Fermentation & (l-d-)lactate production.

A few research papers show evidence for elevated lactate in CFS[1-3]. Lactate arises from fermentation and can come from endogenus (internal) production or from gut bacteria, but to complicate things there are also two types of lactate: l-lactate and d-lactate. I have described both lactate sources below in some detail, with links into wiki for further info.

Endogenus lactic acid fermentation

Most energy in animals comes from the conversion of glucose, proteins and fats obtained from the diet to ATP via aerobic respiration. In the case of glucose, it is first sent through glycolysis and converted to pyruvate, which is then converted to the common intermediate acetyl-CoA and fed into krebs cycle, which provides power (electrons) for oxidative phosphorylation; the latter two processes of which occur in the mitochondria. But we also use fermentation for energy production, where lactate is constantly produced from and converted to pyruvate by the enzyme LDH. Normal lactate levels remain relatively low and consistent. This is except for when cellular energy demand depletes oxygen, limiting aerobic respirations output, and cells can for short periods rely more upon lactic acid fermentation to supply energy.

Essentially fermentation allows the anaerobic production of energy simply from glycolysis (outside of the mitochondria), without the need for krebs cycle and oxidative phosphorylation as used in respiration, but it is relatively inefficient and produces waste products, like lactic acid. In animals this lactate is then exported to the liver (the cori cycle) and converted to glucose by gluconeogenesis, which then feeds back into glycolysis. But with excessive reliance upon lactic acid fermentation for energy, for instance during intense periods of physical activity, there can be a temporary build up of lactic acid, since the body's ability to remove it is exceeded.

Bacterial lactic acid fermentation

Fermentation is often the primary pathway used for energy production in many anaerobic bacteria and yeasts in the gut. Different bacteria use different fermentation pathways to create a variety of waste products such as lactate, butyrate, acetate and ethanol (yeasts). These fermentation products are then absorbed through the intestine. 'Good' or 'bad' bacteria can partially be defined by how beneficial or toxic these substances are to us.

For lactic acid fermentation, first sugars such as glucose are converted to pyruvate via glycolysis, pyruvate is then reduced by the NADH formed from glycolysis, and lactate is formed. Every molecule of glucose (6 carbons) yields 2 of lactate (3 carbons).

There are a few forms of lactate: some bacteria produce l-lactate, some d-lactate and others a racemic dl-lactate. Humans create and can only efficiently metabolise l-lactate [4], so high levels of d-lactate can be harmful and induce d-lactic acidosis, which may induce neuro-cognitive symptoms[5]. D-lactate is produced by many streptococcus strains, but can also be produced by many lactobacillius (lactic acid bacteria) strains. The most common strains in supplements which produce d-lactate are lactobacillius acidophilus, plantarum and bulgarius[6]. A d-lactate free probiotic is available from custom probiotics; culturelle should also be d-lactate free. D-lactate can be tested for by Biolab (UK) and Metametrix (US).

Research
1. Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome.
2. Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome
3. http://www.biolab.co.uk/docs/dlactate.pdf
4. D-Lactate in Human and Ruminant Metabolism

5. D-lactic acidosis. review.
6. Laboratory Evaluations. Richard S Lord.
7. http://en.wikipedia.org/wiki/Microbial_metabolism
8. http://commons.wikimedia.org/wiki/Category:Carbohydrate_metabolism
9. http://en.wikipedia.org/wiki/Metabolic_acidosis