What is Oxidative Stress? Let’s review the two sources of Oxidative Stress and determine which source is more important. General Oxidative Stress is thought to be the only source of Oxidative Stress. However, Blood can also generate Oxidative Stress, which is also known as BLOS. This post provides information about why BLOS is more important compared to General Oxidative Stress. EBooks (and Books) and BLOS Health Hack Kits may help you fight BLOS for better health.
General Oxidative Stress
The mechanistic model of General Oxidative Stress starts with an elevated rate of metabolism that results in mitochondrial dysfunction. In turn, this leads to an increased production of reactive oxygen species (ROS). Medical researchers observe General Oxidative Stress in tissue cultures, but it is difficult to observe in the human body. How many biopsies are needed to identify the tissues sources of General Oxidative Stress? Instead, medical researchers rely on diagnostic methods that evaluate ROS or oxidation end products in blood, urine, or breath.
General Oxidative Stress and ROS
ROS includes O2− (superoxide radical), OH (hydroxyl radical) and H2O2 (hydrogen peroxide). Most folks are familiar with the many uses of hydrogen peroxide for cleaning, disinfecting, and more. For your health, excessive production of ROS including hydrogen peroxide can be dangerous. The ROS molecules diffuse into the bloodstream and react with biomolecules throughout the body. The end products of these ROS reactions can be measured in blood, urine, and breath. The general consensus on the primary cause of General Oxidative Stress is the high caloric content of the Western Diet.
Excessive alcohol consumption is a special case of General Oxidative Stress. It causes short periods of ROS generation in the liver and other organs. Short periods of ROS generation is a primary characteristic of General Oxidative Stress. It is due to the reliance on excessive substrate availability necessary for the elevated rate of metabolism. A second source of Oxidative Stress is from blood cells, which received little attention from medical researchers or the general public.
Blood Oxidative Stress
White blood cells and platelets can generate high rates of ROS, which is alarming when the patient does not have an infection. In 2008, Walter Paulus’ research group reported on ROS+ blood cells in both healthy (non-hospitalized) and congestive heart failure (CHF) patients. Here is the link for the Abstract of the research article describing Blood Oxidative Stress or BLOS: https://www.ncbi.nlm.nih.gov/pubmed/18957960 This article provides interesting BLOS data and I will focus on the most important findings, which escaped the attention of the researchers. The research community missed it, but this is understandable when you consider that there are over 200,000 research articles about Oxidative Stress. The Paulus’ paper is the proverbial “needle in the haystack” for Oxidative Stress.
BLOS was reported in two different ways (Cytoplasmic vs. Mitochondrial) in two different blood samples (Arterial vs. Venous) from two different groups (“healthy” vs. CHF patients). The level of BLOS (or BLOS#) refers to the percent of ROS+ blood cells (i.e., generate high levels of ROS). The most accurate measurement of BLOS# is the Mitochondrial measurement for the Arterial sample. Consequently, the Venous samples will always be the same or slightly greater compared to the Arterial measurement. This is due to the ROS transfer from a source (ROS+ blood cells nearby or General Oxidative Stress).
Here is a table that brings together the most interesting data in the paper.
So, What is Oxidative Stress?
Let’s start with the easier set of data for the CHF patients. It is clear that the BLOS# for the Arterial and Venous samples are identical. I interpret this as little contribution from General Oxidative Stress (1.5% of the Total Oxidative Stress or 1/65). Otherwise, the BLOS# for the Venous sample would be much higher. The Venous sample could have false positives or blood cells with high levels of ROS transferred from true ROS+ cells. Granted, there are fewer ROS- blood cells available (36%) for ROS to enter. However, the high level of BLOS should also generate even more ROS available in the plasma to diffuse into the ROS- blood cells.
To be complete, small vessel disease (SVD) could also increase the BLOS# for the Venous sample. SVD would increase the time available within the capillary network for ROS to transfer from a ROS+ blood cell to a ROS- blood cells. This does not appear to be the case for the CHF patients. Now let’s review the data for the “healthy” people.
Non-Hospitalized Just Means Non-Hospitalized
The group of “healthy” people have a much lower BLOS# for both Arterial and Venous samples compared to the group of CHF patients. Now, non-hospitalized doesn’t mean healthy. Certainly, one can be unhealthy and non-hospitalized. There is a clear difference between the Venous and Arterial BLOS# averages. The final row in the table provides the difference between the two values. It suggests that 30% (5/17) of the Total Oxidative Stress may be due to General Oxidative Stress or SVD or a combination of the two. Here is my explanation for the higher estimate.
Not All BLOS is Equal
If you examine the BLOS# values for Cytoplasmic Oxidative Stress, there is a much greater difference in the healthy group. The simplest explanation is that the rate of ROS generation from the ROS+ blood cells is much greater in the healthy group versus the CHF patients. (There is a figure in the paper not shown here that provides this evidence) Perhaps, the healthy group are more (metabolically) active compared to the CHF patients? This means that General Oxidative Stress is probably much lower than 30%. The CHF group suggests 1.5%, which is closer to 5-10% of the Total Oxidative Stress.
General Oxidative Stress Is Not Important
Another possible factor could be that General Oxidative Stress may not be active at the time of sampling. This explanation also suggests that General Oxidative Stress is not as important compared to BLOS. BLOS is continuous, while General Oxidative Stress is temporal (i.e., few hours). Finally, more research and a robust diagnostic tool to measure BLOS are imperative.
Here is more details on the BLOS# calculation.
In Step 1, I used Figure 5 from the publication cited to estimate the number of ROS+ blood cells for each pair of samples collected from the six volunteers. For Volunteer A, I estimated the Venous Count (blue dashed line) at 275 and the Arterial Count (red dashed line) at 150. I recorded the pair of values for each Volunteer in my Excel workbook.
In Step 2, I used a conversion factor from the publication where BLOS# of 17 is equivalent to 126 ROS+ blood cells. I applied this conversion factor (count x conversion factor) to each count and computed a BLOS# for the Venous and Arterial counts for each Volunteer (lower table). The difference (Venous BLOS# – Arterial BLOS#) is the contribution of General Oxidative Stress to the volunteer’s Total Oxidative Stress. Keep in mind that Small Vessel Disease (SVD) could also play a role. SVD is probably doubtful for all of the non-hospitalized volunteers except one that reported Hypertension.
Which volunteer has Hypertension? We will never know, but my money is on Volunteer A (the highest Venous BLOS#).
Healthy vs. Non-Hospitalized
Remember that this data corresponds to the “Healthy” group, but the description of “non-hospitalized” is more accurate. From this group, we learn that the minimum BLOS# is 5.4% (Volunteer D), which may provide guidance on a BLOS# that actually corresponds to “healthy”. However, Volunteer D also has a GOS# (General Oxidative Stress #) of 8.8%. Is this person healthy?
Is there a Healthy Level of BLOS?
What else can we learn from this analysis? The range of BLOS# is 5.4%-20.2%, while the range for the GOS# is 0 (-2.0%) to 16.9%. A comparison of the Averages of the BLOS# and GOS# suggests that BLOS is the more important source of Oxidative Stress. It also appears that half of this group do not suffer from any significant General Oxidative Stress.
Comparison of Two Sources of Oxidative Stress
The following table provides a summary of the main characteristics of the two sources of Oxidative Stress. General Oxidative Stress is still undefined with respect to the primary cause, tissue location, and duration. It is doubtful that it will ever be defined. In contrast, Blood Oxidative Stress is defined (ROS+ blood cells) and appears to be the dominant source of Oxidative Stress. One theory proposes that diet is the origin of Blood Oxidative Stress. Certainly, BLOS# measurements during the course of dietary studies will test this hypothesis.
Take Home Message
The data reviewed in the Post suggests that BLOS is the primary source (90% or more) of Oxidative Stress and demands more research. With the lowest reported BLOS level of 10%, it is unclear whether this is a healthy value. So, the only way to study General Oxidative Stress is to have a method for managing BLOS. Two different sources of Oxidative Stress causes confusion in medical research regarding dietary advice, fitness tips, and pharmaceutical research. I will post more information on these topics in the near future.
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