12/13/2025
Cholesterol is NOT the culprit behind CV disease. Even AI will eventually give that info if you ask it the right question 👇
CHOLESTEROL.... OH NO!
There is not a week that goes by that I do not have to address the concern of "High Cholesterol" in my office. This may be the one lab that freaks everyone out more than any other. If they were as concerned about their blood sugar and insulin levels, it would be more valuable. The reason for this is mainly because of the emphasis their medical provider places on cholesterol and the fearmongering that takes place (take this statin or risk imminent death).
Here is some light reading for you on this Saturday morning. 😉
I have researched this topic, and the findings remain unclear. There is a wealth of information available. Almost every medical article starts with the statement, "We know LDL cholesterol is bad, but." If you begin your hypothesis with this, then every conclusion you come to may be wrong. I decided to take it to AI, where all information can be consolidated in seconds.
I have come to appreciate that when working with AI, you have to get very specific in the questions and challenge it frequently.
When I started the query, the only answer I received was that LDL cholesterol and APO B are harmful and contribute to atherosclerosis (the standard statement communicated by researchers). Of course it does; that is what we are told, and that is what artificial intelligence will understand based on what it is taught or communicated to it.
As I challenged this theory, it provided numerous studies that suggest these beliefs. So, I questioned the quality of the studies and their limitations in reaching this conclusion. It then communicated the various limitations and nuances in the risk for cardiovascular disease (maybe it is not all about LDL cholesterol and APO B, after all). You can see my findings below.
We know that LDL and cholesterol accumulate in the artery wall and are found within atherosclerotic plaque. This is common knowledge. The question then is whether it is the arsonist or the firefighter. There is a theory that cholesterol is transported to an inflamed and damaged artery to help in the repair process and calm the inflammation. If this is the case, why are we blaming the LDL and cholesterol rather than focusing on the real root causes (e.g., insulin resistance, leaky gut, pro-inflammatory diet, toxin exposures, stress, etc.).
In conclusion, it is not known whether LDL cholesterol, LDL particles, or APO B are responsible for heart disease. We know there is an association between them, but there appears to be much more to this story than meets the eye. The quick rush to lowering cholesterol does not improve the risk in any significant way. The studies conducted have either been epidemiological (long-term government studies by the NIH and others) or studies examining cholesterol-lowering, which have been most frequently conducted by pharmaceutical companies themselves (conflict of interest?). 💩
We also know that heart disease rates were low in the early part of the last century but have increased significantly over the past 50 years. That does not implicate cholesterol but rather diet and lifestyle factors. Additionally, studies have shown increased longevity in individuals with the highest cholesterol levels. Perhaps we should reconsider our approach to accepting information, not simply because someone says so, but rather by attempting to identify the real problem and address it so that we can truly begin to reduce the risk of cardiovascular disease. 💓
If it is this difficult to find the answers and understanding of the information, why should we expect our physicians and other allied health professionals to know the answer when we are clearly told that LDL and ApoB are bad, deadly, evil? I mean, the pharmaceutical companies told us so. The flawed research by Dr. Ancel Keys in the 1950s said so. The vegan rabbits fed a high-cholesterol diet all died of heart disease, so it must be true. The American Heart Association says it is true—drink your Canola Juice. 😂
Here are my findings. Please feel free to share with anyone who might be interested.
Query 1 *****
Cardiovascular Risk Evaluation in the Context of Lipid Profile
For an individual displaying elevated LDL particles and Apo B, combined with favorable lipid markers, the cardiovascular risk assessment becomes nuanced.
Lipid Profile Analysis
Elevated LDL Particles: Indicates a higher overall particle number, which can correlate with increased cardiovascular risk.
High Apo B: Serves as a marker for the number of atherogenic particles. Elevated Apo B suggests potential risk.
Low Small LDL Particles: This is favorable. Smaller LDL particles are considered more atherogenic, so having low levels mitigates some risk.
Low VLDL Particles: Indicates a lower risk of triglyceride-related cardiovascular issues, which is beneficial.
Low Triglycerides: Suggests good metabolic health and is generally associated with lower cardiovascular risk.
Good HDL Cholesterol: High levels of HDL are protective and help reduce cardiovascular risk.
Normal LP-IR Score: A normal Lipoprotein Insulin Resistance (LP-IR) score indicates that lipid metabolism is functioning well and suggests a lower risk related to insulin resistance.
Normal HOMA-IR: Indicates good insulin sensitivity, further supporting overall metabolic health.
While elevated LDL particles and Apo B can indicate increased cardiovascular risk, the favorable aspects of the lipid profile—specifically low levels of small LDL and VLDL particles, low triglycerides, and high HDL cholesterol, along with normal LP-IR and HOMA-IR scores—suggest a more complex picture.
Query 2 *****
Limitations of Studies on LDL Cholesterol and Apo B as Cardiovascular Risk Markers
Numerous studies have explored the relationship between LDL cholesterol, Apo B, and cardiovascular disease (CVD), but several limitations exist that affect the overall conclusions.
Key Limitations:
Population Variability: Many studies are conducted on specific populations, which may not represent the general population's genetics, lifestyle, and health status. This can result in skewed data that isn't widely applicable.
Focus on Correlation: Many studies establish correlation rather than causation. Just because higher levels of LDL or Apo B are associated with increased risk does not definitively mean they cause cardiovascular disease.
Defining Risk Thresholds: An ongoing debate exists about what constitutes “elevated” levels of LDL and Apo B. Different studies employ varying cut-off values, which can impact the comparability of results.
Confounding Factors: Other risk factors, such as inflammation, diabetes, or lifestyle choices, may confound the relationship between LDL, Apo B, and cardiovascular risk. Studies may not adequately control for these factors, making it challenging to draw clear conclusions.
Methodological Differences: Variations in measurement techniques (e.g., different assays for Apo B or LDL particle size) can yield inconsistent results.
Chronic vs. Acute Conditions: Many studies do not differentiate between chronic risk assessments and acute cardiovascular events. An individual's lipid profile can fluctuate over time, which can impact risk assessment.
Underrepresentation of Atypical Cases: Individuals who do not fit typical profiles (e.g., those with normal LDL but still experiencing cardiovascular events) may be underrepresented in studies, limiting understanding of the full risk spectrum.
Conclusion:
While LDL cholesterol and Apo B remain critical markers in assessing cardiovascular risk, their limitations must be recognized. Understanding that many individuals with cardiovascular events present with normal levels underscores the complexity of heart disease and the need for a multifaceted approach in risk assessment and management.
Query 3 *****
Continued Reliance on Apo B and LDL Cholesterol as Cardiovascular Risk Markers:
Despite limitations in studies and evidence that not everyone with cardiovascular events has elevated Apo B or LDL cholesterol, these markers continue to be emphasized in cardiovascular risk assessments for several compelling reasons.
Epidemiological Associations: Large-scale epidemiological studies have consistently shown correlations between high levels of LDL cholesterol and Apo B with increased cardiovascular events. While these correlations do not imply causation, they provide a significant basis for risk assessment.
Historical Context: Historically, LDL cholesterol has been the focus of cardiovascular research, leading to a substantial body of literature supporting its role in atherogenesis. This historical perspective contributes to its continued mention in clinical guidelines.
Clinical Trials: Numerous clinical trials (such as those involving statins) have demonstrated that lowering LDL cholesterol can reduce cardiovascular events. This causal link between intervention and outcomes helps solidify the role of LDL in cardiovascular health.
Risk Stratification: Apo B is a powerful marker for counting atherogenic particles. The understanding that elevated Apo B levels often correlate with higher risks makes it a useful tool for identifying individuals at greater risk for cardiovascular events.
Guideline Recommendations: Major health organizations, based on a wide range of clinical evidence, incorporate LDL cholesterol and Apo B into risk assessment models. These guidelines influence clinical practice and educate patients and healthcare professionals.
Simplicity in Measurement: LDL cholesterol levels are relatively straightforward to measure and interpret, making them practical tools for healthcare providers. This ease of use keeps them in clinical conversations.
Incremental Knowledge: Research continues to explore the roles of these markers. While they may not tell the whole story, they are part of a growing understanding of cardiovascular health. They serve as useful indicators when combined with other factors like inflammation, lifestyle, and genetics.
Absence of Insulin Resistance:
Insulin sensitivity is a crucial factor in metabolic health. The absence of insulin resistance generally indicates better metabolic function and can reduce cardiovascular risk.
Normal CRP Levels:
A normal C-reactive protein (CRP) level indicates low systemic inflammation, which is protective and further mitigates cardiovascular risk. Elevated CRP levels are often associated with inflammation and increased heart disease risk.
No Metabolic Syndrome:
The absence of metabolic syndrome (characterized by abdominal obesity, high blood pressure, high glucose levels, and abnormal lipid profiles) significantly reduces cardiovascular risk. Metabolic syndrome has been shown to substantially increase the risk for heart disease.
Overall Risk Evaluation:
While high LDL cholesterol and Apo B levels can be indicators of increased cardiovascular risk, the overall risk may not be significantly elevated in the context of optimal metabolic health (normal insulin sensitivity, low CRP, and absence of metabolic syndrome).
The Bigger Picture:
Acknowledging the limitations of LDL cholesterol and Apo B doesn’t negate their relevance; it highlights the importance of a holistic approach. Cardiovascular disease is multifactorial, and these markers represent just one aspect of a complex interplay of factors.
Query 4 *****
Considering Apo B's Role: Protective Mechanism vs. Atherogenesis
The role of Apo B and lipoproteins in atherosclerosis can indeed be complex, leading to debates about whether these particles are ultimately protective or contributory. Here’s a deeper exploration of this perspective:
Cholesterol as a Vital Molecule:
Cholesterol plays crucial roles in various physiological functions, including cellular membrane integrity, hormone synthesis, and antioxidant properties. It is essential for cell membrane structure and regulates various cell signaling pathways.
Transport of Cholesterol:
LDL, which contains Apo B, transports cholesterol to tissues, including areas of injury or damage. Within this context, the transport of cholesterol can be considered a mechanism to support tissue repair and regeneration.
Response to Injury:
The presence of cholesterol and Apo B in atherosclerotic plaques may suggest a response to vascular injury. When endothelium is damaged, inflammation occurs, and lipoproteins can accumulate at the site, potentially serving to restore normal function.
Inflammatory Response:
In the early stages of atherosclerosis, the body may use lipoproteins as part of an inflammatory response to injury. This can lead to the hypothesis that Apo B-containing particles are part of a repair process rather than solely culprits in disease progression.
Atherogenesis vs. Protective Role
Dual Nature of LDL:
While LDL and Apo B are implicated in atherosclerosis, it is essential to recognize that they also play roles in nutrient delivery and repair. The context matters—elevated levels of these particles can have adverse effects, especially if they lead to inflammation, but they might also be involved in recovery processes during tissue repair.
Balance Between Repair and Damage:
The delicate balance between Apo B's role in transport, inflammation, and repair can be disrupted. When there’s an excess of Apo B-containing lipoproteins, it can lead to excessive inflammation and plaque formation, overshadowing their potential benefits.
Evolving Understanding:
Recent research is starting to acknowledge that while Apo B and LDL particles can contribute to pathology, their presence may also indicate an active biological response to vascular injury. An evolving understanding of this duality prompts further investigation into therapies that balance cholesterol management with tissue repair needs.
Conclusion:
Apo B's presence in atherosclerotic plaques indeed raises questions about its role as both a protective mechanism and a contributor to atherogenesis. While elevated levels are generally viewed as a risk factor for cardiovascular disease, they may also indicate a physiological response to vascular injury and damage.
