Is Cholesterol a relevant biomarker for Cardiovascular diseases?

With adoption of western lifestyle & poor lifestyle choices, we have seen around 60% of the deaths are due to chronic inflammation/chronic diseases. Among various chronic diseases which have plagued our life, Cardiovascular disease is one of the most deadly & is the number one cause of death. In the US alone, every 40 seconds someone gets a heart attack or stroke. If we go by numbers, every year around 18 million people die of CVD worldwide.

Till now, we have been considering cholesterol to be the bad guy & the reason for heart attack & stroke. However, we have forgotten the basic functions of cholesterol AND Pharmaceutical industry has exploited this information asymmetry to make millions of dollars by propagating & endorsing a number of drugs, medications & antibiotics to lower the cholesterol level. Some of drugs we are consuming include( along with its impact on our health):

1) Diuretics which can cause mineral deficiencies, fatigue & high blood sugar levels.

2) Beta Blockers which can cause depression & asthma

3) Ace inhibitors can cause skin rashes & kidney damages 

In fact, these drugs can actually result in chronic illness including type 2 diabetes, liver damage & cardiovascular diseases. So have been doing all wrong & feeding our body with all chemicals & creating toxins detrimental to our overall holistic health?

Is cholesterol really a bad guy? You would be shocked to learn that CHOLESTEROL is essential for life. Some of the important things our body makes from cholesterol include:

1. Female Hormones- Estrogen, Progesterone
2. Make Hormones- Testosterone
3. Adrenal Hormone-Cortisol
4. Vitamin D
5. Cell membranes

AND MUCH MORE!

So if cholesterol is your friend, then what is killing so many people! LEAKY GUT & GUT DYSBIOSIS! Yes you heard it right- compromising your intestinal barrier & reduction of gut diversity is the major reason for causing heart diseases. Let us discuss this at length.

We have shared in our previous blogs that our body is host to trillions of micro-organisms living in our large intestine. As such there exists a symbiotic relationship between our gut bacteria & human body. The human body-gut bacteria interactions play a critical role in various metabolic & biological functions including regulating fat metabolism, nutrition & functioning of the immune system which directly impacts our body’s response to various pathological functions. Change in composition of gut microbiota results in decreased abundance of microbes & gut imbalance also referred to as gut dysbiosis which is a major reason for Cardiovascular Diseases. 

Atherosclerosis, one of the most common causes of cardiovascular diseases, occurs due to some of complex events happening in arterial walls involving lipid metabolism & inflammation. Accumulating evidence suggests that changes in gut bacterial composition has a role to play in cardiovascular diseases. Some of the gut microbes characteristics responsible for CVD include reduced abundance of gut microbes( having capacity of producing SCFA-Butyrate & increased circulating level of diet & microbiota dependent metabolites- TMAO-trimethylamine-N-oxide

Interaction between diet & gut microbiome can result in Atherosclerosis, Heart failure & Coronary Artery Disease. Western diet rich in red meat, poultry & high fat dairy products promotes bacterial metabolite TMA which is oxidised in the liver into TMAO which may contribute to Atherosclerosis. Reduced dietary fibre can lead to reduced Butyrate production which could lead to inflammation, gut dysbiosis & compromised intestinal gut barrier. This impaired gut barrier can lead to release of endotoxins such as lipopolysaccharides(LPS) further amplifying chronic inflammation.

One of the most prominent reasons for causing heart failure is altered gut microbiome with inflammatory properties & reduced capacity for production of short chain fatty acids such as Butyrate. In a recent study conducted, it was found that patients suffering from Coronary Heart Disease have reduced proportion of Bacteroidetes & increased proportion of Firmicutes. It was also found that such patients have increased abundance of Escherichia-Shigella and Enterococcus and lower abundance of the butyrate producers Faecalibacterium, Roseburia and Eubacterium rectale.Butyrate & various other SCFA(s) are released through fermentation of dietary fibres & are main source of energy for maintaining gut intestinal barrier. 

The gut dysbiosis impacting butyrate production also affects inflammatory pathways since Butyrate exerts anti-inflammatory effect on intestinal mucosa. Loss of Butyrate production bacteria can result in impaired gut mucosal barrier , resulting in leakage of endotoxin-LPS that binds to receptors of the immune system. This leads to chronic inflammation- the primary driving factor for CVD.Of interest, an increased potential for LPS biosynthesis in the microbiome has been reported among patients with CAD, and have linked circulating levels of LPS to insulin resistance glycemic control and abdominal obesity.  In a diseased state, the intestinal barrier loses its protective function leading to increased intestinal permeability, especially to  LPS by the gut bacteria. 

Nutritional Factors

High energy & excessive fat diet has been associated with high circulating levels of LPS in the blood. Two pathways have been involved in the increased LPS with such high energy/fat diets – direct and indirect. In the direct pathway, food high in fat content causes an increased accumulation of chylomicrons increasing the local intercellular pressure leading to loosening of the tight junctions. The loosening of tight junctions allows a generous influx of compounds & toxins such as LPS. In case of indirect pathways, the dietary fat/carbs stimulates mast cell activation in the intestinal mucosa with release of histamine and other inflammatory mediators said to increase intestinal permeability. Similarly  consumption of industrial food additives is said to impair intestinal barrier.

The most important reason for linkage between altered gut microbiome & TMAO is due to consumption of carnitine & choline, reflecting TMAO as an effective biomarker for occurrence of Cardiovascular diseases. More than just a biomarker, TMAO is a causative agent for Coronary Artery Disease(CAD). As mentioned above, the source of TMAO is TMA metabolite which is produced by gut microbiota from nutrients containing L-Carnitine (remember this is the most consumed body building & energy supplement for fat loss & muscle gain) & choline. Infact TMAO level increased in even healthy individuals after consuming red meat & high fat dairy products. This increase in TMAO level is more from Carnitine & less from choline.

Lifestyle Factors

Chronic stress & alcohol consumption can affect & alter our gut microbiome.Acetaldehyde, a product of alcohol metabolism, causes direct damage in addition to indirect damage by an increase in nitric oxide which damages microtubules. Alcohol consumption increases gram negative bacteria in the gut.corticotropin-releasing factor (CRF) that is responsible for stress responses can also play an important role in promoting leaky gut by communicating with gut bacteria & shutting down of the digestive system.

Now since we have found that it is our gut not cholesterol that causes CVD, our final section of the blog deals with the hack available to overcome & prevent such a dreaded disease.

1. Dietary Fibre/Prebiotic: Whole grain has been inversely associated with mortality from CVD. We can decrease the risk of CVD with adequate dietary fiber intake through the reduction of low-density lipoprotein. Prebiotics are fibers, that are selectively fermented (mostly Lactobacilli and Bifidobacteria genera) and exert changes on the composition and function of the gastrointestinal microflora.
2. Probiotics: Probiotics are live microorganisms that are said to improve our gut bacteria composition through Lactobacilli and Bifidobacteria rich foods.
3. Anthocyanin: These are a group of flavonoids commonly found in fruits, vegetables, grains, and red wine. They play a protective role against atherosclerosis. 

Learning your diet & consumption of animal protein & fat can help you optimize your gut bacteria & prevent/reverse occurrence of cardiovascular diseases. Want to learn how we are helping people understand their gut microbiome composition & keep them away from this dreaded disease ? Take our gut intelligence assessment test & fix up free discovery call to know more. 

Sources:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215967/#:~:text=Intestinal%20microbiota%2Dhost%20interactions%20play,including%20cardiovascular%20disease%20(CVD)

https://www.thelancet.com/action/showPdf?pii=S2352-3964%2820%2930024-4