Lactic Acid in Health and Disease

 Introduction

Lactic acid is produced for energy when mitochondria can't use oxygen for aerobic respiration. 

Lactic acidosis develops when you have too much lactic acid in your body. Athletes monitor their blood lactate levels as a way to pace their training.  Chronic resting lactate levels greater than 2 mmol/L represent hyperlactatemia, whereas lactic acidosis is generally defined as a serum lactate concentration above 4 mmol/L.   High levels of lactic acid can cause muscle soreness, fibromyalgia-like symptoms, and anxiety.

Overproduction or Under-removal?

The body naturally produces and consumes lactate: although anaerobic exercise can raise blood lactate levels over 10 mmol/L, resting lactate in health adults is usually between 1 and 2 mmol/liter and is constantly produced and consumed.  High levels of lactic acid can be caused by overproduction or under-removal of lactate.

Resting lactate is usually between 0.5-1.5 in a large (10,000 participant) study of healthy adults.  More info.

Although many organs consume lactate, the liver and the kidney represent the major sites of lactate uptake and clearance as they metabolize approximately 53% and 30% of daily lactate production, respectively. Lactate is metabolized by two main mechanisms: First, lactate can be used as a substrate to regenerate glucose by gluconeogenesis, a process that is exclusive to liver and the kidney. Second, at least 50% of circulating lactate is removed and metabolized by means of oxidation during resting conditions. Unlike gluconeogenesis, which is restricted to liver and kidney, oxidation can take place in many organs, including the heart, brain, and skeletal muscle.

Supplements that affect Lactic Acid

Biotin (B7) is a cofactor required for gluconeogensis.  Aspirin can increase lactate levels by interfering with LDH lactate dehydrogenase, the enzyme responsible for turning lactate into pyruvate for gluconeogensis.   B1 deficiency impairs Citric Acid cycle and leads to accumulation of pyruvate and lactate.  Organic acids involved in the Citric Acid cycle may may provide substrates to better metabolize lactate and may reduce the acidifying side effects of elevated lactate (i.e. reduce Potential Renal Acid Load (NRAL)).  Nutrient deficiencies of CoQ10 and lipoic acid have also been associated with elevated lactic acid levels in both urine and blood.   Magnesium in muscles helps to decrease contractions and lactate buildup.  

Exercise

Slow exercise (i.e. HR below 100) can lower blood lactate and blood glucose levels in healthy adults.

Mitochondrial Dysfunction in Disease

Many diseases, included Type-2 diabetes, Chronic Fatigue Syndrome, and Long Covid, are associated with mitochondrial dysfunction and increased resting lactate levels.  Post-exertional malaise (PEM) is a major symptom of ME/CFS and Long Covid and may be caused by elevated lactate levels.  Although we don’t know the cure, #StopRestPace is the best treatment because only resting and then reducing/pacing activity can lower lactate levels.  

Lactic acid is being investigated as a possible metric of Long Covid and PEM severity.  If it plays a causal role in these diseases, methods that reduce lactic acid buildup may be promising treatments.  

Research

Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome. https://www.nature.com/articles/s41598-019-55473-4

-Patients having ≥1 lactate measurement ≥2 mmol/L defined elevated lactate group. The study included 123 patients. Elevated (n = 55; 44.7%) and normal (n = 68; 55.3%) lactate groups were comparable except for PEM, which was more severe in the elevated lactate group.

Decreased Fatty Acid Oxidation and Altered Lactate Production during Exercise in Patients with Post-acute COVID-19 Syndroms.  https://www.atsjournals.org/doi/full/10.1164/rccm.202108-1903LE

-The transition from fat oxidation to glucose oxidation occurs prematurely, suggesting metabolic reprogramming and dysfunctional mitochondria.

Figure 1 from paper.  Long Covid patients show greater increases in lactic acid at low intensity exercise compared to controls.  Blue and purple are Long Covid patients (with and without comorbidities (like diabetes), respectively) and grey and black are matched controls (with and without comorbidities, respectively).

How To Find The Truth (on the Internet)

I recently read about two different meta-review techniques: the Total Evidence Approach and the Quality Analysis Method, and that got me thinking about information processing and knowledge creation in our information-saturation internet-era.  How do we find the truth on the internet?

"In the total evidence approach (Kluge 2004; Sherman et al. 2008) all information is considered and data are not weighed by quality of evidence. Although the total evidence approach is subject to the biases and errors of individual studies, we deemed it preferable to the alternative “quality analysis” method (Sherman et al. 2008) in part because of the difficulty of objectively evaluating the relative validity and quality of the widely heterogeneous data sets that we reviewed."  Source.

I think we can all agree that a total evidence approach isn't going to work very well on the internet: there is simply way to much junk to try to average out truth from the hubbub.  But how to engage a quality analysis?  Michelle Nijhuis describes an iterative process of fact-checking in journalism, wherein she continually seeks out new sources to comment on and counterbalance other sources, until ideally, after an infinite(!) number of steps, truth is reached asymptotically.  But she admits this approach is time-intensive and unwieldy.  Furthermore, this approach can lead to the problem of "false objectivity":  journalists actively obscure truth when they try to objectively treat controversial issues by giving crackpots equal weight with experts and scientists. 

Instead,  I use a balance of evidence approach to truth-finding in science debates: I read widely and then select trustworthy sources.  If a person or organization publishes unsupported or erroneous information, I tend not to give them a second chance.  Also, sources that don't include open debates are outed as substandard information sources and discarded from the analysis.  A process of winnowing results, and after several months (years) of research, only the best sources are left standing.

Typically, the best sources are: experts who publish in-depth analyses of primary sources (e.g. journal articles).  They are open to quality comments from a range of voices, and their work is therefore continually self-correcting. 

Interestingly, I often prefer blogs over than traditional journals in my research.  Bloggers can attain higher standards of truth than the peer-review system.  Journals are slow to correct mistakes and often don't include enough discussion to reveal divergent viewpoints.  

Comparative Physiology: Maximum Lifespan

A conundrum if the amino acid methionine is a determinant of maximum lifespan: Why do carnivores and vegetarians live the same? Perhaps it could be for different reasons.... antinutrients for the latter and methionine for the former. These are universal rules that apply even between disparate physiologies. I haven't been able to find any papers that examine methionine diet content versus longevity.

Source: Ecology and mode-of-life explain lifespan variation in birds and mammals, Proceedings of the Royal Society B, DOI: 10.1098/rspb.2014.0298

This is a valuable resource on important "carninutrients" lacking in vegetarian diets.