Depression in CFS is different than conventional depression.

• “Abnormal cerebral perfusion patterns in CFS subjects who are not depressed are similar but not identical to those in patients withdepressive illness…Depressed patients differed from those with CFS in having relatively less perfusion of the left prefrontal cortex.” [2000]
• “Asymmetry (R > L) of tracer uptake at parietotemporal level is demonstrated in CFS as compared with Major Depression.” [1996]

In 1999, while reading up on antibiotic protocols for Chronic Fatigue Syndrome, I came across the reports of Dr. Philip Bottero, MD, who was doing a protocol of multiple rotating antibiotics very similar to Dr. Cecile Jadin, MD. The unusual thing was he was treating patients with psychopathies and obtaining a high rate of remission (Clinique de la Résidence du Parc, 1986) and “Chronic psychopathologies associated with persistent rickettsia and/or similar germs (chlamydiae)” Acta Mediterranea di Patologia Infettiva e Tropicale, 1987) – “For 60 cases of diseases that are called “Psychic” associated with persistent rickettsiae; we have: 55 good and excellent result, 5 failure,”

This caused me to suspect many psychological disturbances were the results of bacteria — more recently, gut bacteria. But what does PubMed says?

• “several medications (pioglitazone, metformin, exenatide, atorvastatin, gram-negative antibiotics), which have traditionally been used to treat metabolic disorders showed a certain potential to treat depression in first randomized controlled clinical trials.” [2015]
• “L. rhamnosus (JB-1) …these findings highlight the important role of bacteria in the bidirectional communication of the gut-brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress-related disorders such as anxiety and depression” [2011]
• “The concept that intestinal microbial composition not only affects the health of the gut, but also influences centrally-mediated systems involved in mood, is supported by a growing body of literature…. Bifidobacterium infantis…Probiotic treatment resulted in normalization of the immune response, , and restoration of basal NA concentrations in the brainstem.[2010]
• “B. infantis ….provides encouraging evidence in support of the proposition that this probiotic may possess antidepressant properties” [2008]
• “39 CFS patients were randomized to receive either 24 billion colony forming units of Lactobacillus casei strain Shirota (LcS) [Yakult] or a placebo daily for two months…. also a significant decrease in anxiety symptoms among those taking the probiotic [2009]
• “a multispecies probiotic containing Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, and Lactococcus lactis (W19 and W58)  …. provide the first evidence that the intake of probiotics may help reduce negative thoughts associated with sad mood.[2015] Note: This is a Ecologic probiotic and should be available in Europe (soon)!
• “we compared the effects of two different Bifidobacteria on anxiety and depression-like behavior; an antidepressant was also used as a comparator…  whereas B. longum 1714 induced antidepressant-like behavior in the tail suspension test.” [2014] [PDF-2015]
  • “these data suggest that B. longum 1714 had a positive impact on cognition and also that the effects of individual Bifidobacteria strains do not generalise across the species. ” [2015] i.e. not any B.Longum will have this effect.

In my last post I had discovered the migraine –> CFS pathway: Increased risk of chronic fatigue syndrome in patients with migraine: A retrospective cohort study [Oct 2015]. This suggests that migraines may be an indicator of the start of a dysfunction leading to CFS in some patients, see “evidence linking the migraine brain to various GI disorders” [What the Gut Can Teach Us About Migraine Jul 2015] and an even older study Migraine of gastrointestinal origin[1995].

In this post, I am going to attempt to drill into this because many CFSers suffers from migraines (just like they suffer from POTS and IBS very often).

• “Several studies demonstrated significant associations between migraine and celiac disease, inflammatory bowel disease, and IBS.” [2014]
• “probiotics [Ecologic(®)Barrier, 2.5×10(9) cfu/g] may decrease migraine supporting a possible role for the intestine in migraine management. Feasibility and lack of adverse reactions justify further placebo-controlled studies” [Oct 2015]

  • Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, L. casei W56, Lactobacillus salivarius W24, and Lactococcus lactis (W19 and W58).

• “a trend of more frequent H. pylori infections in patients with migraine” [2014]
• “it has been documented that at 6 and 12 months, bacterial eradication [of H. Pylori] is associated to disappearance of symptoms in 23% and 28% of cases, and to a significant decrease of intensity, frequency and duration of acute attacks in the remaining patients.”[2013] – note that the antibiotics used impacts many families of gut bacteria
  • The effect of Helicobacter pylori eradication on migraine: a randomized, double blind, controlled trial[2012].
  • Beneficial effects of Helicobacter pylori eradication on migraine[1998].
• “There is a growing body of literature on the potential use of .. diet interventions for primary headache disorders. This review identified literature on the use of a variety of diet and nutraceutical interventions for headache. Most of the studies assessed the efficacy of these interventions for migraine, though some explored their role in tension-type headache and cluster headache. The quality of the evidence in this area is generally poor.” [Jun 2015]
• “led to the identification of two potential compounds present in live green real veggies which could be considered for anti-migraine activity with better binding affinities than the reference drugs used and with liver-protective properties.” [2015]
  • “The product contains, among other constituents, glucosinolate (cabbage and broccoli), glutathione (cabbage, broccoli, parsley), sulforaphane (cabbage and broccoli), indole-3-carbinol (from cabbage), carnitine (carrots) and betaine (beetroot). The team points out that indole-3-carbinol and sulforaphane can cross the blood-brain barrier whereas other components cannot and many are not even absorbed by the body when taken by mouth.” [ScienceSpot] – Comment: these veggies are inline with the class of vegetables that I advocate are good for CFS.
• “A significant inverse relation was observed between dietary folate equivalent consumption and migraine frequency.” [Feb 2015] — reduces frequency but does not eliminate.

• “Migraineurs with aura were more likely to have low intake of chocolate, ice cream, hot dogs, and processed meats. Those who experience migraine at least once per week were more likely to have low intake of skim/low-fat milk and white and red wine.” [Aug 2015] –

• “effects of a low-fat plant-based diet intervention on migraine severity and frequency…A low-fat diet has been shown to reduce headache frequency, intensity, and duration, with subsequently lowered medication use..The most commonly reported triggers in these and other analyses include: chocolate, cheese, citrus, alcohol, and coffee’[2014]

• “our results support the idea that sterile inflammation plays a role in migraine pathogenesis. ” [2011]

• “We also recommend the use of the following supplements in the preventative treatment of migraines, in decreasing order of preference: magnesium, Petasites hybridus, feverfew, coenzyme Q10, riboflavin, and alpha lipoic acid.” [2009]

  • Note the overlap with recommended CFS supplements with Petasites hybridus ,butterbur , feverfew being new herbs to review in a future post.

Bottom Line

Hopefully someone will fund a study testing each of the probiotics in this post on Migraines. There is a single study so far using a mixture that included L.Casei. At the moment, there is no data on which probiotics would be effective. Similarly, there have been no studies on the use of H. Pylori antibiotics on migraines when there was not H. Pylori present — I expect similar remission and relief rates would occur (i.e. H Pylori is not the cause, but the antibiotics are the cure for some!  aka Wrong Model, Right Treatment!)

The probiotic that I reviewed in my last post, BIFIDO|MAXIMUS, while untested in clinical studies for migraines has the appropriate characteristics according to the model that I am using. Ecologic(®)Barrier is a dutch probiotic that may be challenging to get for many

This is a review of clinically interesting items — posts on politics, speculation are excluded.

• “Individuals within the more severe cluster [of POTS] had significantly more brain fog at the beginning and end of the survey when compared to cluster two[less severe].” An assessment of fatigue in patients with postural orthostatic tachycardia syndrome[Oct 2015].

• “There was little evidence of differences in outcomes between the randomised treatment groups at long-term follow-up.” Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial [Oct 2015].
  • i.e. CBT, SMC, GET,APT have short term effects (i.e. possibly Placebo effects) but are not effective long term
• “IL-1β was significantly reduced in severe compared with moderate CFS/ME patients. IL-6 was significantly decreased in moderate CFS/ME patients compared with healthy controls and severe CFS/ME patients…Serum IL-7 and IL-8 were significantly higher in the severe CFS/ME group compared with healthy controls and moderate CFS/ME patients. IFN-γ was significantly increased in severe CFS/ME patients compared with moderately affected patients.” Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients[Oct 2015] [Full Text]
• “Severe CFS/ME patients differed from controls and moderate CFS/ME patients over time and expressed significant alterations in iNKT cell phenotypes, CD8(+)T cell markers, NK cell receptors and γδT cells at 6 months.” [Sep 2015]

• Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts[Oct 2015].

• Increased risk of chronic fatigue syndrome in patients with migraine: A retrospective cohort study [Oct 2015].

  • This suggests that migraines may be an indicator of the start of a dysfunction leading to CFS in some patients, see “evidence linking the migraine brain to various GI disorders” [What the Gut Can Teach Us About Migraine Jul 2015]
• Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine [Oct 2016].
• • Getting CFS after a “flu-like” illness may actually have been the flu — with the CFS being the failure of the gut bacteria alterations caused by the flu returning to normal.
• “CFS patients with the 5-HTT SS or SLG genotype had worse 30 weeks outcome than CFS patients with the 5-HTT LALG, SLA or LALA genotype.” [Oct 2015]
• “The results suggest that patients with CFS/FM are more disabled, have more cognitive complaints, and improve more slowly over time than patients with CFS alone. Specific cognitive difficulties are related to worse functional status, which supports the addition of cognitive difficulties to the FM case criteria.” [Oct 2015]
• “Associations Between Cognitive Performance and Pain in Chronic Fatigue Syndrome: Comorbidity with Fibromyalgia Does Matter.[Sep 2015]”
• “Dysregulation of acetylcholine and adrenergic signalling could also explain various clinical symptoms of CFS.” [Sep 2015]
• “The results from this pilot study suggest that NK cells from CFS/ME and MS patients may have undergone increased differentiation in response to external stimuli which may affect different mechanisms in the NK cell cytotoxic activity pathway.’ [Sep 2015]

What was interesting..

• First item: migraine may be cause by a gut bacteria dysfunction and increases the odds of getting CFS.
• Second item: That flu was associated with CFS (but not the vaccine) which agrees with prediction from my model. The vaccine would produce much less gut bacteria alteration than having the flu.

A friend message me about salicylate sensitivity [SS] which he had in the passed assumed was part of his condition.  I had not heard that term for a while and it occurred to me that some salicylate sensitivity symptoms could actually be a shift of the microbiome. An interesting question which I hope to explore in this post.

• “Salicylates are derivatives of salicylic acid that occur naturally in plants and serve as a natural immune hormone and preservative, protecting the plants against diseases, insects, fungi, and harmful bacteria… There are no laboratory or skin testing methods for testing salicylate sensitivity.” [wikipedia]

Robert H. Loblay, The Role of Food Intolerance in Chronic Fatigue Syndrome, in Dr.Hydes “The Clinical and Scientific Basis of M.E. / CFS [1992]” raises the issue, and was likely the source of many CFSers opting on the SS cart. There have been no PubMed studies following this hypothesis up, in fact, a salicylate is often used for treating Irritable bowel syndrome which is co-morbid with CFS.

• “Mesalazine (5-aminosalicylic acid) alters faecal bacterial profiles, but not mucosal proteolytic activity in diarrhoea-predominant irritable bowel syndrome.‘ [2011]

This suggests that reaction to salicylates is more likely due to alteration of the microbiome profile (with possible die-off/herx of some bacteria) than true salicylate sensitivity.

• “Four OTUs (Prevotella spp., Bacteroides spp, family Ruminococaceae, Barnesiella spp.) discriminated aspirin users from no medication (AUC=0.96; 95% CI 0.84, 1.00).” [2015]

So are you or are you not? The easiest way to test is to look at two lists of high histamine foods and see if you do not react to any items on the high list. List 1 and List 2. Salicylate sensitivity and histamine sensitivity are both easy “answers” to latch on to — often without anything solid to confirm it. It is good to be scientific and verify against detail, actually measured lists to see if there is actual consistency. Often the popular list miss some high items, which you may be eating with no side effects — no side effects calls the presumption of salicylate sensitivity into question.