthesis needed for normal fat digestion and microbiome signaling (24). The absence of adequate bile acid delivery can lead to a loss in intestinal mucosal integrity and leaky gut via a cascade of events stemming in part from disrupted farnesoid X receptor signaling”
    • “These facts suggest that CFS is an evolutionarily conserved, genetically regulated, hypometabolic state similar to dauer that permits survival and persistence under conditions of environmental stress but at the cost of severely curtailed function and quality of life.” – except the stress in this case is caused by bacteria shifts.
  • “The CFS group had higher levels of triglycerides (p = 0.03), MDA (p = 0.03) and CO (p = 0.002) and lower levels of HDL cholesterol (the good cholesterol) (p = 0.001) than the control group. There were no significant differences in the levels of total protein, total cholesterol or LDL cholesterol...The CFS group had an unfavorable lipid profile and signs of oxidative stress induced damage to lipids and proteins. ” [2012]
  • “a control group of 40 healthy women and 40 CFS women. Levels of total cholesterol (TC), triglycerides (TG), LDL cholesterol (LDLc), HDL cholesterol (HDLc), and malondialdehyde (MDA) levels were measured. There was a negative correlation between HDLc and MDA levels (r=0.3; P=.046), a positive correlation between TG and MDA levels (r=0.4; P=.006), and lower levels of HDL cholesterol in the CFS group (P=.036). [2010]
  • “Bacteroidetes showed positive correlation with LDL- and HDL-cholesterol levels, whereas Firmicutes showed negative correlation with total cholesterol, LDL- and HDL– cholesterol.” [2016]

Concurrent Treatment

Or should I say, how to help correct the shift of bacteria and improve HDL cholesterol. There were sufficient human studies to just use those.

“Recent population-based association studies have shown that the gut microbiota composition can explain a substantial proportion of the inter-individual variation in blood triglycerides and HDL-cholesterol level and predict metabolic response to diet and drug.” [2016]

  • Almond Oil – “almond oil elevating the levels of so-called ‘good cholesterol’, high-density lipoproteins (HDL), whilst it reduces low-density lipoproteins (LDL).” [2010] I suspect eating almonds may be as good or better.
    • ” replaced half of their habitual fat (approximately 14% of approximately 29% energy) with either whole almonds (WA) or almond oil (AO) for 6-wk periods… whereas HDL cholesterol increased 6%.” [2002]
  • The use of probiotic L. fermentum ME-3 containing Reg’Activ Cholesterol supplement for 4 weeks has a positive influence on blood lipoprotein profiles and inflammatory cytokines: an open-label preliminary study[2016]. “HDL cholesterol level rose from 1.60 to 1.67 mml/l,”  i.e. 4%.
  • “a probiotic containing… L. Casei, B.Bifiudu and L. Fermentum .. significantly increased HDL-cholesterol levels (2.7 from 0.9 ) compared with the placebo after 12 weeks.”  [2016] – a 200% increase in HDL.
  • “Previous clinical studies have reported mixed results regarding the effect of probiotics on lipid metabolism…Subjects treated with probiotics demonstrated reduced total cholesterol and LDL cholesterol compared to control subjects by 7.8 mg/dL (95% CI: -10.4, -5.2) and 7.3 mg/dL (95% CI: -10.1, -4.4), respectively. There was no significant effect of probiotics on HDL cholesterol or triglycerides.” [2015] L. Fermentum appears not to be included in this review.

The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids [2015].

  • “we identified 34 bacterial taxa associated with body mass index and blood lipids; most are novel associations. Cross-validation analysis revealed that microbiota explain 4.5% of the variance in body mass index, 6% in triglycerides, and 4% in high-density lipoproteins, independent of age, sex, and genetic risk factors. A novel risk model, including the gut microbiome explained ≤ 25.9% of high-density lipoprotein (HDL) variance, significantly outperforming the risk model without microbiome. Strikingly, the microbiome had little effect on low-density lipoproteins or total cholesterol.”

hdl

AkkermansiaChristensenellaceae (phylum Firmicutes; N18) and the phylum Tenericutes and higher levels of HDL (P=0.0047 and P=0.0006, respectively) [RED in chart above]… genus Eggerthella (N3) with  decreased HDL (P=6.3×10−5), [BLUE in chart above]”

“We observed that the gut microbiome makes a significant contribution, beyond that of clinical risk factors and genetics, to the individual variance seen in BMI and to the blood levels of triglycerides and HDL,but that it has little effect on LDL or TC levels. ”

Bottom Line

While the bacteria cited above are not currently available as a probiotics, we do have L. Fermentum available as a probiotic that has significant effect after 4 weeks and major effect after 12 weeks. Adding almonds as a regular part of your diet would also help.

 

Rotation and Pulsing: Herbs, Probiotics, Antibiotics

In my last post, we found that probiotics may last for just hours or months – depending on the sourcing and type of bacteria. Probiotic behaviors vary greatly. Some produce natural antibiotics that will kill off other species. Others do not — just reduce inflammation etc. or grow more aggressively than bad bacteria. Some commercial probiotics are documented in FDA filing to be easily killed by almost all antibiotics, not to persist and not to produce toxins against other bacteria (good or bad).

We have limited knowledge of which ones produces natural antibiotics, so my rule of thumb is that probiotics should be viewed as producing antibiotics. You should rotate them regularly to prevent resistance to their natural antibiotics occurring. The same applies to herbs. Changing providers when you finish a herb is similarly desired.

The lack of (successful) studies on fixing dysfunctional microbiome

My model appears to be well supported by  Kyberkompact lab results, published papers over seventeen (17) years, etc.

  • ” In contrast, in the stool samples there was a higher relative abundance of Bacteroidetes and lower abundance of Firmicutes observed in ME/CFS patients compared to healthy controls.” [2015]
  • ” For the anaerobes, the mean percentage distribution of Bacteroides spp. for the control subjects and CFS patients was 92.8% and 91% respectively; Bifidobacterium spp, 7.1% and 2%; Lactobacillus spp., < 1% and 0%. The incidence of CFS patients with faecal E.coli greater than the percentage mean of control subjects was significantly different to that of the Bacteroides spp. (7 vs 21 respectively, p=0.0001) suggesting the possibility of an antimicrobial interaction among bacterial species.” [1998]

What is lacking are studies showing consistent successful treatment that persists.

  • “The high success rate and safety in the short term reported for recurrent Clostridium difficile infection has elevated Fecal microbiota transplantation (FMT) as an emerging treatment for a wide range of disorders, including Parkinson’s disease, fibromyalgia, chronic fatigue syndrome, myoclonus dystopia, multiple sclerosis, obesity, insulin resistance, metabolic syndrome, and autism.” [2016]
    • I have corresponded with several people that had them, went into remission for months and then relapses
  • “Case reports of FMT have also shown favorable outcomes in Parkinson’s disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis.” [2015]
  • “This raises the question of whether restoration of a healthy microbiome via probiotics or other ‘dysbiosis therapies’ would be an optimal alternative, or parallel treatment option, to antibiotics.” [2016]
  • “The use of specific probiotics in patients with IBD can be recommended only in special clinical situations. There is no evidence for efficacy of probiotics in CD. By contrast, studies in UC have shown a beneficial effect in selected patients.” [2016]

My approach

The use of antibiotics must be divided into two groups:

  • Acute infection treatment – typically resolved by a single course of antibiotics over 2 weeks with a focus on a single bacteria.
  • Latent/chronic/persistent/occult infections – which are complex to treat.

It is the latter that is needed for CFS, FM and many autoimmune diseases. We are not trying to eliminate one bacteria but reduce dozens of families while increasing dozens of families. When some of the counts for families are reduced to 1% of normal or even 1% of 1% (1/10000), getting those counts up is a challenge, a 400% increase of some counts do not even touch the dysfunction.

We do not know the complete complex interactions between strains, species and families of bacteria. We try to change one item and the side-effects may leave the patient worst.

How to proceed?

My approach comes from being placed successfully into remission three times using rotating antibiotics. The first time, before CFS was a clinical diagnosis (in 1972-3, Incline Village was in 1984) and the physician went with the diagnosis of antibiotic resistant walking pneumonia – rotating antibiotics when one course did not resolve it. The latter two times, modelling treatment on Dr. Cecile Jadin’s protocol for occult rickettesia infections (although my medical records for the last time read chronic lyme).

Bacteria mutate and become resistant. You may eliminate 99%, but if the environment supports growth, that 1% grows quickly and the volume returns. Our goal is to reduce parts of this consortium of evil bacteria until the good bacteria can muscle back in. Each herb, probiotic or antibiotic will only influence a few families of bacteria. You can knock those back and then reduce their friends, and then their friend’s friends.

There is a little literature on rotation:

Pulsing

Pulsing is much less studied. If you rotate, you are in one sense pulsing. Again, very little literature because for most infections – a single course of antibiotics is sufficient to knock out one bacteria.

“The issue of whether it is better to administer antibiotics as an intermittent bolus dose or a continuous intravenous infusion has been debated for several decades.” [1988]

  • My own experience has been modeled on Jadin’s protocols (See this summary)
  • “While this study does not demonstrate a superior response to dosing metronidazole in a pulsatile fashion against B. fragilis and B. thetaiotaomicron isolates, the effect is comparable to that of conventional dosing regimens. Perhaps this novel dosing strategy would prove advantageous against other pathogens.” [2004] – no worst than taking it constantly etc.
  • “In the current study, use of pulsatile dosing against S. pneumoniae with reduced susceptibility demonstrates superior reduction in bacterial concentration compared to that of more traditional two- or three-times-daily dosing. However, further research exploring the mechanism for pulsatile dosing and confirmation of these results are needed before applying this information clinically.” [2006]
  • “Overall bacterial density reduction was similar between the regimens for the susceptible isolate and greater with pulsatile regimens against the less susceptible strain.” [2004] – pulsing works better when the bacteria is more resistant.
  • A 2012 mathematical modeling study pulsing may be the preferred application of anti-pathogens: “We find that constant dosing is not the optimal method for disinfection. Rather, cycling between application and withdrawal of the antibiotic yields the fastest killing of the bacteria.

Bottom Line

I advocate rotation and/or pulsing. See earlier post from 2015. The key for knowledgable medical professional to grasp is that we are not dealing with a infection of a single bacteria (classic) but overgrowths of dozens, perhaps hundreds of bacteria families. We need to correct the shift… and that is far more complex.

How long should I take one thing?  IMHO: 2 weeks minimum (typical course of antibiotics duration), 4 weeks maximum.