The study found that FM patients brain lactate levels were indeed elevated at rest – and not by a small amount (P<.0001). The FM patient’s brains were loaded with lactate, relative to the healthy controls.
High Lactate – Low Energy
High lactate levels are usually associated with reduced oxygen levels in the tissues.
When the cells don’t get enough oxygen to power the aerobic energy production process they turn to anaerobic energy production to produce energy.
This sounds like a mitochondrial issue. (see links at end of post)
During anaerobic energy production pyruvate is broken down into lactate, which then fuels the energy production process. This kind of energy production only works for short periods – two to three minutes in fit people – before fatigue and pain set in.
Lactate, therefore, is a natural outcome of anaerobic energy production. High blood lactate occurs when some lactate spills over into the blood.
High lactate levels are usually associated with strenuous exercise, however, not a “resting” brain.
Lower Lactate = Lower Pain
Savella lowered brain lactate levels significantly, and as it did so, it significantly reduced the FM patients pain.
The lactate levels in the FM patients brains were still significantly higher than in the healthy controls brains but probability factors indicated they were remarkably reduced (p <0001 vs p <.01).
As noted, Savella didn’t lower the FM brain lactate levels to normal. Nor did it leave the FM patients pain-free.
The significant reductions in both lactate and pain levels suggested, however, that further reductions in brain lactate levels could reduce pain levels further. It suggests that if researchers can figure out how to reduce brain lactate levels to normal the pain in FM might even disappear.
The reduced brain lactate did not significantly improve cognition, however.
The authors noted that these high lactate levels could function as a biomarker for both ME/CFS and FM. This is one potential biomarker, it should be noted, that does not require exertion to produce it; the high lactate levels are found during rest.
This could suggest that lactate accumulations in the brain – and the processes behind them – could constitute a fundamental part of ME/CFS and FM pathophysiology.
Intriguingly, the authors suggested that the increased lactate levels may result from neuroinflammation; i.e. by over-activated glial cells pumping out pro-inflammatory factors that are increasing oxidative stress and generally producing havoc.
The authors noted that activated glial cells have been tied to central sensitization
If increased brain lactate levels are linked to glial cell activation in FM and ME/CFS, then evidence of significant neuroinflammation has been present for chronic fatigue syndrome since 2009.
Savella – Antidepressant, Anti-Pain and Anti-inflammatory Agent?
But why would Savella – a serotonin and norepinephrine reuptake inhibitor – otherwise known as an antidepressant, be able to affect inflammation and glial functioning?
Research dating back at least to 2008 suggests, however, that antidepressants can also be potent anti-inflammatory agents.
A 2012 study, in fact, found that all the SSRI”s tested (fluoxetine, sertraline, paroxetine, fluvoxamine and citalopram) “potently” inhibited the microglia from pumping out pro-inflammatory factors (TNF-a, NO).
If it’s [Savella] helping with pain, this study suggests it’s probably reducing inflammation. (Since about a third of depression is associated with inflammation – the same may be true if it’s helping with depression.)
The Inflammation – Low Blood Flow Hypothesis
Earlier Shungu proposed that high levels of oxidative stress were producing elevated levels of free radicals called isoprostanes in the brains of ME/CFS patients.
This oxidative stress could result from glial cell activation, low antioxidant levels, or perhaps most likely – both.
Those isoprostanes then reduce blood flows and oxygen delivery to the brain by constricting the blood vessels in the brain.
The low oxygen levels then reduce aerobic energy production and increase anaerobic energy production -walla! – high lactate levels.
In this study Natelson and company provided evidence suggesting that
a) FM is a neuroinflammatory disorder,
b) Savella reduces pain levels by reducing inflammation in the brain and
c) that FM and ME/CFS share a central brain factor.
Below are links to other articles about the role of mitochondria in disease:
- The role of mitochondrial function in fatigue
- Mitochondrial Depletion Could Underlie the Energy Problems
- Is Fibromyalgia A Mitochondrial Disorder?
Here’s a list of links to previous posts on mitochondria: