Cort Johnson asks: Lactate – Is it Everywhere in Fibromyalgia and Chronic Fatigue Syndrome (ME/CFS)?, 1 March 2016

Lactate (L-lactate) is an organic compound produced during anaerobic energy metabolism.  It’s constantly being formed – even when we are at rest – but is formed in higher quantities when ATP levels are low and anaerobic energy metabolism is high. Several forms of lactate are also produced by anaerobic bacteria in the gut.

Do lactate levels suggest anaerobic issues are widespread in ME/CFS and/or FM

Lactate is not bad – it actually reduces muscle fatigue – but the presence of high levels of lactate (lactic acid) signal that the anaerobic energy production process – which produces toxic metabolites that cause pain and fatigue – is in full bore.

Lactic acidosis is a state of low pH accompanied by high lactate levels. It most commonly occurs in its temporary form after excessive exercise but is found in a more permanent form in people with illnesses which produce low oxygen levels (hypoxia/hypoperfusion) including heart or lung disease, sepsis, severe physical trauma, shock, Vit B deficiency, or interestingly enough, decreased blood volume.  Symptoms include a burning feeling in the muscles, muscle weakness, rapid breathing, nausea and vomiting.

The question this blog asks is whether the processes that produce lactate/lactic acid levels could be causing pain, fatigue, cognitive and other symptoms in fibromyalgia and/or chronic fatigue syndrome.

First a look at the gut.

The Gut

D-lactic acidosis is a different form of lactic acidosis caused by the production of D-lactate by bacteria in the gut. Two forms of lactate are produced in the gut. L-lactate in the gut is considered benign but the D-lactate hypothesis posits that D-lactate  contributes to leaky gut problems. It proposes that once D-lactate gets into the blood it can push its way through the blood-brain barrier into the brain where it can cause neurological symptoms including feelings of panic, hyperventilation, delirium, ataxia and slurred speech.

Sleep Sci. 2015 Nov;8(3):124-33. doi: 10.1016/j.slsci.2015.10.001. Epub 2015 Oct 23.Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study. Jackson ML1, Butt H2, Ball M1, Lewis DP3, Bruck D1.

Reducing the levels of streptococcus bacteria in some ME/CFS patients resulted in improved sleep and vigor.

This study reported on the effects of using an antibiotic to reduce Streptococcus bacteria levels in 21 ME/CFS patients. Prior tests indicated that these patients  – out of about 75 – had increased  Streptococcus and/or  Enterococcus bacteria.  Streptococcus spp. tend to produce lactic acid, including the D-lactic form which has been associated with increased gut permeability.

After the 21 ME/CFS patients were given an antibiotic, erythromycin,  to reduce the levels of lactic-acid producing bacteria in the gut, their sleep patterns were measured using an actigraph.  Fecal samples were taken after the antibiotic.

Of the 21 ME/CFS with increased bacterial levels, tests indicated significant declines in Streptococcus spp. in a third.  The patients with reduced Streptococcus spp. levels slept about 45 minutes longer each day and reported improved vigor. It was expected, given the results of other studies, that mood measures, in particular, anxiety might improve but that did not happen.

Antibiotic treatment alone was not sufficient to significantly alter the Streptococcus levels in the other ME/CFS patients, and increased sleep times or vigor were not seen in these patients.

Erythromycin – a broad spectrum antibiotic – also reduced Lactobacillus and Bifidobacterium levels in some patients – possibly putting their flora further out of balance.

The authors believed that the central finding of the study – that antibiotic treatments can reduce Streptococcus bacterial levels and improve sleep and vigor in some ME/CFS patients – supported the D-lactate hypothesis.  (They did not directly measure lactate levels in he blood or urine). Antibiotic treatment was not effective in lowering Streptococcus levels in most patients, however, and it may disrupt the flora of other bacterial species, including, presumably, some beneficial ones.

Several factors prevented the study from being definitive. It was small and because it was an open-label study, it was impossible to disentangle placebo effects from the effects of the antibiotic. Actigraphy is also unable to measure restorative vs non-restorative sleep.

(Antibiotics are not the only way to reduce levels of D-lactate producing bacteria in the gut.   Galland reports a case of a man with short bowel syndrome and D-lactic acidosis for whom antibiotics and dietary restrictions failed. The use of two probiotics, Bifidobacterium breve Yakult and Lactobacillus casei Shirota and the prebiotic galacto-oligosaccharide worked by limiting the growth of D-lactate producing bacteria.)

The Brain

In fact several studies do suggest lactate may be causing problems in chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM).  Sheedy’s 2009 study found that two species (E. faecalis and S. sanguinis) found in ME/CFS patients guts were high D-lactic acid producers.

Shungu believes the increased lactate levels he has twice found in the brains of ME/CFS patients may result from reduced oxygen levels. He believes increased oxidative stress may release substances called isoprostanes which restrict the blood vessels in the brain. Those constricted blood vessels result in low oxygen levels (hypoxia), anaerobic energy production and the release of lactate.

In a small study Baraniuk subsequently tied increased brain lactate levels in Gulf War Syndrome to reduced cognition.  A subset of GWS patients with increased brain lactate levels prior to exercise demonstrated significantly reduced cognition after exercise. Baraniuk attributed the cognitive decline to the brains inability to utilize the lactate produced by the muscles during exercise.  The inability to use the energy resource that lactate presented resulted in the brain using anaerobic metabolism to try and meet its needs.

Muscles: Fibromyalgia

Significantly higher elevations of lactate have been found in the trapezius muscle of fibromyalgia patients and in women with chronic widespread pain – a condition similar to FM.

While many lactate studies in FM have not been done some studies suggest that the conditions for increased lactate production such as low muscle oxygen levels (hypoxia) may be present.

Increased lactate levels have been found in the trapezius muscles of FM patients

Reduced oxygen intake during exercise was recently associated with increased pain in FM. Hypoxic conditions in the skin above tender points are present. Reduced capillary density, altered microcirculation and decreased muscle blood flows could help explain that finding.

Because muscle ischemia/hypoxia (low oxygen conditions) are associated with increased pain, it’s been suggested that they could be driving the central sensitization found in FM. (Staud points out that a more acidic mileu in the muscles – possibly produced by low oxygen conditions in FM – primes the pain receptors in the muscles to act up.)

EEG studies suggest the muscles in FM have trouble relaxing causing them to stay in a more contracted state – a state that can be associated with hypoxia and causes increased pain sensitivity. Another study suggested that deficient activation of the muscle units could be causing fatigue and leading to pain.

Mitochondrial problems are another possible cause of the increased lactate found in the muscles. Enlarged mitochondria, structural muscle abnormalities and reduced numbers of mitochondria all suggested “increased muscle stress” was present.  Biopsies of the trapezius muscle in FM have shown signs of mitochondrial disturbances.

Muscles: Chronic Fatigue Syndrome (ME/CFS)

A computer model of exercise intolerance caused by mitochondrial dysfunction in ME/CFS predicts increased lactate production in the muscles will occur.

Mitochondrial Depletion Could Underlie the Energy Problems in Chronic Fatigue Syndrome

Lane found increased muscle lactate production in ME/CFS three times. The third time he linked it to the presence of enteroviral RNA in the muscles.

Newton has shown that people with ME/CFS produce up to 20 times more acid and have more difficulty removing acids from their muscles during exercise. In a rather remarkable study Newton linked muscle pH issues in ME/CFS with hyperventilation and reduced oxygenation of the brain. Nijs’s finding that recovery of muscle function after exercise was associated with improved cognition suggested that muscle problems and brain functioning may be linked.

Numerous other studies, of course, have found problems with energy metabolism during exercise in chronic fatigue syndrome.

The Lactate Question

The lactate question ends up not being a question about lactate per se, but about whether widespread problems with anaerobic energy production are found in the brains, muscles and/or guts of FM and ME/CFS patients.  Multiple studies in both diseases suggest that that they may. High lactate or similar problems have been found in multiple areas ME/CFS and in the muscles of FM patients.

woman-tired-after-exerciseThe gut is the newest entry into the lactate question. Thus far the evidence that anaerobic bacteria are producing a form of lactate called D-lactate which causes cognitive, sleep, fatigue and other issues in ME/CFS is not particularly strong but it is tending in that direction.

Numerous studies on the other hand suggest that widespread low oxygen conditions could be causing a variety of problems including reduced energy production, muscle issues, increased pain and fatigue and cognitive problems in ME/CFS and FM.