What are normal cholesterol levels. How does cholesterol travel in the blood. Why is LDL considered the bad cholesterol. Who’s most at risk for having high cholesterol. Are there medicines that can help control the condition.

The Basics of Cholesterol: What You Need to Know

Cholesterol, a substance produced by the liver and released into the bloodstream, plays a crucial role in various bodily functions. Despite its negative reputation, cholesterol is essential for survival, contributing to skin maintenance and hormone development. However, when cholesterol levels become elevated, it can pose significant health risks.

Dr. Anil Purohit, a non-invasive cardiologist at HCA Healthcare’s Grand Strand Medical Center, estimates that between 100 to 102 million Americans are diagnosed with high cholesterol. Alarmingly, about 40 percent of the population remains underdiagnosed and undertreated with prescribed medications.

How Cholesterol Travels in the Blood

Cholesterol is transported through the bloodstream in particles called lipoproteins. These lipoproteins come in two main types:

• Low-density lipoproteins (LDL)
• High-density lipoproteins (HDL)

These lipoproteins carry cholesterol to different organs and areas of the body where it’s needed for various functions.

Understanding Cholesterol Levels: What’s Normal and What’s Not

Knowing your cholesterol levels is crucial for maintaining good health. But what exactly constitutes normal cholesterol levels?

• Total cholesterol:
  • Less than 170 mg/dL: Good
  • 170-199 mg/dL: Borderline
  • 200 mg/dL or higher: High
• HDL (High-density lipoprotein) cholesterol:
  • 45 mg/dL or higher: Good
  • 40-45 mg/dL: Borderline
  • Less than 40 mg/dL: Low
• LDL (Low-density lipoprotein) cholesterol:
  • Less than 110 mg/dL: Optimal
  • 110-129 mg/dL: Borderline
  • 130 mg/dL or higher: High

It’s important to note that these guidelines have evolved over time. Current medical practice often tailors cholesterol goals based on individual risk factors such as obesity, diabetes, high blood pressure, and age.

The Good, the Bad, and the Ugly: HDL vs. LDL Cholesterol

When it comes to cholesterol, not all types are created equal. Understanding the difference between HDL and LDL cholesterol is crucial for managing your health effectively.

HDL: The “Good” Cholesterol

High-density lipoprotein (HDL) cholesterol is often referred to as “good” cholesterol. It helps remove other forms of cholesterol from your bloodstream, transporting it back to the liver for disposal. Higher levels of HDL are generally associated with better heart health.

LDL: The “Bad” Cholesterol

Low-density lipoprotein (LDL) cholesterol, on the other hand, is known as “bad” cholesterol. The Centers for Disease Control and Prevention estimates that about 73 million American adults have high levels of LDL cholesterol. But why is it considered bad?

LDL cholesterol has a tendency to deposit in the lining of arteries, initiating a process called atherosclerosis. This buildup of plaque can occur anywhere in the body, potentially leading to serious health issues. When it develops in the heart, it’s known as coronary artery disease.

High Cholesterol and Heart Disease: Separating Fact from Fiction

A common misconception is that high cholesterol automatically leads to heart disease. While it’s true that elevated cholesterol levels significantly increase the risk of heart disease, it doesn’t guarantee its development.

High cholesterol is a major risk factor for heart disease, but it’s not the only one. Other factors, such as genetics, lifestyle choices, and other health conditions, also play crucial roles in determining an individual’s overall heart health.

Risk Factors for High Cholesterol: Who’s Most Vulnerable?

Understanding who’s most at risk for high cholesterol can help individuals take proactive steps towards better health. While some risk factors are beyond our control, others can be managed through lifestyle changes.

Genetic Predisposition

The most significant determinant of high cholesterol is genetics. Some individuals are genetically predisposed to produce more cholesterol or process it less efficiently, leading to higher levels in the blood.

Lifestyle Factors

Several lifestyle choices can contribute to elevated cholesterol levels:

• Sedentary lifestyle: Lack of regular physical activity can lower HDL cholesterol and contribute to weight gain, which can increase LDL cholesterol.
• Poor dietary choices: Consuming foods high in saturated and trans fats can raise LDL cholesterol levels.
• Tobacco use: Smoking damages blood vessel walls, making them more prone to accumulating fatty deposits. It also lowers HDL cholesterol.

Health Conditions

Certain health conditions can increase the risk of high cholesterol:

• Diabetes: This condition tends to lower HDL cholesterol and raise LDL cholesterol and triglycerides.
• Obesity: Excess weight can increase LDL cholesterol and lower HDL cholesterol.
• Hypothyroidism: An underactive thyroid gland can lead to increased LDL cholesterol levels.

Managing High Cholesterol: Treatment Options and Strategies

For those diagnosed with high cholesterol, there are several treatment options available. The choice of treatment depends on various factors, including the severity of the condition, overall health, and individual risk factors.

Lifestyle Modifications

The first line of defense against high cholesterol often involves lifestyle changes:

• Adopting a heart-healthy diet low in saturated and trans fats
• Increasing physical activity
• Maintaining a healthy weight
• Quitting smoking
• Limiting alcohol consumption

Medication Options

When lifestyle changes alone aren’t sufficient, medications may be prescribed. The most commonly prescribed medications for high cholesterol are statins. These drugs work by blocking a substance your body needs to make cholesterol, effectively lowering LDL cholesterol levels.

Different types of statins are available, varying in potency:

• High-intensity statins (e.g., Crestor, Lipitor): Can reduce cholesterol levels by up to 50%
• Moderate-intensity statins: Can lower bad cholesterol by 30-35%
• Low-intensity statins: Can decrease cholesterol levels by about 20%

The choice of statin and its dosage is typically based on individual patient profiles and the degree of cholesterol reduction needed.

How Quickly Do Cholesterol Medications Work?

The effectiveness of cholesterol medications can vary from person to person. Generally, you may see a change in your cholesterol levels within a few weeks of starting medication. However, it can take several months to achieve the full effect.

Regular blood tests are usually conducted to monitor cholesterol levels and adjust medication dosages as needed. It’s crucial to continue taking the medication as prescribed, even if you start feeling better or your cholesterol levels improve.

Beyond Medication: Holistic Approaches to Cholesterol Management

While medication can be highly effective in managing cholesterol levels, a holistic approach that combines pharmaceutical interventions with lifestyle modifications often yields the best results.

Dietary Strategies

A heart-healthy diet can significantly impact cholesterol levels. Consider incorporating these dietary strategies:

• Increase fiber intake: Soluble fiber can help lower LDL cholesterol. Good sources include oats, beans, lentils, and fruits.
• Choose healthy fats: Replace saturated fats with unsaturated fats found in olive oil, avocados, and nuts.
• Limit dietary cholesterol: While dietary cholesterol has less impact on blood cholesterol levels than previously thought, it’s still wise to limit intake, especially for those sensitive to dietary cholesterol.
• Incorporate plant sterols and stanols: These naturally occurring substances found in plants can help block cholesterol absorption.

Exercise and Physical Activity

Regular physical activity can help improve cholesterol levels by:

• Increasing HDL cholesterol
• Reducing LDL cholesterol
• Helping maintain a healthy weight

Aim for at least 150 minutes of moderate-intensity aerobic activity or 75 minutes of vigorous-intensity aerobic activity per week.

Stress Management

Chronic stress can negatively impact cholesterol levels. Incorporating stress-reduction techniques such as meditation, yoga, or deep breathing exercises can be beneficial for overall heart health.

The Future of Cholesterol Management: Emerging Treatments and Research

As our understanding of cholesterol and its impact on health continues to evolve, new treatments and management strategies are emerging. Here are some areas of ongoing research and development:

PCSK9 Inhibitors

These newer drugs work by blocking a protein that prevents the liver from removing LDL cholesterol from the blood. They can be used alongside statins for people with very high cholesterol levels or those who can’t tolerate statins.

Gene Therapy

Researchers are exploring ways to modify genes involved in cholesterol production and metabolism. This could potentially offer long-term solutions for managing cholesterol levels.

Personalized Medicine

Advances in genetic testing and biomarker analysis are paving the way for more personalized approaches to cholesterol management, tailoring treatments to individual genetic profiles and risk factors.

Nutraceuticals and Functional Foods

There’s growing interest in the potential of certain foods and natural compounds to help manage cholesterol levels. Examples include red yeast rice, berberine, and various plant-based compounds.

While these emerging treatments show promise, it’s important to note that they are still under investigation. Always consult with a healthcare provider before considering any new treatment options.

Taking Control of Your Cholesterol: Empowering Steps for Better Health

Managing cholesterol levels is a crucial aspect of maintaining overall health and reducing the risk of cardiovascular disease. Here are some empowering steps you can take to take control of your cholesterol:

Know Your Numbers

Regular cholesterol screenings are essential. The American Heart Association recommends adults aged 20 or older have their cholesterol checked every 4-6 years. If you have risk factors for heart disease, you may need more frequent testing.

Understand Your Risk

Work with your healthcare provider to assess your overall risk for heart disease. This assessment takes into account not just your cholesterol levels, but other factors like blood pressure, smoking status, and family history.

Set Realistic Goals

If you need to improve your cholesterol levels, set realistic, achievable goals. Remember, even small improvements can significantly impact your health.

Make Sustainable Lifestyle Changes

Rather than drastic, short-term changes, focus on making sustainable lifestyle modifications that you can maintain long-term. This might include gradually increasing your physical activity, slowly improving your diet, or finding stress-management techniques that work for you.

Be Medication Savvy

If you’re prescribed cholesterol-lowering medication, make sure you understand how to take it correctly. Don’t hesitate to ask your healthcare provider or pharmacist questions about potential side effects or interactions with other medications.

Stay Informed

Keep yourself updated on the latest research and recommendations regarding cholesterol management. However, always discuss any new information with your healthcare provider before making changes to your treatment plan.

Build a Support System

Managing cholesterol levels often involves lifestyle changes that can be challenging. Build a support system of family, friends, or support groups to help you stay motivated and accountable.

Remember, managing cholesterol is a journey, not a destination. It’s about making consistent, healthy choices over time. With the right knowledge, support, and commitment, you can take control of your cholesterol levels and improve your overall health.

Cholesterol numbers are in! Here’s what you should know.

U.S. President Donald Trump recently underwent his first physical exam since taking office and was declared in excellent overall health by the White House physician. Despite a clean bill of health, it also was noted that the President has a history of elevated cholesterol numbers, prompting HCA Healthcare Today to dig further into the common condition.

Anil Purohit, MD, a non-invasive cardiologist at HCA Healthcare’s Grand Strand Medical Center, sheds some light on what it means to have elevated cholesterol levels and the number of Americans affected.

“Many feel that the number of people affected by high cholesterol is underestimated. It’s anywhere between 100 to 102 million Americans who are diagnosed with this condition,” said Dr. Purohit, who focuses on preventative cardiology at Grand Strand Heart and Vascular Care. “Unfortunately about 40 percent of the population are underdiagnosed and undertreated with prescribed medications. ”

We asked Dr. Purohit a few more questions about cholesterol – the “good” and “bad” – and advice on ways to help reduce high levels below.

What is cholesterol?

It is a substance produced by the liver and released into the bloodstream. It is not all bad; it’s actually used for a wide variety of bodily functions. It’s responsible for maintaining the skin and developing hormones, for instance, so you need cholesterol in order to survive and for your body to keep building.

How does cholesterol travel in the blood?

It’s stored inside an envelope of lipids (fat) and is transported in particles called lipoproteins – low- density lipoproteins (LDL) and high-density lipoproteins (HDL). So, the cholesterol is transported through the blood to different organs and areas of the body that we need to build like skin and hormones.

What are normal cholesterol levels?

We say that a total cholesterol less than 170 is good. Anything between 170 and 199 is considered borderline and anything more than 200 is considered high. The total cholesterol is the HDL, LDL and a fraction of your triglycerides – another type of fat found in your blood.

Separately, a good HDL level should be as high as it can be – about 45 or greater; a low level would be anywhere less than 40 and borderline is between 40 and 45.

The LDL, which is considered the “bad” cholesterol, should be less than 110, however, that number varies depending on risk factors. If you have risk factors for heart disease, typically, we want to have that number less than 70.

Borderline LDL levels range between 110 and 129 and anything greater than 130 is considered high.

Those are the tried and true guidelines that we have been using. The guidelines have shifted over the years. Now, we target our cholesterol goals based on a patient’s risk factors: obesity, diabetes, high blood pressure, and age.

Why is LDL considered the “bad” cholesterol?

An estimated 73 million American adults have high levels of low-density lipoprotein, or “bad,” cholesterol, according to the Centers for Disease Control and Prevention. LDL deposits the cholesterol in the lining of the arteries, which are the blood vessels that connect different areas of the body. Our bodies are basically like a set of pipes that lead from one area to the other, all connecting through blood vessels. Due to the make-up of the LDL cholesterol, it has the propensity to develop build-up on the wall of the artery and starts a process called atherosclerosis, or plaque, most likely from cholesterol LDL deposits. The plaque can develop anywhere in the body. If it develops in the heart, it’s known as coronary artery disease.

Does having high cholesterol mean you’ll develop heart disease?

No, it doesn’t. Having high cholesterol certainly puts you at a much higher risk for heart disease, but it doesn’t necessarily mean that you’ll develop it, no.

Who’s most at risk for having high cholesterol?

The biggest determinant is your genetics. The others include:

• sedentary lifestyle;
• dietary choices – foods that have high saturated fat content are high in cholesterol;
• tobacco use/smoking – causes LDL to be released into the blood stream; and
• diabetes, which tends to cause fat distribution and LDL to increase.

Are there medicines that can help control the condition?

Yes, there are a class of medications called statins that are most commonly prescribed. We typically prescribe the class of statin based on each individual patient profile. There is the moderate to high intensity statin medications called Crestor or Lipitor. At the highest tolerable dose, they can reduce the cholesterol levels as much as 50 percent.  In moderate low doses, they can reduce bad cholesterol as much as 30-35 percent, while the lower potency doses can lower the cholesterol as much as 20 percent.

How long does it take for the prescribed medicines to work?

Many patients think their cholesterol results will automatically improve in a few months, but usually it takes anywhere between 6 months and 1 year to see some kind of effect. In my practice, if I haven’t seen anything in about 8 months, we may need to change the dose of your medications. So, it will take time; it’s not something that you’ll notice overnight.

What are other ways people can reduce their levels?

• Regular aerobic exercise, 30-45 minutes, four times a week, at least at a moderate pace,
• Eating more fruits and vegetables; it will increase your good cholesterol (HDL) while reducing your bad;
• Tobacco cessation, no smoking – we know that smoking causes the good HDL to decrease;
• Good healthy eating habits that include low saturated fats and;
• Managing some of the other co-existing risk factors that can sometimes drive high cholesterol like diabetes.

Dr. Anil Purohit is a board-certified cardiologist Grand Strand Medical Center and the practice of Grand Strand Heart & Vascular Care, affiliates of HCA Healthcare’s South Atlantic Division.

Triglycerides: Why do they matter?

Triglycerides: Why do they matter?

Triglycerides are an important measure of heart health. Here’s why triglycerides matter — and what to do if your triglycerides are too high.

By Mayo Clinic Staff

If you’ve been keeping an eye on your blood pressure and cholesterol levels, there’s something else you might need to monitor: your triglycerides.

Having a high level of triglycerides in your blood can increase your risk of heart disease. But the same lifestyle choices that promote overall health can help lower your triglycerides, too.

What are triglycerides?

Triglycerides are a type of fat (lipid) found in your blood.

When you eat, your body converts any calories it doesn’t need to use right away into triglycerides. The triglycerides are stored in your fat cells. Later, hormones release triglycerides for energy between meals.

If you regularly eat more calories than you burn, particularly from high-carbohydrate foods, you may have high triglycerides (hypertriglyceridemia).

What’s considered normal?

A simple blood test can reveal whether your triglycerides fall into a healthy range:

• Normal — Less than 150 milligrams per deciliter (mg/dL), or less than 1. 7 millimoles per liter (mmol/L)
• Borderline high — 150 to 199 mg/dL (1.8 to 2.2 mmol/L)
• High — 200 to 499 mg/dL (2.3 to 5.6 mmol/L)
• Very high — 500 mg/dL or above (5.7 mmol/L or above)

Your doctor will usually check for high triglycerides as part of a cholesterol test, which is sometimes called a lipid panel or lipid profile. You’ll have to fast before blood can be drawn for an accurate triglyceride measurement.

What’s the difference between triglycerides and cholesterol?

Triglycerides and cholesterol are different types of lipids that circulate in your blood:

• Triglycerides store unused calories and provide your body with energy.
• Cholesterol is used to build cells and certain hormones.

Why do high triglycerides matter?

High triglycerides may contribute to hardening of the arteries or thickening of the artery walls (arteriosclerosis) — which increases the risk of stroke, heart attack and heart disease. Extremely high triglycerides can also cause acute inflammation of the pancreas (pancreatitis).

High triglycerides are often a sign of other conditions that increase the risk of heart disease and stroke, including obesity and metabolic syndrome — a cluster of conditions that includes too much fat around the waist, high blood pressure, high triglycerides, high blood sugar and abnormal cholesterol levels.

High triglycerides can also be a sign of:

• Type 2 diabetes or prediabetes
• Metabolic syndrome — a condition when high blood pressure, obesity and high blood sugar occur together, increasing your risk of heart disease
• Low levels of thyroid hormones (hypothyroidism)
• Certain rare genetic conditions that affect how your body converts fat to energy

Sometimes high triglycerides are a side effect of taking certain medications, such as:

• Diuretics
• Estrogen and progestin
• Retinoids
• Steroids
• Beta blockers
• Some immunosuppressants
• Some HIV medications

What’s the best way to lower triglycerides?

Healthy lifestyle choices are key:

• Exercise regularly. Aim for at least 30 minutes of physical activity on most or all days of the week. Regular exercise can lower triglycerides and boost “good” cholesterol. Try to incorporate more physical activity into your daily tasks — for example, climb the stairs at work or take a walk during breaks.
• Avoid sugar and refined carbohydrates. Simple carbohydrates, such as sugar and foods made with white flour or fructose, can increase triglycerides.
• Lose weight. If you have mild to moderate hypertriglyceridemia, focus on cutting calories. Extra calories are converted to triglycerides and stored as fat. Reducing your calories will reduce triglycerides.
• Choose healthier fats. Trade saturated fat found in meats for healthier fat found in plants, such as olive and canola oils. Instead of red meat, try fish high in omega-3 fatty acids — such as mackerel or salmon. Avoid trans fats or foods with hydrogenated oils or fats.
• Limit how much alcohol you drink. Alcohol is high in calories and sugar and has a particularly potent effect on triglycerides. If you have severe hypertriglyceridemia, avoid drinking any alcohol.

What about medication?

If healthy lifestyle changes aren’t enough to control high triglycerides, your doctor might recommend:

• Statins. These cholesterol-lowering medications may be recommended if you also have poor cholesterol numbers or a history of blocked arteries or diabetes. Examples of statins include atorvastatin calcium (Lipitor) and rosuvastatin calcium (Crestor).
• Fibrates. Fibrate medications, such as fenofibrate (TriCor, Fenoglide, others) and gemfibrozil (Lopid), can lower your triglyceride levels. Fibrates aren’t used if you have severe kidney or liver disease.
• Fish oil. Also known as omega-3 fatty acids, fish oil can help lower your triglycerides. Prescription fish oil preparations, such as Lovaza, contain more-active fatty acids than many nonprescription supplements. Fish oil taken at high levels can interfere with blood clotting, so talk to your doctor before taking any supplements.
• Niacin. Niacin, sometimes called nicotinic acid, can lower your triglycerides and low-density lipoprotein (LDL) cholesterol — the “bad” cholesterol. Talk to your doctor before taking over-the-counter niacin because it can interact with other medications and cause significant side effects.

If your doctor prescribes medication to lower your triglycerides, take the medication as prescribed. And remember the significance of the healthy lifestyle changes you’ve made. Medications can help — but lifestyle matters, too.

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Show references

1. High blood triglycerides. National Heart, Lung, and Blood Institute. https://www.nhlbi.nih.gov/health-topics/high-blood-triglycerides. Accessed Aug. 7, 2018.
2. Bonow RO, et al., eds. Risk markers and the primary prevention of cardiovascular disease. In: Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 11th ed. Philadelphia, Pa.: Saunders Elsevier; 2019. https://www.clinicalkey.com. Accessed May 30, 2018.
3. Kumar P, et al., eds. Lipid and metabolic disorders. In: Kumar and Clark’s Clinical Medicine. 9th ed. Philadelphia, Pa.: Elsevier; 2017. https://clinicalkey.com. Accessed May 22, 2018.
4. AskMayoExpert. Triglycerides (adults). Rochester, Minn.: Mayo Foundation for Medical Education and Research; 2018.
5. AskMayoExpert. Hyperlipidemia (adult). Rochester, Minn.: Mayo Foundation for Medical Education and Research; 2018.

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Nutrients | Free Full-Text | Inflammation, not Cholesterol, Is a Cause of Chronic Disease

3.2. The PAF Pathway and Metabolism in Chronic Diseases

Under normal conditions, plasma and tissue levels of PAF are tightly regulated by its metabolic pathways. However, production of PAF and PAF-like molecules can become elevated and/or dysregulated during extended periods of immune activation and chronic inflammation-related disorders by amplification of its synthesis, either through cascades activating its biosynthetic enzymes or through oxidative production of PAF, or usually by both [57,69,70,79,81,103,104,113]. PAF plays a major role in the physiopathology of inflammatory reactions and is produced and released in large quantities by inflammatory cells in response to specific stimuli, such as upstream regulators (IL-1, IL-6, TNF-α, Endothelin, oxidative stress, and PAF itself; Figure 2A) [57,78,89,114].Increased PAF levels at the site of inflammation can activate several cell types through its receptor. This leads to the initiation of a broad spectrum of PAF effects depending on the cell type and tissue, which is achieved through the production and release of various downstream mediators, such as PAF itself and several other mediators of inflammation such as eicosanoids, cytokines (i.e., TNF-α, IL-1α, IL-6, IL-8, INF-γ, etc.), growth factors (i.e., VEGF, IGF, TGF), ROS, and RNS, but also through the expression of selectins and integrins (i.e., ICAM, VCAM, P-Selectin, E-Selectin) in the membranes of activated cells (Figure 2B) [57,58,78,89,113,114].The interconnected crosstalk between PAF, pro-inflammatory upstream mediators that induce PAF production, and PAF-induced downstream mediators seems to be interrelated during inflammatory manifestations and inflammation-related chronic diseases. These pathways serve as one of the main junctions between many inflammatory cascades that ultimately lead to endothelium dysfunction and inflammation-related disorders such as atherosclerosis, CVD, renal disorders, cerebrovascular, central nervous system (CNS) disorders, metastatic angiogenesis during cancer, sepsis, and several other chronic disorders (Figure 2B) [57,58,78,89,113].

3.2.1. PAF in Atherosclerosis and CVD

Cardiovascular diseases (CVD) are the leading cause of death worldwide. It is estimated that 49 million people are now living with the disease in the European Union alone [115]. Atherosclerosis is a slow progressive disease in which lesions or plaques form in large and medium-sized arteries, consisting of necrotic cores, calcified regions, accumulated modified lipids, migrated smooth muscle cells (SMC), foam cells, endothelial cells, and several leukocyte subtypes. Monocytes, circulating blood precursors of tissue macrophages, and myeloid-derived DC influence plaque development following recruitment into the intima and differentiation to foam cells. In contrast to the previous notions concerning the passive accumulation of lipids in macrophages during the formation of foam cells, it is now clear that there are more complex inflammatory mechanisms acting on monocytes, macrophages, platelets, several other leucocyte subtypes, and endothelial cells that seem to promote atherosclerosis via pro-inflammatory foam cell formation [66]. Persistent and unresolved inflammation at the vascular wall gives rise to inappropriate platelet and leukocyte recruitment at the endothelium. The inflammatory interplay and crosstalk between these cells and endothelial cells, facilitated by several inflammatory mediators, initiates the cascades that induce chronic inflammatory manifestations at the vascular wall, which counteracts the homeostatic inflammatory response, leading to endothelial dysfunction and initiation of proatherogenic events that lead to atherogenesis and atherosclerosis [116]. PAF is one of the main junctions between several inflammatory pathways (cytokines, oxidative stress, eicosanoids, etc. ) and their interplay with cells participating in inflammation-related atherosclerosis. Therefore, PAF is implicated in all stages of atherosclerosis, from the initiation of atherogenesis all the way through to plaque formation, development, instability, and rupture [58,89,105,117].

The Pro-Inflammatory Crosstalk between PAF with Several Cells and the Endothelium Induces Early Pro-Atherogenic Phases of Endothelial Dysfunction

At early pro-atherogenic conditions, PAF is produced in several cells, such as platelets, leukocytes, and endothelial cells under pro-inflammatory stimuli and/or by the oxidation of lipoproteins. Thus, PAF can further propagate oxidative stress, through the oxidation of LDL and the reduction of NO bioavailability, but mostly by acting as a potent chemotactic factor for other human cells that exhibit its receptor on their membranes, such as monocytic and granulocytic leukocytes of the innate and adaptive immune system, endothelial cells, etc. Following these activations, a number of mediators are released by these activated cells (e.g., PAF itself, several cytokines, eicosanoids, ROS, RNS, and several enzymes), while adhesive molecules are expressed in their cell membranes (i.e., chemokines, selectins, and integrins, such as E-selectin, P-selectin, MCP1, ICAM-1, VCAM-1, etc.) that facilitate platelet-platelet, platelet-leukocyte, and platelet-leukocyte-endothelium aggregates and interplay [58,89]. The PAF pathway downstream products can further contribute to the propagation of atherosclerosis.Molecules of the selectin family mediate interactions between platelets and leukocytes, with the endothelium allowing leukocytes and platelets to roll along the vascular endothelium wall. Platelet binding of the endothelium seems to precede the appearance of leukocytes in plaques and induces bidirectional expression of adhesion molecules and the production of monocyte attracting chemokines, such as PAF that plays a central role in cytokine-induced monocyte adherence to endothelium [58,89,117,118]. Activated platelets that adhere to the inflamed endothelium may enhance leukocyte recruitment, activation, and transmigration, thereby enhancing the inflammatory processes underlying atherosclerosis [119]. PAF and Leukotriene B4 (LTB4), derived by activated platelets, leukocytes or endothelium, but also thrombin (through PAF and LTB4 pathways), can propagate the activation of platelets and the subsequent activation and adhesion of leucocytes through the interplay of chemokines and their receptors [117]. An important aspect of this platelet-leucocyte interplay is the diversity of leukocytes recruited by vessel wall adherent platelets, such as the platelet-mediated recruitment of neutrophils, monocytes, DC, T-lymphocytes, B-lymphocytes, and NK-cells to endothelium [117].In addition, platelets regulate neutrophil activation through the generation of PAF as a chemoattractant pro-inflammatory lipid [120]. Activated endothelial cells and platelets generate considerable amounts of PAF, which act cooperatively with other extracellular stimuli to induce full integrin activation and leukocyte arrest [58,89,120]. However, whether PAF mostly originates from activated platelets, endothelial cells or leukocytes are not well defined yet [120]. Independently of its origin, the presence of PAF activates through its PAF/PAF-R pathways expression of integrin molecules at cell membranes to promote firm adhesion between leukocytes, platelets, and vascular endothelium [117].PAF, other vasoactive compounds, angiogenic compounds, and pro-inflammatory mediators, such as arachidonic acid metabolites, histamine, cytokines, chemokines, and proteolytic enzymes, can also be released by mast cells that accumulate in the human arterial intima and adventitia during atherosclerotic plaque progression, and thus aggravate atherogenesis [8]. Cytokines produced by mast cells may be activated by pro-inflammatory stimuli, including cytokines, hypercholesterolemia, and hyperglycaemia, and trigger the endothelial expression of adhesion molecules such as P-selectin, VCAM-1, and chemokines such as PAF that mediate the recruitment and adhesion of leukocytes [8].Similar to other chemoattractants, PAF has been detected in circulation; however, this molecule is mostly cell membrane-associated and operates in a paracrine manner on the G-protein coupled receptors of neighbouring cells [58,89,120]. Thus, PAF is also a main player in juxtacrine signalling and adhesion of leukocytes to other cells, and has also been shown to regulate firm neutrophil adhesion on the surface of immobilised spread platelets [119,121]. The level of platelet stimulation impacts directly on neutrophil adhesion to platelets monolayer, upon which neutrophil activity is spatially regulated by PAF generation [58,89,120]. Platelets and activated neutrophils act jointly to induce expression of adhesion molecules, permeability changes, and limit the bioavailability of nitric oxide, altogether aggravating endothelial dysfunction and facilitating subsequent monocyte plaque recruitment [122].

The Inflammatory Crosstalk Between PAF and Several Cells at the Intima and Subintima Leads to the Induction of Plaque Development and Increased Plaque Growth and Expansion

In the aortic lumen, endothelial cells have been activated by the aforementioned PAF-implicated downstream manifestations, leading to increased endothelium permeability and endothelial dysfunction. Subsequent abnormal recruitment, migration, and infiltration of monocytes then take place in the intima and subintima. Within the intima, monocytes secrete lipoprotein-binding proteoglycans, resulting in increased accumulation of modified LDL, which sustains inflammation. In addition, once in the intima, differentiation factors such as the macrophage colony-stimulating factor (M-CSF) differentiate pro-inflammatory monocytes into inflammatory type macrophages that ingest modified lipoprotein to become foam cells [59,123].Emerging evidence suggests that the role of monocytes and macrophages in atherosclerosis is not simply that of a passive acceptor of lipids [66]. Apart from their phagocytic roles, macrophages can also instruct or be instructed by other immune cells by producing various immune effector molecules and by acting as antigen-presenting cells (APC). Plaque-related macrophages can have many phenotypes and functions depending on the stage of the disease; several monocyte subtypes exist, and subsequently several pro-inflammatory and anti-inflammatory macrophage subtypes also exist, while macrophages can rapidly adapt their phenotype and consequently their function in response to changes of the microenvironment and intracellular signalling pathways [122]. After appropriate activation, macrophages can exhibit a pro-inflammatory phenotype that can further activate endothelial cells, which in turn triggers further blood monocyte recruitment [122,124]. Thus, upon activation, the pro-inflammatory subtype of macrophages and foam cells produce inflammatory cytokines and chemokines that enhance inflammation and further regulate monocyte and T cell infiltration [59,124].Macrophages express a myriad of receptors including G-protein coupled receptors such as PAF-R, through which they scan their environment for activation or polarisation signals, e.g., cytokines, growth factors, oxidised phospholipids, etc., [59,124,125,126], while, when in the atherosclerotic plaque, macrophages are capable of releasing a large repertoire of pro-inflammatory cytokines according to their phenotype and depending on the plaque microenvironment, including IL-1, IL-6, IL-12, IL-15, IL-18, TNF family members, and PAF, as well as anti-inflammatory cytokines like IL-10 and TGF-β family members (TGF-β1, BMPs, GDFs) [58,59,124].Several autacoid molecules of the microenvironment, such as PAF and its receptor, play a significant role in the pro-inflammatory activation of macrophages by oxidative stress and in the uptake of Ox-LDL by macrophages [125], since Ox-LDL contains inflammatory PAF-like oxidised phospholipids that mimic PAF and interact with these cells [105]. In addition, autacoids such as PAF and PAF-like molecules in Ox-LDL also play a significant role in the cytoskeletal reorganisation of these cells during differentiations [127], as macrophages engulf and retain large molecules such as Ox-LDL, oxidised phospholipids, and blood cells, which have also migrated into the intima and sub-intima. The macrophages become lipid-loaded foam cells through phagocytosis, scavenger-receptor mediated uptake, and pinocytosis; the macrophages become lipid-loaded foam cells [58]. The term ‘foam cells’ both reflects the microscopic appearance of these lipid-laden macrophages and denotes early fatty streak lesions [122]. This process is outlined in Figure 4.The interplay of PAF with other APC such as DC is also implicated in several stages of atherosclerosis. Under atherosclerotic conditions, the role of DC is to take up atherosclerosis-specific antigens, which become locally activated, and migrate out of the plaque towards either local draining or distant lymph nodes, where they induce protective anti-inflammatory T cell activation and proliferation. However, apart from their role in directing different T and B cell subsets, not all their functions have been fully elucidated or understood. Nevertheless, impaired migration of DC to lymph nodes results from inhibitory signals generated by PAF or Ox-LDL that act as a PAF mimetic, thus suppressing immunologic priming. In contrast, normal DC migration and priming can be restored by HDL or HDL-associated PAF acetylhydrolase (PAF-AH), which mediates inactivation of PAF and oxidised LDL. In this context, HDL and PAF-AH maintain a normally functional DC compartment [128]. In addition, DC produce PAF that engage the PAF-R in DC membranes during maturation, and thus the capacity of DC to present antigens to lymphocytes is downregulated, due to the induction of IL-10 and the sustained and increased PGE₂ synthesis mediated by the PAF-R. In contrast, PAF-R antagonists, by disrupting this suppressor pathway, increase DC function and could therefore be useful in increasing efficiency of vaccines and/or treatment [129]. The above PAF effects on DC perpetuate local inflammation, decrease the activation of anti-inflammatory T-lymphocytes, and thus further increase plaque growth.Lymphocytes, particularly T-lymphocytes, are also recruited to the vessel wall by mechanisms such as monocyte recruitment; thus, they are present in atherosclerotic lesions in parallel with macrophages, but in lower amounts. CD4+ T cells (also called Th2 cells) express pro-atherogenic roles, whereas prominent Th3 (CD8+ T cells) and Treg responses seem to exhibit unclear and still controversial anti-inflammatory effects, resulting in a reduction of atherosclerosis and/or a more favourable plaque morphology in atherogenesis. PAF and other platelet-related inflammatory mediators, such as thromboxane A₂, serotonin, and histamine, also display Th2 cell-regulatory effects towards the Th2 response that promotes the progression of atherosclerosis and diverse effects on Th3 response [130]. Activated platelets produce a significant amount of TxA₂, which inhibits Th2 proliferation and cytokine production [131], while they also express PAF-R, and PAF can enhance Th2 cytokine production [130,132].PAF can also promote differentiation of Th27 cells that are present in atherosclerotic lesions, which can induce cytokine production by these cells. Activated platelets and platelet thrombi create a unique microenvironment with counteracting mediators for Th27 polarisation by secreting substantial amount of PAF, TGFβ, and IL-1β [130]. However, the role of Th27 also remains controversial, as both atherogenic, as well as atheroprotective, effects have been reported [59]. Nevertheless, both PAF and Ox-LDL that mimic PAF and the PAF-R have the capacity to induce atherogenesis due to activation of T-cells and monocytes/macrophages [133]. These events lead to an expansion of atherosclerotic plaque burden and perpetuation of the pathogenic T-cell response.Overall, there is intricate interplay and crosstalk between a panel of inflammatory cells of both the innate and adaptive immune system. When key-junction inflammatory mediators within the developing plaque microenvironment are increased, there is favour towards inflammatory phenotypes in these cells, which perpetuates a continuous inflammatory milieu, leading to further increase and expansion of the atherosclerotic plaque. Subsequently, the intimal thickness increases, and blood flow is eventually impaired. Gradually accumulating foam cells die in the intima through inflammation induced apoptosis. When these cells are not promptly disposed of they become necrotic, progressively leading to the formation of a thrombogenic and pro-inflammatory necrotic core containing cholesterol crystals [58].

The Overgrowth and Instability of Plaques and Subsequent Acute Cardiovascular Events

During plaque growth and expansion, SMC migrate from the media to the intima and proliferate, forming a fibrous cap from extracellular matrix deposition, where activated lymphocytes and calcium deposits are found. Although plaques can grow to a sufficiently large size to compromise blood flow, most of their clinical complications are attributable to arterial occlusion due to plaque erosion or rupture. Vulnerable plaques are typically large with a necrotic core covered by a thin fibrous cap and contain high levels of inflammatory immune cells [122]. The thin fibrous cap easily ruptures, as there are areas of the plaque where few SMC are present, and macrophages exist in abundance. This is because inflammatory cells cause the death of SMC, which are the main source of collagen that produce and maintain the fibrous cap. PAF is also implicated in the release of several proteases from leukocytes, such as elastase, that degrade the vessel’s extracellular matrix components of the intima, which may lead to plaque rupture [58]. As the plaque continues to develop it can become unstable and rupture, leading to a major cardiovascular event such as myocardial infarction, stroke, or congestive heart failure, depending on the location of the rupture.Platelets are critical effectors in the development, progression, and resolution of the final stages of atherosclerosis, and plaque rupture, which is responsible for acute coronary disorders and stroke, not only due to their direct effects on the endothelium but also by acting as a ‘bridge’ for other cells within the vascular system [119,121]. Plaque rupture occurs under inflammatory cascades and atherothrombosis through an interplay of platelet-leukocyte aggregates. Upon vessel injury (i.e., plaque rupture), platelets readily adhere to damaged endothelium, and this binding event facilitates further activation and discharge of activating factors stored in platelet granules. Such platelet secretory components include membrane ligands and several chemokines such as PAF that play a role in further recruitment of leukocytes, additional platelets, or other blood cells to the vessel wall [121]. Platelet adhesion under conditions of high shear stress, which occurs in stenotic atherosclerotic arteries, is central to the development of arterial thrombosis. Therefore, precise control of platelet adhesion must occur to maintain blood fluidity and to prevent thrombotic complications [119].

Concluding Remarks on PAF in Atherosclerosis and CVD

The potent pro-inflammatory mediator, PAF, and its related PAF/PAF-R pathways are key-junctions of the inflammatory milieu during all stages of atherosclerosis and subsequent CVD. Some biochemical mechanisms involved include the pro-inflammatory induction of endothelial dysfunction, oxidative and nitrosative stress, increased platelet reactivity, recruitment/tight-adhesion, and trans-endothelial cell migration of inflammatory cells from the circulation, differentiation of pro-inflammatory monocytes to inflammatory macrophages, induction of macrophage uptake of Ox-LDL, foam cell formation, induction of plaque growth, plaque instability that leads to eventual plaque rupture, and subsequent cardiovascular events. Outcomes from multiple animal model experiments and several clinical studies have also outlined the crucial role of PAF in atherosclerosis due to its elevated levels and its inflammatory interplay and crosstalk with several cells in the pathogenesis of cardiovascular disorders. Clinical studies that have evaluated the role of PAF as a predictor of CVD have also been reviewed [89].PAF-R antagonists have been tested with promising results [134,135,136,137,138,139,140], however the most prominent beneficial outcomes against atherosclerosis development and CVD were found when food-derived PAF inhibitors such as those present in the foods of the Med-diet. These molecules beneficially inhibit PAF activities and modulate its metabolism towards homeostatic PAF levels [103,140,141,142,143,144,145]. Many of these components are present in olive oil, wine, fish, and dairy products (Table 1). Interestingly, the administration of polar lipid extracts from fish or olive oil to hypercholesterolemic rabbits lead to the regression of atherosclerotic plaques [103,142,143,144,145]. These results clearly outline that targeting inflammation and its key-junctions such as the PAF/PAF-R pathways and PAF metabolism provide beneficial outcomes against atherosclerosis and CVD, even without targeting hypercholesterolaemia. Thus, by targeting inflammation, the cause of these disorders through non-toxic approaches such as the Med-diet and by not targeting single risk factors (such as hypercholesterolaemia) seems to provide preventive and protective beneficial results against atherosclerosis and CVD.

3.2.2. The Role of PAF in Cancer and Metastatic Angiogenesis

Cancer is the second leading cause of death in developed countries. New blood vessel formation penetrating solid tumours seems to be required for their growth and metastasis. Production of PAF and overexpression of PAF-R are implicated in the tumour-endothelium interplay during cancer growth, invasion, and metastasis in several types of cancer [57,114,169,170,171]. PAF and PAF-R are also involved in tumour growth that is associated with immunosuppression [172,173,174], while the crosstalk between PAF/PAF-R pathways and growth factors receptors pathways suggests a potentially important signalling link between inflammatory and growth factor signalling in cancer [173,174,175].It is not yet fully understood whether the initial levels of PAF in the tumour microenvironment originate from migrated inflammatory circulating cells as a response, or by activated endothelial cells in the vessels neighbouring tumours, or by the tumour cells themselves. However, there is correlation between the malignancy of cancer cells and PAF production and PAF-R expression. It seems that the production and accumulation of PAF in the tumour microenvironment originates from the coexistence of two or of all these procedures and/or by the inactivation of PAF-AH. For example, the PAF basic biosynthetic enzymes such as LPCAT1 (an isoform of lyso-PAF-AT) are overexpressed in several cancer cells and correlated with cellular invasiveness and migration. Therefore, LPCAT1 seems to contribute to tumour growth and metastasis in these types of cancer [176,177]. Moreover, endothelial cell PAF production results in enhanced inflammatory cell recruitment, while endothelial accumulation of PAF by PAF production and inactivation of PAF-AH plays also a role in cancer cell migration to distal locations [178]. In addition cigarette smoking, a classic risk factor for several cancers, contributes to metastatic disease via production of PAF and PAF-like molecules in lung tumours [174], while smoking related inhibition of breast cancer cell PAF-AH results in PAF accumulation and a subsequent increase in cell motility, tumour growth, and metastasis [178,179].Independently of the origin, the presence of PAF in the microenvironment of tumours activates cancer cells and endothelial cells to further amplify the production of both PAF, angiogenic factors, and increased expression of their receptors on cell-membranes, including the PAF-receptor, leading to a PAF cycle and further induction of several PAF/PAF-R related cascades. These cascades, in coordination with angiogenic cytokines and growth factors, enhance the initial signal and induce morphological alterations and cellular activities such as growth proliferation and motility, expression of adhesion molecules, extracellular matrix breakdown, migration, and endothelium reorder that leads to the formation of distinct neoplastic vessels in the tumour microenvironment [57]. All of the above result in the onset and development of tumour-induced angiogenesis and metastasis [57]. For example, in pancreatic cancer, PAF overexpression leads to cell proliferation and tumourigenesis through the PAF/PAF-R related MAPK signalling pathway, causing neoplasia [170]. In addition, PAF and PAF-like molecules are in part transported by tumour-derived extracellular vesicles, which play an important role in intercellular communication through PAF-R expressed by a variety of microenvironmental cells and endothelial cells, favouring metastasis [172]. Apart from its crucial role in cancer metastasis, which has been extensively reviewed [57], recent outcomes have demonstrated that PAF is also implicated in immunosuppression-related cancer induced by UV-irradiation, in which UV-induced production of PAF and PAF-like molecules and the expression of PAF-R activates systemic immune suppression and delays DNA repair [93].On the other hand, PAF and its receptor have been beneficially associated with cell survival during radiotherapy or chemotherapy, by proliferative signals on the surviving cells that are induced by apoptotic cells. These signals take place through mechanisms dependent on the activation of PAF-R related pathways of NF-kB, such as up-regulation of anti-apoptotic factors and decrease of the cytotoxic effect of chemotherapeutic agents, thereby contributing to cell survival [172]. However, recent studies have demonstrated that during cancer therapies (i.e., irradiation of carcinoma cells or chemotherapy), PAF-R ligands can be generated that further aggravate immune suppression and, when bound on the PAF-R of cancer cells, induce anti-apoptotic factors that protect the tumor cells from death induced by these treatments, while the combination of radiotherapy with PAF-R antagonists could be a promising strategy for cancer treatment [173,180].In several cancer types, PAF through the NF-kB pathway controls the expression of genes that take part in processes that lead to metastatic angiogenesis on one hand, while on the other hand it results in apoptosis of cancer cells, during the immune response and haematopoiesis during chemotherapies and radiotherapies [57]. It seems that PAF is a unique growth regulator with apparently diverse functions; PAF, like NF-kB, seems to promote distinct biological processes, and these dual actions of PAF may relate to the point of action in the cell cycle [57]. The timing, space, and quantity of its production play a significant role in the malignant or beneficial direction of its effects. Understanding how conditions and factors that control timing, location of activity, and the quantity of PAF levels and how these relate to the metabolic enzymes of PAF is of great importance.PAF-R antagonists have exhibited promising results in vitro and in vivo as anti-angiogenic molecules in several cancer cells and tumours, but also by reducing persistent pain during cancers [57,114,181,182]. In addition, the combination of chemotherapy and classic PAF-R antagonists seems to reduce the tumour volume and cause higher tumour regression when compared to each treatment alone [172,180]. Recently, synthetic glycosylated alkyl-phospholipids that act as PAF agonists and antagonists have exhibited promising antiproliferative outcomes and are now regarded as and can be new class of anti-tumour drugs [183]. However, apart from using synthetic or classic PAF antagonists, a dietary profile rich in bioactive molecules and food-derived PAF inhibitors such as those present in foods of the Mediterranean diet seems to provide beneficial preventive and protective effects against development, growth, and metastatic manifestations of cancer cells by inhibiting PAF activities and/or modulating its metabolism towards homeostatic PAF levels [57,137] (Table 1).

3.2.3. The Role of PAF in Glomerulosclerosis and Renal Disorders

PAF has been characterised as one of the main inflammatory mediators implicated in renal pathophysiology [184]. Production of PAF in the kidney can potentially be attributed to infiltrating inflammatory cells, but mostly to resident renal cells such as the mesangial cells of glomeruli [81,185]. Once synthesised, PAF does not accumulate in renal cells, but it is secreted and thus affects mesangial cells, neighbouring podocytes, and other infiltrating cells by binding to its receptor and inducing PAF/PAF-R pathways. In the kidney, PAF-R mRNA is ubiquitously expressed, and a gradient of its expression levels seems to exist; it is higher in the renal cortex, lesser in the outer medulla, and much lesser in the inner medulla, while within the nephron, the glomerulus demonstrates the highest PAF-R expression [78]. PAF infusion affects renal hemodynamics and glomerular permeability, resulting in changes in filtration rate and proteinuria [78].Apart from the physiological effects of PAF, its increased levels and overexpression of PAF-R in kidney are involved in the pathogenesis and progression of renal damage and acute renal failure [78,184,186,187]. Thus, PAF is implicated in antibody- and complement-mediated glomerular injury, in antithymocyte antibody-induced glomerular damage and other experimental models of immune renal damage, and in patients with lupus nephritis and IgA nephropathy [78]. PAF participates in the development of kidney graft dysfunction, namely, transplant rejection chronic transplant nephropathy and immunosuppressive drug-mediated nephrotoxicity [78]. PAF is also implicated in drug-related renal damage of different causes, such as cyclosporin A, glycerol, gentamicin, and cisplatin [78].However, the most important role of PAF in renal dysfunction is its implication in the onset and progression of glomerulosclerosis, a renal disorder that shares common features with atherosclerosis and can lead to organ failure. Crosstalk between several renal cells of the glomeruli, such as the mesangial cells and podocytes, takes place during this disorder and the PAF/PAF-R pathways form key junctions during all steps. It has been proposed that PAF might be one of the chemokines released by mesangial cells that mediate their communication with podocytes. PAF enhances its own receptor expression [188], through which it stimulates multiple downstream inflammatory signalling pathways, mostly in mesangial cells, leading to the release of AA metabolites and subsequent prostanoid and thromboxane generation, leukocyte recruitment, mesangial cell contraction, intracellular lipid accumulation, and transforming growth factor (TGF)-β mediated upregulation of extracellular matrix production. All of these molecular events potentially culminate in the development of glomerulosclerosis and fibrosis, which are key feature of progressive renal disease, regardless of the primary cause [78,188,189]. In addition, PAF promotes inflammatory infiltration of the glomerulus, since it functions as a chemoattractant, and it increases adhesion of polymorphonuclear leukocytes and monocytes to mesangial cells through integrins [78]. PAF increases the expression of the LDL-receptor and scavenger receptors in mesangial cells, and thus causes an increased uptake of lipids and their accumulation in mesangial cells, leading to the formation of foam cells, which is an important stage of glomerulosclerosis and a key factor that participates in the initiation and progression of lipid-mediated renal injury [78,188].Several PAF-R antagonists have been used in several of the aforementioned renal disorders with promising results [78,137]. However, apart from using classic PAF antagonists, recent results have highlighted the protective role of a dietary profile rich in bioactive molecules, antioxidants, and food-derived PAF inhibitors such as those present in the Mediterranean diet through beneficially inhibiting PAF activities and/or modulating its metabolism towards homeostatic PAF levels [80,81] (Table 1). In addition, the use of vitamin D or vitamin-D analogues as treatment in haemodialysis patients has also exhibited similar beneficial effects, since such a treatment strongly inhibits PAF and thrombin activities, affects PAF metabolism towards equilibrating PAF levels, and reduces circulating levels of IL-8, IL-1β, and TNF-α [79]. As reducing dietary cholesterol levels may be ineffective, such outcomes have further supported the notion of using full-fat products such as dairy products and non-low-fat products, since the full-fat dairy products exhibit higher bioavailability of high-value nutrients such as bioactive polar lipids and vitamin D, which both possess strong anti-inflammatory and protective properties [3].

3.2.4. The Role of PAF in Cerebrovascular and Central Nervous System Disorders

PAF and the PAF/PAF-R pathways are also present in the CNS, where they exhibit a number of diverse physiological and pathological functions. PAF is synthesised in neuronal cells throughout the CNS, while these cells also express the PAF-R [190,191]. When present at normal concentrations, PAF is a modulator of many CNS processes, ranging from long-term potentiation to neuronal differentiation [113,191]. Excessive levels of PAF appear to play an important role in neuronal cell injury and in various inflammation-related CNS pathological conditions, such as neuroinflammatory cascades implicated in depression and neurodegeneration, Alzheimer’s disease, stroke, ischemia-reperfusion injury, spinal cord injury, multiple sclerosis, Parkinson’s disease, neuropathic pain, epilepsy, central malaria, meningitis, depression, cognitive deficits, and HIV-induced neurotoxicity [190,191,192]. Increased PAF synthesis through the PAF/PAF-R pathways can cause a severe inflammatory response, reduction of biological membrane integrity, ROS and RNS formation, expression and release of cytokines, alterations in blood–brain barrier permeability and the permeability of blood vessel walls, activation and recruitment of inflammatory and immune cells, secretion of cell-specific proteins, induction of cell apoptosis through specific signalling pathways, and other pathological responses [113,190,191,192,193]. PAF accumulation in CNS diseases exacerbates the inflammatory response and pathological consequences, while application of PAF inhibitors or PAF-R antagonists significantly reduces inflammation, protects cells, and improves the recovery of neural functions by blocking the PAF pathway [191,192,194]. Several PAF inhibitors of natural origin have also exhibited beneficial outcomes in CNS disorders, especially ginkgolides that are derived from Ginkgo biloba [137,195]. However, further studies are required to establish the mechanisms surrounding how a healthy diet can improve systemic inflammation associated with the PAF pathway and CNS disorders.

3.2.5. The Role of PAF in Allergies and Asthma

Anaphylaxis is defined as a severe, life-threatening, systemic or general, immediate reaction of hypersensitivity, with repeatable symptoms caused by a dose of stimulus that is well tolerated by healthy persons [196,197]. Recently, PAF and PAF-AH have been reported as clinically valuable biomarkers of anaphylaxis [196], since PAF produced and released by mast cells, basophils, neutrophils, eosinophils, fibroblasts, platelets, endothelial cells, and even cardiac muscle cells plays an important role in anaphylaxis and several other allergic reactions, from allergic rhinitis to asthmatic complications [67,196,197,198,199,200,201,202]. Eosinophils, mast cells, and basophils are implicated in allergies, and they have the capacity to influence each other’s functions through a crosstalk, where other mediators such as PAF are also implicated [198,199,200,203]. PAF increases the production of eicosanoids, ROS, cytokines, growth factors, platelet-derived growth factor (PDGF), RANTES, and degranulation of eosinophils, while it also acts as a chemoattractant for these cells, and, via integrins, it increases their adhesion to vascular endothelium. Mast cells not only produce PAF, but they can also be activated by it through the PAF/PAF-R pathways. Thus, exposure of mast cells to PAF leads to the induction of specific functions in these cells such as degranulation of their granules via neuropeptides and PAF-dependent release of histamine. In fact, the greater the levels of PAF in mast cells microenvironment, the more enhanced the release of histamine. At the same time, PAF-activated myocardial mast cells locally release factors responsible for cardiac dysfunction and hypotension that occur in severe anaphylactic reactions [197,200].Increased levels of PAF correlate with the severity of allergic systemic reactions. Thus, PAF has been found to be involved in several allergic and anaphylactic reactions and shock, in inflammation of bronchi and bronchial asthma and in asthmatic patients’ bronchoconstriction, in mucus hypersecretion, in allergic rhinitis, and in urticaria pathogenesis [200]. Several studies have shown that PAF can enhance obstructive changes of bronchi by stimulation of allergic inflammation of the respiratory tract epithelium, while PAF can also increase the permeability of skin’s capillaries and induces the development of wheals, flare, and inflammatory reactions in the skin through its interactions and crosstalk of the aforementioned inflammatory cells involved in these pathological conditions [200].The protective role of PAF-AH in reducing PAF levels is usually highly diminished through allergic reactions [196,200], while administration of recombinant PAF-AH in animal models exhibited protective results and reduced mortality due to anaphylactic reactions [196], implying that modulation of PAF metabolism towards homeostatic PAF levels can also provide beneficial outcomes in these disorders too. In addition, specific PAF-R inhibitors have been used in several allergy-related disorders [137], and even specific anti-allergic drugs were designed and are currently used according to their anti-PAF effects [204,205], while combination of PAF inhibitors with other therapies such as antihistamines provided better outcomes [137,198,199,201]. However, further studies are required to establish the potential of a healthy diet to improve systemic inflammation associated with the PAF pathway and allergic complications.

3.2.6. The Role of PAF in Chronic Infections and Inflammation-Associated Comorbidities

Inflammatory and immune responses are central to protecting against most infectious agents. However, the pathogenesis and tissue damage after infection are not usually related to the direct action microorganisms and of their replication, but instead to altered immune and inflammatory responses triggered following contact with the pathogen. Many diseases develop as an adverse consequence of an imbalanced inflammatory response; thus, chronic and unresolved infections are usually accompanied by chronic and unresolved inflammatory manifestations and comorbidities [206]. PAF and PAF-like molecules are implicated in inflammatory manifestations occurring in several infections [206,207], such as HIV [69,70,71,72,73,74,85], leishmaniosis [208], periodontitis [75,76,77], or even in sepsis [67,209]. The relationship between increased PAF levels, overexpression of PAF-R, and the PAF/PAF-R pathways with several other mediators such as cytokines and inflammatory cells leads to the progression of such diseases and their related comorbidities.The most common coexistent diseases associated with chronic infections are CVD, CNS disorders, and tumour malignancies, which are usually promoted by increased levels of PAF and PAF-related continuous and unresolved inflammation [57,67,68,69,70,71,72,73,74,75,76,77,85,208]. In addition, PAF seems to act in synergy with infectious agents to initiate and propagate the disease process, i.e., viral load in HIV-infected patients was positively correlated with PAF synthesis and levels, while viral products such as Tat-protein induce PAF synthesis and PAF-related HIV-induced non-AIDS comorbidities, such as CVD, Kaposi sarcoma, neurodegeneration, and dementia [69,70,71,72,73,74].Several PAF inhibitors have been used in infectious diseases with promising results, mostly in relation to their deterioration of the PAF-related chronic inflammatory manifestations [67,71,74,85,137,207,209,210,211]. However, in the case of severe sepsis, clinical trials using recombinant human PAF-AH or PAF-R antagonists failed to reduce the mortality of severe septic patients, although a substantial reduction in organ dysfunction was achieved [206]. Drugs administrated in such infectious pathologies have also been thoroughly screened for potential dual actions against both the infectious agent and PAF activities and synthesis. Several antiretrovirals and their combinations in highly active antiretroviral therapy have been found to exhibit beneficial outcomes in HIV infected patients through their capabilities to inhibit PAF activities and to influence PAF metabolism towards reduction of PAF levels in vitro and in vivo, while similar outcomes have also been found for several antibiotics [68,69,71,73]. Nevertheless, inhibition of PAF activities and modulation of PAF metabolism towards homeostatic PAF levels seem to be useful therapeutic targets with which to interfere with inflammatory damage that follows an infection, and thus they may reduce the risk of several comorbidities in infectious disorders. Although there are several studies published on the importance of a healthy diet for infection prevention, further studies are required to establish the potential role of healthy eating to improve systemic inflammation associated with the PAF pathway and related complications during chronic infections.

3.2.7. The Role of PAF in Various Inflammation-Related Chronic Diseases

PAF has also played a role in several other inflammation-related chronic diseases and their related comorbidities, including types I and type II diabetes mellitus [212,213,214], acute pancreatitis [215,216], liver injury [217], inflammation-related intestine tissue dysfunction such as necrotising enterocolitis [218,219], inflammatory ocular diseases [220], vascular dysfunction during acute lung injury [221], and autoimmune disorders, such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, and Crohn’s disease [222,223,224].Several PAF inhibitors have been used in these inflammation-related diseases with promising results [137,216,217,222,225,226]. These effects were mostly due to the deterioration of PAF-related chronic inflammatory manifestations present in these disorders. However, apart from using synthetic or classic PAF antagonists, a dietary profile rich in bioactive molecules, antioxidants, and food-derived PAF inhibitors such as those present in foods of the Mediterranean diet may provide beneficial preventive and protective effects against these diseases too, through beneficially inhibiting PAF activities and/or modulating its metabolism towards homeostatic PAF levels. For example, the consumption of components of the Med-diet or a traditional Greek Mediterranean diet can reduce PAF-related inflammatory outcomes such as platelet activity in patients suffering from type II diabetes mellitus and metabolic syndrome, but also in healthy subjects. This has been attributed to the presence of PAF inhibitors among other possible effects, and these effects can occur over a short period of time [227,228,229]. In addition, the use of probiotics has exhibited beneficial effects against necrotising enterocolitis [218]; this is unsurprising, as fermented dairy products, which are also components of the Med-diet, are rich in PAF inhibitors and have also exhibited beneficial outcomes in several inflammation-related intestine dysfunctions [3].

3.3. Targeting the PAF Pathways and Metabolism – Beneficial Outcomes of the Mediterranean Diet

Common junctions in the mechanistic crosstalk of inflammatory mediators, signalling pathways, and cellular interactions that occur during chronic and unresolved inflammatory manifestations seem to be promising therapeutic targets for the prevention and treatment of inflammation-related chronic diseases. Drug-based therapeutic interventions targeting inflammatory mediators such as cytokines (i.e., by using specific antibodies against pro-inflammatory cytokines and their receptors) and eicosanoids (i.e., by using specific inhibitors of COX-1 and COX-2) have also been proposed, and relative trials such as CANTOS are still in progress. However, such approaches can sometimes provide undesirable effects and may leave the individual immunocompromised and at a greater risk of infections, since disruption of the physiological balance seems to be a risky strategy [230,231], which is clearly behind the multifaceted effects of such mediators.On the other hand, since PAF and its related inflammatory cascades belong to the most vital joint mechanistic pathways of inflammation-related chronic disorders, the exploration of possible therapeutic approaches targeting PAF and its related pathways may provide better outcomes. Focus initially was given to the PAF/PAF-R interaction, thus inhibiting the exacerbation of the complex PAF inflammatory pathways [89,134,135,136,137]. There are several agonists of synthetic and natural origin [57,89,134,135,136,137,140,232], which can competitively or noncompetitively displace PAF from its binding sites on PAF-R and thus directly inhibit the PAF/PAF-R related pathways and PAF activities. Furthermore, other similar molecules can indirectly affect the PAF/PAF-R pathways by affecting the up-stream and/or downstream microenvironment of PAF-R, lipid, rafts, and other related cellular receptors.Even though such specific PAF antagonists for the PAF/PAF-R pathway have exhibited promising results, the most prominent beneficial effects have been derived from polar lipids and polar lipid extracts derived from several foods, particularly from foods in the Med-diet (Figure 1B and Table 1) [56,57,80,81,103,142,146,147,148,149,150,151,152,153,154,155,156,157,158,159,162,163,164,165,233,234]. These Med-diet polar lipids exhibit in vitro and in vivo anti-inflammatory activities through either directly or indirectly inhibiting the PAF/PAF-R pathways and thus PAF activities, but also by downregulating its levels through modulating the activities of key metabolic enzymes of PAF by either upregulation of the PAF catabolic enzymes and/or the downregulation of the basic PAF biosynthetic enzymes (Figure 2C and Figure 3C, and Table 1) [57,80,81,103,146,148].Notably, the uptake of such dietary polar lipids seems to beneficially affect the functionality of HDL lipoproteins, especially in atherosclerotic conditions. HDL has been characterised as the ‘good’ cholesterol, since not only does it remove excess cholesterol from the blood stream and from atherosclerotic plaques, but it has also exhibited anti-inflammatory and antioxidative properties through a plethora of cardioprotective enzymes bonded in HDL, including the aforementioned PAF-AH enzyme activity, which is the main catabolic enzyme of PAF [110]. These HDL-associated activities contribute to the maintenance of endothelial cell homeostasis, which protects the cardiovascular system [235]. Plasma PAF-AH is also found in atherosclerotic lesions, since it comigrates there along with the lipoproteins (i.e., LDL), where it is incorporated. Plasma PAF-AH (Lp-PLA₂) mainly plays an anti-inflammatory role in leukocyte/platelet/endothelium activation and seems to suppress atherogenic changes in plasma lipoproteins (such as LDL) by promoting the catabolism of PAF and by removing oxidised phospholipids present in Ox-LDL, including oxidised phospholipids that mimic PAF, which are generated by oxidative modifications of lipoproteins such as LDL during pro-atherogenic and atherosclerotic events [107,109,110]. Thus, during inflammatory cascades that cause increased PAF levels, this isoform of PAF-AH (LpPLA₂) seems to be activated as a homeostatic mechanism to downregulate these events by downregulating the levels of PAF and oxidised phospholipids as a terminator signal [236]. However, during persistent and prolonged inflammatory cascades and persistent oxidation of plasma lipoproteins, plasma PAF-AH is progressively inactivated (plasma PAF-AH is incorporated mainly in LDL) and loses its capacity to protect against the pro-inflammatory actions of PAF and PAF-like lipids [98]. Because of that, but also because of the activities of the oxidised sub products of PAF-AH actions in LDL oxidised phospholipids, the use of plasma PAF-AH as an atherogenic biomarker and therapeutic target has been debated [109,236].Nevertheless, HDL and its enzymes, including PAF-AH, seem to protect against these manifestations. The focus has been placed on increasing HDL levels as one of the main goals of dietary interventions and drug administration for cardioprotection [110]. Dietary intake of bioactive polar lipids, particularly those baring ω-3 PUFAs, increase HDL levels and the incorporation of such anti-inflammatory and antioxidant dietary polar lipids to HDL, thus providing an additional protective mechanism by increasing plasma PAF-AH activity and protecting the HDL enzymes (such as PAF-AH) from oxidation-related inactivation. This is in agreement with the beneficial in vitro and in vivo effects of several dietary polar lipids, especially on PAF metabolism and HDL biofunctionality [56].PAF can generate ROS, and oxidative stress is a key feature of the atherothrombotic processes in the pathology of CVD. Therefore, it is important to recognise that foods of the Med-diet such as fruit and vegetables are high in chemical constituents, many of which are regarded as powerful antioxidants, such as vitamins A, C, and E [237]. Despite positive findings from in vitro studies, clinical trials have consistently failed to show a benefit for the use of antioxidants, as associations between plasma concentrations of antioxidant vitamins and protection against CVD have proved elusive, and large interventional trials have failed to conclusively show any benefit of their administration [238,239,240,241]. Despite this, the European prospective investigation into cancer and nutrition (EPIC) Norfolk study found that increased plasma concentrations of vitamin C were inversely associated with CVD-related mortality and all-cause mortality. The study found that this increase was due to increased intake of fruit and vegetables, which led to an approximate 20% decrease in CVD mortality [242]. However, a meta-analysis has shown that vitamin C supplementation did not reduce cardiovascular events; thus, the antioxidant effects of vitamin C were not responsible for the beneficial effects of increased consumption of fruit and vegetables [243]. A large-scale, 20-year study found that diets rich in vitamin C were associated with a lower incidence of stroke, but no coronary heart disease in the elderly [244]. Considering these findings, it may be the case that vitamin C may not be the active agent that induced the effects witnessed in the Norfolk study, but although eating fruit and vegetables will increase plasma vitamin C levels, the effects observed may be through other fruit- and vegetable-derived nutrients [241], or synergism between multiple nutrients that affect different mechanisms including inflammation through the mechanisms of the PAF pathways [245].The bioavailability of vitamins, phenolic compounds, and other antioxidants is often cited as the main reason that in vitro and ex vivo studies do not seem to agree [237]. For instance, some antioxidants such as phenolic compounds are effectively screened out by the gut of rapidly metabolised and excreted [246]. Plasma concentrations of phenolic compounds are typically in the nanomolar range—too low to have a direct impact on antioxidant capacity [241]. However, many of these antioxidant molecules do seem to possess beneficial effects upon consumption, including the idea that they induce indirect antioxidant activity by acting as a mild toxin to stimulate a general xenobiotic and/or an antioxidant response [237]. Further research is required to elucidate the effects of certain biomolecules against ROS and inflammatory pathways. Overall, the protective outcomes of the adoption of Med-diet towards chronic diseases seem to be associated with the pleiotropic beneficial effects of its bioactive microconstituents that are not only limited to increasing plasma-HDL levels, functionality, and providing better stability against oxidation, but mainly on their effects on the levels, activities, and metabolism of key-inflammatory mediators such as PAF [56,57]. However, more in vivo results are needed in several chronic disorders and their inflammation-related manifestations in order to further support these findings. In particular, clinical trials implementing dietary patterns such as the Med-diet that are rich in bioactive polar lipids interacting with the PAF/PAF-R pathways and metabolism are required to gain further insight into the role of PAF in chronic diseases.

high low‐density lipoprotein cholesterol to high‐density lipoprotein cholesterol ratio as a potential risk factor for corticosteroid‐induced osteonecrosis in rabbits | Rheumatology

Abstract

Objective. This study was designed to determine the potential risk factors for corticosteroid‐induced osteonecrosis (ON) based on lipid metabolism, using a rabbit ON model.

Methods. Blood samples were obtained from 38 rabbits, which then received a single intramuscular injection of 20 mg/kg methylprednisolone acetate. Four weeks after the injection, the femora and humeri were examined histopathologically for the presence of ON, and the sizes of the bone marrow fat cells were also measured.

Results. Rabbits with and without ON differed significantly in the ratio of low‐density lipoprotein cholesterol to high‐density lipoprotein cholesterol (LDL/HDL cholesterol ratio), which is considered to be a serological marker of lipid transport (P=0.026). The marrow fat cells were significantly larger in the rabbits with ON than in those without ON (P<0.0001).

Conclusion. A higher LDL/HDL cholesterol ratio was significantly associated with the development of ON, and such an elevated ratio may partly contribute to the increased size of marrow fat cells.

Non‐traumatic osteonecrosis (ON) of the femoral head is a devastating disease, and generally occurs in the third to fifth decades of life [1, 2]. Total hip replacement has been one of the major therapeutic options [2]; however, a higher rate of early failure has been reported in younger ON patients [3, 4]. Prevention is thus the ideal strategy, and therefore the possible risk factors have been investigated in order to identify patients susceptible to ON.

ON is known to occur in patients who have received corticosteroids for the treatment of underlying diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis and leukaemia [1, 2, 5]. It would therefore be ideal if we could assess the risk of ON prior to corticosteroid treatment. Recently, a high level of lipid transport has been reported in human ON cases [6]. Increased size of bone marrow fat cells has also been reported to be associated with corticosteroid‐induced ON [7].

This study was designed to determine the potential risk factors for corticosteroid‐induced ON in rabbits, based on lipid metabolism.

Materials and methods

The rabbit model of corticosteroid‐induced ON that we used in this study has been described in a previous paper [8].

Animals

Adult (growth plate closed) male Japanese white rabbits (Kyudo, Tosu, Japan), weighing 3.2–3.8 kg, were used at the Animal Centre of Kyushu University and were maintained on a standard laboratory diet and water. The ages of the rabbits ranged from 28 to 31 weeks. All experiments were reviewed by the Common Ethics Committee for Animal Experiments at Kyushu University, and were conducted in accordance with the Guidelines for Animal Experiments of Kyushu University, Japanese law (no. 105), and the notification (no. 6) of the government and the Committee on Ethics in Japan.

Haematological examination

Blood samples were obtained from all rabbits in a fasting state between 7 and 9 a.m. Haematological and chemical evaluations were made for 15 serological factors, including the white blood cell count, red blood cell count, haemoglobin, haematocrit, platelets, total cholesterol, triglycerides, very low‐density lipoprotein (VLDL), chylomicron, ratio of low‐density lipoprotein cholesterol to high‐density lipoprotein cholesterol (LDL/HDL cholesterol ratio), free fatty acids (FFA), glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, C‐reactive protein (CRP) and fibrinogen.

The total cholesterol, triglyceride, low‐density lipoprotein cholesterol and FFA levels were measured by enzymatic methods [9–12]. High‐density lipoprotein cholesterol was measured with polyethylene glycol‐modified enzymes and sulphated α‐cyclodextrin [13]. VLDL and chylomicron were measured by the turbidimetric method [14]. Fibrinogen was measured using a thrombin reagent kit (Dade Behring, Newark, DE, USA). CRP was measured by a turbidimetric immunoassay [15].

Treatment

After blood samples had been obtained from all rabbits, 38 rabbits were injected once with 20 mg/kg body weight methylprednisolone acetate (MPSL) (Upjohn, Tokyo, Japan) into the right gluteus medius muscle. All rabbits were killed 4 weeks after the injection of MPSL. The animals were anaesthetized with an intravenous injection of pentobarbital sodium (25 mg/kg body weight) (Abbott, Chicago, IL, USA), and were then killed by aortectomy.

Tissue preparation

For light microscopic examinations, both femora and both humeri (a total of four bone samples) were obtained at the time of death, and were fixed for 1 week with 10% formalin–0.1 m phosphate buffer, pH 7.4. The bone samples were decalcified with 25% formic acid for 3 days and were then neutralized with 0.35 m sodium sulphate for 3 days. The bone samples from the femora and humeri were cut along the coronal plane in the proximal one‐third and the axial plane in the distal part (condyle). The specimens were embedded in paraffin, cut into 4 μm sections, and stained with haematoxylin and eosin.

Evaluation of ON

The whole area of the proximal one‐third of both femora and humeri and whole sections of the condyles of both femora and humeri, a total of eight regions, were examined histopathologically for the presence of ON. ON was assessed blindly by three authors (KM, TY, TI) without knowledge of the haematological results. The diagnosis of ON was based on the diffuse presence of empty lacunae or pycnotic nuclei of osteocytes in the bone trabeculae, accompanied by surrounding bone marrow cell necrosis [8, 16]. All rabbits that had at least one osteonecrotic lesion out of eight areas examined were considered to be osteonecrotic (ON⁺) while those with no osteonecrotic lesions were considered to be non‐osteonecrotic (ON⁻).

Measurement of intraosseous lipid deposition

As described in a previous report [7], intraosseous lipid deposition was quantitatively determined by measuring the size of the bone marrow fat cells using a Power Macintosh computer and NIH image software [17]. The fat‐cell size was calculated as the average of the greatest diameters of 25 fat cells in four randomly selected locations in the proximal one‐third of the right femur. Briefly, an image of the sections was obtained with a camera and was directed electronically to the image processor, where it was digitized, and then analysed by computer. The projected image of the fat cells displayed on the video monitor was measured using an interactive mousepad tracing instrument, while the corresponding morphometric data were processed automatically by the computer system. Fat cells that had undergone necrosis were excluded from the evaluation of fat‐cell size. The metaphyseal and/or diaphyseal regions were examined because ON has been seen in these areas in this rabbit model [8].

The repeatability of the measurement method of marrow fat‐cell size was determined by having two authors (KM and TY) measure each value of the 38 rabbits on two occasions at a 1‐week interval [18]. The interobserver differences (the differences between the measurements by KM and the other measurements by TY for the values in each rabbit) were the mean values of the differences in all rabbits. The intraobserver differences (the differences between two measurements at different times by KM for the same rabbit) were the mean values of the differences in all rabbits. The interobserver and intraobserver coefficients of repeatability were also calculated.

Statistical analysis

The data on the haematological examinations and fat‐cell sizes are given as the mean±s.d. All haematological data and fat‐cell sizes were compared between the ON⁺ and ON⁻ rabbits, using Student’s t‐test. For correlations between the LDL/HDL cholesterol ratio and the number of osteonecrotic lesions, we used the Spearman correlation coefficient. P<0.05 was considered to be significant. All analyses were performed using SPSS 6.1J on a Macintosh computer (SPSS Japan, Tokyo, Japan).

Results

Prevalence and location of ON

The incidence of ON⁺ rabbits was 29/38 (76%). ON was located in the metaphysis and/or the diaphysis, but not in the epiphysis.

Histopathological features

Macroscopically, ON in both the femur and humerus was observed in the metaphysis and/or the diaphysis as yellowish‐coloured areas. Histologically, ON lesions showed an accumulation of bone marrow cell debris and bone trabeculae demonstrating empty lacunae (Fig. 1A). The accumulation of serofibrinous exudate as part of a repair process was also seen around the necrotic area. Both the femur and the humerus of a corticosteroid‐treated rabbit that did not develop ON consisted of normal bone trabeculae and normal bone marrow cells (Fig. 1B). An intraosseous vein occluded by fat emboli was noted in the metaphysis of the femur in three rabbits with ON (Fig. 1C).

Fig. 1.

(A) Histological features of osteonecrosis in a corticosteroid‐treated rabbit. The bone trabeculae show empty lacunae, while the surrounding marrow tissue consists of necrotic marrow cell debris. Haematoxylin/eosin staining, 200× magnification. (B) Photomicrograph of a femur of a corticosteroid‐treated rabbit that did not develop osteonecrosis, which consists of normal bone trabeculae and normal bone marrow cells. Haematoxylin/eosin staining, 200× magnification. (C) The intraosseous vein is occluded by a fat embolus in the metaphysis of the proximal femur of a rabbit with osteonecrosis (arrow). Haematoxylin/eosin staining, 200× magnification.

Fig. 1.

(A) Histological features of osteonecrosis in a corticosteroid‐treated rabbit. The bone trabeculae show empty lacunae, while the surrounding marrow tissue consists of necrotic marrow cell debris. Haematoxylin/eosin staining, 200× magnification. (B) Photomicrograph of a femur of a corticosteroid‐treated rabbit that did not develop osteonecrosis, which consists of normal bone trabeculae and normal bone marrow cells. Haematoxylin/eosin staining, 200× magnification. (C) The intraosseous vein is occluded by a fat embolus in the metaphysis of the proximal femur of a rabbit with osteonecrosis (arrow). Haematoxylin/eosin staining, 200× magnification.

Haematological examination

A significant difference was observed in the LDL/HDL cholesterol ratio between the ON⁺ (0.44±0.10) and ON⁻ (0.34±0.14) rabbits (P=0.026). The remaining 14 serological factors, including cholesterol and triglyceride, showed no significant difference between the two groups (Table 1).

Correlation between the LDL/HDL cholesterol ratio and the number of osteonecrotic lesions

Multifocal ON lesions were identified in both the femur and humerus. The ON⁺ rabbits were found to have a mean of 2.4 sites (range 1–6) with ON. Ten rabbits showed one involved lesion, while 11 rabbits had two lesions, one rabbit had three lesions, three rabbits had four lesions, and four rabbits had six lesions. No rabbits had five, seven or eight ON lesions. A significant correlation was found between the LDL/HDL cholesterol ratio and the number of osteonecrotic lesions (Fig. 2; ρ=0.583, P=0.0004).

Fig. 2.

A significant correlation was found between the LDL/HDL cholesterol ratio and the number of osteonecrotic lesions (ρ=0.583, P=0.0004). The LDL/HDL cholesterol ratios of the rabbits without osteonecrosis are plotted at 0 on the abscissa.

Fig. 2.

A significant correlation was found between the LDL/HDL cholesterol ratio and the number of osteonecrotic lesions (ρ=0.583, P=0.0004). The LDL/HDL cholesterol ratios of the rabbits without osteonecrosis are plotted at 0 on the abscissa.

Table 1.

Results of the haematological examination^a

Table 1.

Results of the haematological examination^a

Measurement of intraosseous lipid deposition

The size of the marrow fat cells increased significantly more in the ON⁺ rabbits (diameter 58.8±6.7 μm) than in the ON⁻ rabbits (diameter 46.8±3.5 μm) (P<0.0001).

The mean interobserver and intraobserver differences of the measured variables were 0.09 μm (range −1.90 to 2.78; 95% confidence interval −0.33 to 0.51) and 0.06 μm (range −1.79 to 3.21; 95% confidence interval −0.31 to 0.43) respectively. The interobserver and intraobserver coefficients of repeatability were 2.57 and 2.26 μm respectively.

Discussion

Both hypercoagulability and hypofibrinolysis have been reported in human non‐traumatic ON cases, including a high plasminogen activator inhibitor [19], high lipoprotein (a) [19], and the presence of anticardiolipin antibodies [20]. These risk factors are useful when considering the pathophysiology of ON. However, the causality between these abnormalities and the development of ON or corticosteroid administration has not yet been fully clarified, because they were identified in patients who had either already developed ON or received corticosteroid treatment. Since the same dose of corticosteroids does not cause ON equally in every patient [5], there may be individual variations in susceptibility to the development of ON before starting corticosteroid administration. In this study, the serological factors were thus examined prior to the steroid administration, and correlated with the occurrence of ON 4 weeks after steroid administration. Assessment of the serological factors after steroid administration may be less important in order to determine a potential risk factor. Such a study design, in which the relationship between risk factors in a cross‐sectional survey and the subsequent occurrence of a disease is investigated, has also been employed in other studies [21–23]. In the Bogalusa Heart Study, baseline serum lipoprotein levels in cross‐sectional surveys were correlated with coronary artery fatty streaks at autopsy [21].

Ideally, blood samples should be collected from patients with collagen diseases before steroid treatment. Patients with SLE have been often used to investigate the pathogenesis of ON because they show a high frequency of ON [5]. The average incidence rate of SLE was reported to be 5.56 per 100 000 in the USA [24]. In order to detect the occurrence of ON, SLE patients receiving steroid treatment should be observed using magnetic resonance imaging for at least 6 months [25]. Considering both this relatively low incidence rate of SLE and the long follow‐up period, we estimate that it would take more than 2 yr to collect data on a sufficiently large number of newly diagnosed cases of SLE to reach statistical significance. Compared with such a clinical prospective study in man, an animal study is easier to conduct. Many rabbits can be used simultaneously and ON can be determined histologically 4 weeks after steroid administration. In addition, rabbits have been reported to be a good model for human pharmacokinetic studies of corticosteroids [26]. The rabbit ON model was thus used to assess the potential risk factors for ON in this study.

A high LDL/HDL cholesterol ratio is considered to reflect prominent lipid transport to the peripheral tissue [27–29]. Such lipid transport has been suggested to be a risk factor for human ON [6]. We thus consider that a high LDL/HDL cholesterol ratio may be predictive of human ON. Rabbit ON shows other similarities to human ON. First, the multifocal nature of the ON is similar to that in humans [1, 8, 30]. Secondly, the histopathology of ON in this model is characterized by empty lacunae accompanied by surrounding bone marrow cell necrosis and the resulting reparative changes, which are analogous to those in humans [8, 31]. These similarities suggest significant relevance of this animal model to human ON.

It should be noted that a high LDL/HDL cholesterol ratio does not necessarily correspond to a high serum level of cholesterol, since the serum cholesterol level reflects the total delivery to and from the peripheral tissues. In this study, no significant difference was seen in the levels of cholesterol and triglyceride between the ON⁺ and ON⁻ rabbits. However, significant lipid transport resulting from a high LDL/HDL cholesterol ratio may have led to at least a local (intraosseous) hyperlipidaemic state in the ON⁺ rabbits. This view is supported by the increased fat‐cell size of ON⁺ rabbits in this study, as well as other clinical and experimental studies of ON [32, 33]. Boskey et al. [32] specifically reported significant cholesterol deposition in surgically removed human osteonecrotic femoral heads. Kawai et al. [33] reported the relationship between a decrease in HDL associated with lipid deposition in bone tissue and the development of ON in heritable hyperlipaemic rabbits.

Regarding the pathogenesis of corticosteroid‐induced ON, the concept of increased bone marrow pressure has been proposed, in which initial ischaemia is produced by intraosseous circulatory disturbances which result from thrombi, fat emboli and/or increased marrow fat‐cell size [7, 34]. In this study, both the LDL/HDL cholesterol ratio and fat‐cell size were significantly higher in the ON⁺ rabbits than in the ON⁻ rabbits. Fat emboli were identified in three ON⁺ rabbits, while no fat emboli were found in ON⁻ rabbits. Based on these data, a higher LDL/HDL cholesterol ratio may partly enhance this corticosteroid‐induced circulatory obstruction, and thereby contribute to the development of ON (Fig. 3).

Although we have focused on lipid metabolism in this study, hypercoagulability and hypofibrinolysis have also been reported to play a causative role in human ON [19, 20]. It is postulated that these factors enhance the coagulability which leads to thrombosis. Corticosteroids are known to induce not only hyperlipidaemia but also a hypercoagulable and hypofibrinolytic state of plasma [35, 36]. The pathogenesis of corticosteroid‐induced ON is considered to be multifactorial, and it seems clear that no one factor adequately accounts for the development of ON [2]. It is therefore not surprising that both hyperlipidaemia (general or local) and coagulopathy may be closely associated with the development of corticosteroid‐induced ON.

Such a multifactorial nature of ON may partly explain why the LDL/HDL cholesterol ratio did not show a much better (lower) P‐value. A high LDL/HDL cholesterol ratio is considered to be a reasonable risk factor to understand the pathogenesis of ON. We thus consider that an association between the development of ON and a high LDL/HDL cholesterol ratio is essentially valid in spite of this relatively high P‐value.

There have been a few reports regarding the factors that contribute to the multiple‐site development of ON [37, 38]. LaPorte et al. [37] reported the relationship between multifocal osteonecrosis and corticosteroid therapy. Egan and Munn [38] demonstrated an association between the antiphospholipid antibody syndrome and multiple sites of ON. These studies offer additional evidence that systemic abnormalities may be associated with multifocal ON. A current animal study suggests that the systemic nature of prominent intraosseous lipid transport resulting from a higher LDL/HDL cholesterol ratio may contribute to the development of multifocal ON, as well as the development of ON itself.

In this study, all rabbits used were as similar as possible regarding gender, weight, diet and age. We thus consider that the rabbits were almost homogeneous in nature, and therefore the significant difference in the LDL/HDL cholesterol ratio is not considered to have been influenced by these confounding factors.

In conclusion, a high LDL/HDL cholesterol ratio was found to be significantly associated with the development of ON as a potential risk in corticosteroid‐treated rabbits. The concept of intraosseous lipid transport may be useful not only for assessing the potential risk of ON, but also for exploring its possible mechanism in the future.

Fig. 3.

Postulated pathogenesis of corticosteroid‐induced ON. Initial ischaemia is produced by an intraosseous circulatory obstruction with fat emboli and/ or increased bone marrow fat‐cell size, which subsequently leads to the development of ON. A higher LDL/HDL cholesterol ratio may partly enhance this corticosteroid‐induced circulatory obstruction.

Fig. 3.

Postulated pathogenesis of corticosteroid‐induced ON. Initial ischaemia is produced by an intraosseous circulatory obstruction with fat emboli and/ or increased bone marrow fat‐cell size, which subsequently leads to the development of ON. A higher LDL/HDL cholesterol ratio may partly enhance this corticosteroid‐induced circulatory obstruction.

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Trump gains weight, now considered obese; cholesterol down

WASHINGTON (AP) — President Donald Trump has put on some pounds and is now officially considered obese.

The White House on Thursday released results of his most recent physical, revealing that his Body Mass Index is now 30.4. That’s based on the fact that he’s now carrying 243 pounds on his 6-foot, 3-inch frame. That’s up from 236 pounds in September 2016 before he became president.

An index rating of 30 is the level at which doctors consider someone obese under this commonly used formula. About 40 percent of Americans are obese, and that raises their risk for heart disease, diabetes, stroke and some forms of cancer.

Trump doesn’t drink alcohol or smoke, but he’s not a big fan of the gym either. His primary form of exercise is golf. And he says he gets plenty of walking in around the White House complex.

As for his diet, Trump’s love of fast food remains. Last month, he invited the college football champion Clemson Tigers to the White House during the partial government shutdown. With the White House kitchen too understaffed to cater a meal, Trump stepped in: He ordered burgers, french fries and pizza.

Despite gaining four pounds from last year, Dr. Sean Conley, the president’s physician, said the 72-year-old president “remains in very good health overall.”

His resting heart rate is 70 beats a minute and his blood pressure reading was 118 over 80, well within the normal range.

Conley said routine lab tests were performed and Trump’s liver, kidney and thyroid functions are all normal as were his electrolytes and blood counts. An electrocardiogram, a test that measures electrical activity generated by the heart as it beats, remained unchanged from last year.

“Despite the fact that he’s obese, his blood pressure is normal,” said Dr. Mariell Jessup, the Heart Association’s chief science and medical officer.

Using the association’s heart risk calculator, “he has a 17 percent chance of developing cardiovascular disease in the next 10 years,” mostly because of his age and slightly elevated bad cholesterol, she said.

Modern-day presidents have undergone regular exams to catch any potential problems but also to assure the public that they are fit for office. Trump went to Walter Reed National Military Medical Center last week for his second periodic physical, which lasted about four hours. During his exam, he received a flu shot and an inoculation to help prevent shingles, a viral infection that causes a painful rash.

“I performed and supervised the evaluation with a panel of 11 different board-certified specialists,” Conley wrote in a memorandum to the White House. “He did not undergo any procedures requiring sedation or anesthesia.”

His cholesterol reading improved since last year.

At his physical in January 2018, his total cholesterol was 223, which his higher than recommended, even though he was taking a low dose of the statin drug Crestor to help lower so-called “bad” cholesterol and fats. Last year, his doctor said he would increase that dose in an effort to get Trump’s bad cholesterol reading of 143 down below 120.

Now, Trump’s total cholesterol is down to 196, yet his LDL or “bad” cholesterol is 122 — slightly elevated. Conley said he planned to increase the dosage of a statin drug to 40 milligrams a day to bring the president’s cholesterol reading down further.

Dr. Robert Eckel, a former American Heart Association president and cardiologist at the University of Colorado, said he would aim for an LDL below 100.

“Losing some weight would help modify some of the risk factors for heart disease,” Eckel said. “A 20- to 25-pound weight loss would be what I’d recommend if he were my patient. And that’s not a quick fix.”

___

Chief Medical Writer Marilynn Marchione in Milwaukee contributed to this report.

Impact of LDL-cholesterol Lowering on Platelet Activation – Full Text View

The primary goal is to assess the impact of Evolocumab therapy on platelet function of familial hypercholesterolemia (FH) patients in a randomized, double blind study. Evolocumab is a humanized monoclonal antibody that targets circulating PCSK9, increases hepatic LDL receptor, decreases plasma LDL cholesterol and reduces risk of cardiovascular events. Evolocumab (brand name Rapatha) has been approved by FDA along with diet and maximally tolerated statin therapy in adults with FH or atherosclerotic heart or blood vessel problems, who need additional lowering of LDL cholesterol.

The secondary goal is to determine if platelet activation or the response to Evolocumab therapy is modified by rs3184504 polymorphism. The investigators believe that these investigations will complement ongoing studies to demonstrate that Evolocumab reduces athero-thrombotic risk and aid the decision-making as to whether Evolocumab can reduce the atherothrombotic risk in acute coronary syndrome (ACS) patients.

Hyperlipidemia as exemplified by familial hypercholesterolemia is associated with increased platelet activation and an underlying pro-coagulant state. Hyperlipidemia primes platelets and increases platelet activation in response to various agonists. Plasma cholesterol levels appear to have a critical role in modulating platelet activity as hypercholesterolemia increases platelet activation more potently than hypertriglyceridemia. Increased platelet reactivity may contribute to the increased risk of atherothrombosis associated with hypercholesterolemia. Plasma levels of platelet activation markers such as thrombin-antithrombin complex (TAT), soluble P-selectin (sP-selectin), soluble CD40L (sCD40L) or P-selectin exposure at surface of platelets are increased in hypercholesterolemic patients. Increased levels of the platelet activation markers are associated with increased platelet membrane cholesterol content in hypercholesterolemia.Statins may show antithrombotic properties.

High Cholesterol Specialist – Frederick, MD: Primary Care Associates of Maryland: Family Medicine

What is cholesterol?

Cholesterol is a waxy substance found in fat. Your body produces cholesterol, and you take in additional cholesterol from the food you eat.

Cholesterol is used to help make cells, but when your body has too much cholesterol, the waxy substance sticks to your artery walls, causing them to narrow and making it harder for blood to pass, which can lead to a heart attack or stroke.

The providers at Primary Care Associates of Maryland use blood tests to check and monitor your cholesterol levels.

What is high cholesterol?

High cholesterol is determined by your total cholesterol number from your blood test.

• Desirable: Less than 200 mg/dl
• Borderline high: 200 mg/dl to 239 mg/dl
• High: Greater than 240 mg/dl

The total cholesterol count includes two types of cholesterol: low-density lipoproteins (LDL), referred to as bad cholesterol, and high-density lipoproteins (HDL), referred to as good cholesterol. In addition to your total cholesterol, your provider also wants you to pay attention to your LDL and HDL numbers.

Keeping your LDL levels less than 100 mg/dl and your HDL greater than 40 mg/dl can help to improve your health. 

What are the symptoms of high cholesterol?

There are no symptoms associated with high cholesterol. But some factors increase your risk of high cholesterol, including:

• Genetic predisposition
• Lack of physical activity
• Poor diet choices
• Obesity
• Diabetes
• Smoking
• Excess abdominal fat

If you are concerned about your cholesterol levels, or your predisposition for developing high cholesterol, schedule a consultation at Primary Care Associates of Maryland.

How can I lower my cholesterol levels?

Your provider will likely recommend a change in diet and your activity levels as your first steps for lowering your cholesterol. Your provider will work with you to create an individualized plan that fits your lifestyle and fitness level. A healthy diet and exercise plan can also promote weight loss, which helps reduce cholesterol.

If your numbers aren’t improved after altering your diet and activity levels, your provider may prescribe a cholesterol-lowering medication. 

There are several options, including:

• Cholesterol absorption inhibitors
• Statins
• Bile-acid binding resins
• Injectables

With the help of the skilled and dedicated providers at Primary Care Associates of Maryland, you can manage your cholesterol levels more effectively. 

What steps can I take to prevent high cholesterol?

High cholesterol is preventable. Steps you can take to reduce your risk include:

• Maintaining a healthy weight
• Not smoking
• Eating a diet rich in fruits, vegetables, whole grains, and lean proteins
• Exercising regularly

If you have concerns about your cholesterol and would like to get your numbers checked, call Primary Care Associates of Maryland or request an appointment online.

90,000 Cholesterol and Lipid Profile | Blood pressure

Contents

Executive Summary

There have been many studies with vegans measuring cholesterol, blood pressure, body weight, and other markers of various diseases. Most of these studies also looked at lacto-ovo vegetarians, fish eaters, and non-vegetarians. This article includes research dating back to 1980, as there has been little previous research involving vegans.

Lipid profile

Lipids are fat-soluble substances, including cholesterol and fatty acids. Blood lipid profile measurement mainly includes total cholesterol, LDL cholesterol (low density lipoprotein cholesterol), HDL cholesterol (high density lipoprotein cholesterol) and triglycerides.

Total cholesterol is an indicator for all types of blood cholesterol. Cholesterol is divided into types depending on the lipoproteins that carry it in the blood.Low-density lipoprotein (LDL) cholesterol is considered “bad” because it tends to accumulate on the walls of arteries, causing heart disease. High-density lipoprotein (HDL) cholesterol is considered “good” because it is carried away from the tissues for processing in the liver, where it is then broken down or excreted through the gastrointestinal tract as bile. Fiber (mostly soluble) can bind to cholesterol and excrete it through the stool.

There are also other lipoproteins such as very low density lipoproteins (VLDL).They are not covered in this article as they have not been studied extensively with vegans.

Cholesterol in the EPIC-Oxford study

The most recent EPIC-Oxford study on cholesterol compares vegetarians and non-vegetarians with a healthy lifestyle (41). The results are presented in Table 1 and show that vegans had rates 34 mg / dL and 23 mg / dL lower than non-vegetarians, men and women, respectively. The biggest differences were for non-HDL cholesterol.Adjusting the results for body mass index reduced the difference to 13% for men and 17% for women.

Vegans also had significantly lower levels of apolipoprotein B, which is believed to cause the buildup of fatty deposits in the arteries.

The study authors suggest that vegans had lower cholesterol levels due to lower body mass index, higher intake of polyunsaturated fat instead of saturated fat, and higher fiber intake.

Cholesterol in Western Vegans (1980 – 2002)

Between 1980 and 2002, 17 studies were conducted on cholesterol levels in Western vegans. The median cholesterol level for vegans was 160 mg / dL compared to 202 mg / dL for non-vegetarians. Table 2 shows the results of the study.

Cholesterol in US Vegans

Of the 17 studies shown in Table 2, 5 were with US vegans.Of these studies, the lowest average cholesterol was 135 mg / dL. The data from these 5 studies are detailed in Table 3. The mean total cholesterol level in 135 vegans was 146 mg / dL.

Triglycerides

Elevated triglyceride levels tend to increase the risk of heart disease.However, it is still controversial: moderately high triglyceride levels, while not causing cardiovascular disease in and of themselves, can only be associated with other causes. Normal triglyceride levels for men are 40-160 mg / dl and for women 35-135 mg / dl (20). Triglyceride levels above 250 mg / dL should be of concern (20).

Some people speculate that while a vegetarian diet can lower blood cholesterol levels, it may increase triglyceride levels.But as Table 4 shows, 11 studies measuring triglyceride levels in vegans found evidence that vegans have lower triglyceride levels than lacto-ovo vegetarians and non-vegetarians.

90,026

90,014 Totals

Western vegans have an average total cholesterol of 160 mg / dL.This is 40 points lower than the non-vegetarians in the study, and well below the NIHR recommended level of less than 200 mg / dL.

It is, of course, possible to follow a vegan diet high in fat, hydrogenated oils, and low in fiber. In such a case, the benefits of a vegan diet listed above will not be valid. In addition, some people have a genetic predisposition to high cholesterol levels.The College of American Pathologists recommends that adults over 20 have their cholesterol checked every 5 years (18).

Blood pressure

In 2012, a more thorough cross-sectional analysis was published in Adventist Health Research-2. It only studied Caucasians (with white skin) and the results were not adjusted for any factors. The result is shown in Table 5. Vegans had significantly lower blood pressure readings.

90,026

In 2002, the EPIC-Oxford study was published, in which 11,004 subjects took part, it was asked whether they have high blood pressure (22).The results are shown in Table 6.

The result with the low proportion of vegans with high blood pressure was statistically significant.This is the only study to compare the percentage of vegans with high blood pressure to other dietary groups.

Blood pressure was measured in 8663 participants without high blood pressure. The results are shown in Table 7. The results of 4 other studies of blood pressure measurement in vegans since 1980 are also shown in Table 7. Finally, the cumulative result of all 5 studies is also shown in Table 7.

Results show that vegans had lower blood pressure scores than other diet groups.If all participants were included in the EPIC-Oxford study, and not just those with low blood pressure, the difference between vegans and non-vegetarians in Table 7 would be more significant. The difference would also be greater if participants in one study (7) were randomly selected rather than vegans and non-vegetarians with a similar BMI (body mass index).

Meta-Analysis on vegetarians and their blood pressure

In 2014, researchers from Japan published a meta-analysis of clinical trials and a crossover study based on observations of a vegetarian diet and blood pressure (42).Many of the vegetarians studied were actually semi-vegetarians.

According to the results of seven clinical studies, a vegetarian diet reduces the frequency of systolic and diastolic blood pressure by an average of 4.8 and 2.2 mm Hg. Art. respectively. Among 32 cross-sectional studies, vegetarians were found to have lower systolic and diastolic blood pressure by 6.9 and 4.7 mmHg. Art. respectively.

These findings were statistically significant.The authors reported: “According to Welton et al., A 5 mm Hg reduction in systolic blood pressure can result in a 7%, 9% and 14% reduction in all-cause mortality, coronary heart disease and stroke, respectively.”

Why do vegans have lower blood pressure?

Researchers at Epic-Oxford (22) and Adventist Health-2 (40) have suggested that lower body mass index may be, in large part, an explanation for differences in blood pressure between groups.Other factors may include: higher potassium intake, decreased sodium intake, modulation of baroreceptor sensitivity, direct vasodilating effect, changes in catecholamines and renin-angiotensin-aldosterone metabolism, improved glucose tolerance with low insulin levels, and decreased blood viscosity in vegetarians (40) …

Body mass index

Body mass index (BMI) is an indicator measured by dividing weight in kilograms by height in meters, squared (i.e.e., kg / m2). This is a way of measuring weight, taking into account differences in height. A “healthy” BMI is considered to be between 20 and 25. Generally, a BMI of 30 or higher is considered obese (32).

Recent studies have shown that a BMI of 22.5 to 25.0 is associated with a low mortality rate. For some time, it was believed that a low BMI was associated with an increased risk of mortality, but this was mainly due to the relationship with smoking-related diseases.A 2009 meta-analysis of 900,000 people found that even nonsmokers with a BMI below 22.5 have a slight increase in mortality (37). This increase in mortality in people with a BMI below 22.5 has not been explained. The theory behind this suggests that the increase in mortality may be due to lower body fat mass, which is more likely to be lower than lean body mass (although it could also technically include bone or even organ weight) (37, 38) … Current studies on the relationship between BMI and mortality do not separately measure sufficient and insufficient body fat mass.

Adventist Health Report-2 2009

In 2009, cross-sectional data on BMI were presented by the Adventist Health Study-2 (36). Vegans had a lower body mass index than other groups, this finding was statistically significant.

EPIC-Oxford Report 2003

A report from EPIC-Oxford was published in 2003 on BMI levels.The results are shown in Table 9.

Differences between vegans and meat-eaters were mainly attributed to differences in the supply of proteins, polyunsaturated fats and fiber. The authors note that the effect of protein intake on weight is rarely mentioned in the literature, but there are some notes on hormone changes leading to increased abdominal fat. They also note that low fiber intake is pre-associated with higher body weight; the authors believe that when eating fiber, people feel full with fewer calories, it also helps control insulin and reduces fat absorption.

BMI in Western vegans in studies prior to 2003

Table 10 shows the results for 17 studies conducted prior to 2003, excluding the EPIC-Oxford report described above. Results for non-vegetarians in two of these studies (a total of 40 non-vegetarians) were not included in the table, as the researchers specifically selected non-vegetarians who had the same body weight as vegans (7, 25). In addition, a study (13) with 25 vegans was not included because the participants were within 120% of their ideal weight, which would possibly have influenced the average BMI results.

Since the BMIs of many participants were calculated from data obtained from the participants themselves using a questionnaire, and not measured by researchers, the results shown in Table 10 are divided into two groups, respectively.

Based on the results shown in Table 10, it can be seen that vegans have the lowest body mass index in all cases. BMIs for vegans are pretty much the same whether they come from a questionnaire or are measured by researchers. Participants’ BMIs obtained from the questionnaire are the same as in all 17 studies.

The largest study of 2,488 vegans and 32,594 non-vegetarians found a statistically significant difference between the BMI of vegans and non-vegetarians (30, 33).

Due to the fact that all of the above studies were cross-sectional, it is possible that the differences could be explained by the fact that thinner people were more inclined to a vegan diet, rather than a vegan diet made them thinner.

Change in BMI in vegans depending on the duration of the diet

In 1996, a letter to the editor of the British Medical Journal from EPIC-Oxford (31) reported the result of a study of BMI versus time on a diet (less than or more than 5 years of adherence to the diet).The number of participants in each group was as follows:

• 1,652 vegans
• 8,827 lacto-ovo vegetarians;
• 3,776 people who eat fish;
• 6,850 non-vegetarians.

Actual results for BMI were not reported, but data were presented in the graph. The graph showed that vegans who followed the diet for more than 5 years had the lowest body mass index; they were followed in terms of BMI by vegans on a diet less than 5 years old (both men and women).This result is impressive, as most people cannot sustain weight loss for more than one year. Of course, losing weight can be difficult even for vegans, and there are cases of people gaining weight even after switching to a vegan diet. But overall, the result shows that switching to a vegan diet promotes sustained weight loss.

A 2006 EPIC-Oxford report (35) found that over a 5-year study, vegans had the lowest weight gain compared to non-vegetarians, fish-eaters, and lacto-ovo vegetarians.The group of subjects who switched to a diet with less consumption of animal products had the lowest weight gain. The group of subjects who returned to a diet high in animal products had the highest coefficient of weight gain, but this result was not statistically significant. All groups have slightly increased their weight over a 5-year period.

Body fat

What if vegans weigh less simply because they have less muscle mass? Above in Table 10, you can see that vegans have an average BMI of 22.2 to 22.5, which is just in the middle of the healthy range of 20 to 25.Thus, vegans are not too skinny. But what if their weight is low (meaning high fat)?

Table 11 lists studies that measured the percentage of body fat or skinfold thickness (a measure of body fat) in vegans. Determining the percentage of body fat can vary significantly depending on the study method, so averaging the results would be incorrect. Instead, it’s worth assessing the overall trend.Of the 5 studies, vegans had the lowest body fat in all five. The results from these three studies were statistically significant.

So we now know that vegans have a lower BMI and they also tend to have a lower percentage of body fat (although few measurements have been taken).

Homocysteine ​​

Recently, there has been a lot of interest in an indicator of the health level of vegans – the level of homocysteine ​​in the blood. Elevated homocysteine ​​levels are associated with heart disease, stroke, and early death. Numerous studies have shown that non-B12 vegans have high homocysteine ​​levels. For more information, please read the article Mild B12 Deficiency – Elevated Homocysteine ​​and Vitamin B12.Are you getting it?

Output

Overall, the data shows:

• Vegans have lower levels of total cholesterol, LDL cholesterol and triglycerides, and have roughly the same HDL cholesterol levels as lacto-ovo vegetarians and non-vegetarians;
• Vegans have lower blood pressure levels than lacto-ovo vegetarians and non-vegetarians;
• Vegans have a lower body mass index and percentage of fat mass than lacto-ovo vegetarians and non-vegetarians.People who have followed a vegan diet for more than 5 years have the lowest body mass index of any group surveyed.

References

1. Sanders TA, Ellis FR, Dickerson JW. Am J Clin Nutr 1978 May; 31 (5): 805-13.

2. Lock DR, et al. 1982 Sep; 31 (9): 917-21.

3. Roshanai F, Sanders TA. Hum Nutr Appl Nutr. 1984 Oct; 38 (5): 345-54.

4. Kritchevsky D, Tepper SA, Goodman G. Am J Clin Nutr. 1984 Oct; 40 (4 Suppl): 921-6.

5. Fisher M, et al. Arch Intern Med. 1986 Jun; 146 (6): 1193-7.

6. Thorogood M, et al. Britain.Br Med J (Clin Res Ed). 1987 Aug 8; 295 (6594): 351-3.

7. Sanders TA, Key TJ. Hum Nutr Appl Nutr. 1987 Jun; 41 (3): 204-11.

8. Thorogood M, et al. BMJ. 1990 May 19; 300 (6735): 1297-301.

9. Sanders TA, Roshanai F. Eur J Clin Nutr. 1992 Nov; 46 (11): 823-31.

10. Thomas EL, Frost G, Barnard ML, et al.Lipids. 1996 Feb; 31 (2): 145-51.

11. Toohey ML, et al. J Am Coll Nutr. 1998 Oct; 17 (5): 425-34.

12. Li D, et al. Eur J Clin Nutr. 1999 Aug; 53 (8): 612-9.

13. Haddad EH, et al. Am J Clin Nutr. 1999; 70 (suppl): 586S-93S.

14. Krajcovicova-Kudlackova M, et al. Scand J Clin Lab Invest. 2000 Dec; 60 (8): 657-64.

15. Fokkema MR, et al. Prostaglandins Leukot Essent Fatty Acids. 2000 Nov; 63 (5): 287-92.

16.Allen NE, et al. Br J Cancer 2000 Jul; 83 (1): 95-7.

17. Bissoli L, et al. Ann Nutr Metab. 2002; 46 (2): 73-9.

18. CAP. College of American Pathologists. Cholesterol Testing Information. Accessed February 7, 2003.

19. Appleby PN, et al. Am J Clin Nutr. 1999 Sep; 70 (3 Suppl): 525S-531S.

20. LAB. Fischbach F. A Manual of Laboratory & Diagnostic Tests, 6th Ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2000.

21.Sacks FM, Wood PG, Kass EH. Hypertension. 1984 Mar-Apr; 6 (2 Pt 1): 199-201.

22. Appleby PN, Davey GK, Key TJ. Hypertension and blood pressure among meat eaters, fish eaters, vegetarians and vegans in EPIC-Oxford. Public Health Nutr. 2002 Oct; 5 (5): 645-54.

23. Abdulla M, et al. Am J Clin Nutr 1981 Nov; 34 (11): 2464-77.

24. Carlson E, et al. J Plant Foods. 1985; 6: 89-100.

25. Rana SK, Sanders TA. Br J Nutr. 1986 Jul; 56 (1): 17-27.

26. Ross JK, Pusateri DJ, Shultz TD. Am J Clin Nutr. 1990 Mar; 51 (3): 365-70.23.

27. Key TJ, et al. Br J Nutr. 1990 Jul; 64 (1): 111-9.

28. Janelle KC, Barr SI. J Am Diet Assoc. 1995 Feb; 95 (2): 180-6.

29. Herrmann W, et al. Clin Chem. 2001 Jun; 47 (6): 1094-101.

30. Davey GK, et al. Public Health Nutrition. 2003. (In Press)

31. Key T, Davey G. BMJ. 1996 Sep 28; 313 (7060): 816-7.

32.MA. Mahan LK, Escott-Stump S. Krause’s Food, Nutrition, & Diet Therapy, 10th Ed. Philadelphia, PA: W.B. Saunders, Co. 2000.

33. Personal communication with Paul Appleby. February 17, 2003.

34. Spencer EA, Appleby PN, Davey GK, Key TJ. Diet and body mass index in 38000 EPIC-Oxford meat-eaters, fish-eaters, vegetarians and vegans. Int J Obes Relat Metab Disord. 2003 Jun; 27 (6): 728-34.

35. Rosell M, Appleby P, Spencer E, Key T. Weight gain over 5 years in 21,966 meat-eating, fish-eating, vegetarian, and vegan men and women in EPIC-Oxford.Int J Obes (Lond). 2006 Sep; 30 (9): 1389-96. Epub 2006 Mar 14.

36. Tonstad S, Butler T, Yan R, Fraser GE. Type of vegetarian diet, body weight, and prevalence of type 2 diabetes. Diabetes Care. 2009 May; 32 (5): 791-6. Epub 2009 Apr 7.

37. Prospective Studies Collaboration, Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J, Qizilbash N, Collins R, Peto R. Body-mass index and cause-specific mortality in 900,000 adults: collaborative analyzes of 57 prospective studies.Lancet. 2009 Mar 28; 373 (9669): 1083-96.

38. Wandell PE, Carlsson AC, Theobald H. The association between BMI value and long-term mortality. Int J Obes (Lond). 2009 May; 33 (5): 577-82.

39. Fraser GE. Vegetarian diets: what do we know of their effects on common chronic diseases? Am J Clin Nutr. 2009 May; 89 (5): 1607S-1612S. Epub 2009 Mar 25. Review. Erratum in: Am J Clin Nutr. 2009 Jul; 90 (1): 248.

40. Pettersen BJ, Anousheh R, Fan J, Jaceldo-Siegl K, Fraser GE.Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2). Public Health Nutr. 2012 Jan 10: 1-8. [Epub ahead of print]

41. Bradbury KE, Crowe FL, Appleby PN, Schmidt JA, Travis RC, Key TJ. Serum concentrations of cholesterol, apolipoprotein A-I and apolipoprotein B in a total of 1694 meat-eaters, fish-eaters, vegetarians and vegans. Eur J Clin Nutr. 2013 Dec 18. [Epub ahead of print]

42. Yokoyama Y, Nishimura K, Barnard ND, Takegami M, Watanabe M, Sekikawa A, Okamura T, Miyamoto Y.Vegetarian Diets and Blood Pressure: A Meta-analysis. JAMA Intern Med. 2014 Feb 24.

90,000 Cholesterol and Lipid Profile | Blood pressure

Contents

Executive Summary

There have been many studies with vegans measuring cholesterol, blood pressure, body weight, and other markers of various diseases. Most of these studies also looked at lacto-ovo vegetarians, fish eaters, and non-vegetarians.This article includes research dating back to 1980, as there has been little previous research involving vegans.

Lipid profile

Lipids are fat-soluble substances, including cholesterol and fatty acids. Blood lipid profile measurement mainly includes total cholesterol, LDL cholesterol (low density lipoprotein cholesterol), HDL cholesterol (high density lipoprotein cholesterol) and triglycerides.

Total cholesterol is an indicator for all types of blood cholesterol.Cholesterol is divided into types depending on the lipoproteins that carry it in the blood. Low-density lipoprotein (LDL) cholesterol is considered “bad” because it tends to accumulate on the walls of arteries, causing heart disease. High-density lipoprotein (HDL) cholesterol is considered “good” because it is carried away from the tissues for processing in the liver, where it is then broken down or excreted through the gastrointestinal tract as bile. Fiber (mostly soluble) can bind to cholesterol and excrete it through the stool.

There are also other lipoproteins such as very low density lipoproteins (VLDL). They are not covered in this article as they have not been studied extensively with vegans.

Cholesterol in the EPIC-Oxford study

The most recent EPIC-Oxford study on cholesterol compares vegetarians and non-vegetarians with a healthy lifestyle (41). The results are presented in Table 1 and show that vegans had rates 34 mg / dL and 23 mg / dL lower than non-vegetarians, men and women, respectively.The biggest differences were for non-HDL cholesterol. Adjusting the results for body mass index reduced the difference to 13% for men and 17% for women.

Vegans also had significantly lower levels of apolipoprotein B, which is believed to cause the buildup of fatty deposits in the arteries.

The study authors suggest that vegans had lower cholesterol levels due to lower body mass index, higher intake of polyunsaturated fat instead of saturated fat, and higher fiber intake.

Cholesterol in Western Vegans (1980 – 2002)

Between 1980 and 2002, 17 studies were conducted on cholesterol levels in Western vegans. The median cholesterol level for vegans was 160 mg / dL compared to 202 mg / dL for non-vegetarians. Table 2 shows the results of the study.

Cholesterol in US Vegans

Of the 17 studies shown in Table 2, 5 were with US vegans.Of these studies, the lowest average cholesterol was 135 mg / dL. The data from these 5 studies are detailed in Table 3. The mean total cholesterol level in 135 vegans was 146 mg / dL.

Triglycerides

Elevated triglyceride levels tend to increase the risk of heart disease.However, it is still controversial: moderately high triglyceride levels, while not causing cardiovascular disease in and of themselves, can only be associated with other causes. Normal triglyceride levels for men are 40-160 mg / dl and for women 35-135 mg / dl (20). Triglyceride levels above 250 mg / dL should be of concern (20).

Some people speculate that while a vegetarian diet can lower blood cholesterol levels, it may increase triglyceride levels.But as Table 4 shows, 11 studies measuring triglyceride levels in vegans found evidence that vegans have lower triglyceride levels than lacto-ovo vegetarians and non-vegetarians.

90,026

90,014 Totals

Western vegans have an average total cholesterol of 160 mg / dL.This is 40 points lower than the non-vegetarians in the study, and well below the NIHR recommended level of less than 200 mg / dL.

It is, of course, possible to follow a vegan diet high in fat, hydrogenated oils, and low in fiber. In such a case, the benefits of a vegan diet listed above will not be valid. In addition, some people have a genetic predisposition to high cholesterol levels.The College of American Pathologists recommends that adults over 20 have their cholesterol checked every 5 years (18).

Blood pressure

In 2012, a more thorough cross-sectional analysis was published in Adventist Health Research-2. It only studied Caucasians (with white skin) and the results were not adjusted for any factors. The result is shown in Table 5. Vegans had significantly lower blood pressure readings.

90,026

In 2002, the EPIC-Oxford study was published, in which 11,004 subjects took part, it was asked whether they have high blood pressure (22).The results are shown in Table 6.

The result with the low proportion of vegans with high blood pressure was statistically significant.This is the only study to compare the percentage of vegans with high blood pressure to other dietary groups.

Blood pressure was measured in 8663 participants without high blood pressure. The results are shown in Table 7. The results of 4 other studies of blood pressure measurement in vegans since 1980 are also shown in Table 7. Finally, the cumulative result of all 5 studies is also shown in Table 7.

Results show that vegans had lower blood pressure scores than other diet groups.If all participants were included in the EPIC-Oxford study, and not just those with low blood pressure, the difference between vegans and non-vegetarians in Table 7 would be more significant. The difference would also be greater if participants in one study (7) were randomly selected rather than vegans and non-vegetarians with a similar BMI (body mass index).

Meta-Analysis on vegetarians and their blood pressure

In 2014, researchers from Japan published a meta-analysis of clinical trials and a crossover study based on observations of a vegetarian diet and blood pressure (42).Many of the vegetarians studied were actually semi-vegetarians.

According to the results of seven clinical studies, a vegetarian diet reduces the frequency of systolic and diastolic blood pressure by an average of 4.8 and 2.2 mm Hg. Art. respectively. Among 32 cross-sectional studies, vegetarians were found to have lower systolic and diastolic blood pressure by 6.9 and 4.7 mmHg. Art. respectively.

These findings were statistically significant.The authors reported: “According to Welton et al., A 5 mm Hg reduction in systolic blood pressure can result in a 7%, 9% and 14% reduction in all-cause mortality, coronary heart disease and stroke, respectively.”

Why do vegans have lower blood pressure?

Researchers at Epic-Oxford (22) and Adventist Health-2 (40) have suggested that lower body mass index may be, in large part, an explanation for differences in blood pressure between groups.Other factors may include: higher potassium intake, decreased sodium intake, modulation of baroreceptor sensitivity, direct vasodilating effect, changes in catecholamines and renin-angiotensin-aldosterone metabolism, improved glucose tolerance with low insulin levels, and decreased blood viscosity in vegetarians (40) …

Body mass index

Body mass index (BMI) is an indicator measured by dividing weight in kilograms by height in meters, squared (i.e.e., kg / m2). This is a way of measuring weight, taking into account differences in height. A “healthy” BMI is considered to be between 20 and 25. Generally, a BMI of 30 or higher is considered obese (32).

Recent studies have shown that a BMI of 22.5 to 25.0 is associated with a low mortality rate. For some time, it was believed that a low BMI was associated with an increased risk of mortality, but this was mainly due to the relationship with smoking-related diseases.A 2009 meta-analysis of 900,000 people found that even nonsmokers with a BMI below 22.5 have a slight increase in mortality (37). This increase in mortality in people with a BMI below 22.5 has not been explained. The theory behind this suggests that the increase in mortality may be due to lower body fat mass, which is more likely to be lower than lean body mass (although it could also technically include bone or even organ weight) (37, 38) … Current studies on the relationship between BMI and mortality do not separately measure sufficient and insufficient body fat mass.

Adventist Health Report-2 2009

In 2009, cross-sectional data on BMI were presented by the Adventist Health Study-2 (36). Vegans had a lower body mass index than other groups, this finding was statistically significant.

EPIC-Oxford Report 2003

A report from EPIC-Oxford was published in 2003 on BMI levels.The results are shown in Table 9.

Differences between vegans and meat-eaters were mainly attributed to differences in the supply of proteins, polyunsaturated fats and fiber. The authors note that the effect of protein intake on weight is rarely mentioned in the literature, but there are some notes on hormone changes leading to increased abdominal fat. They also note that low fiber intake is pre-associated with higher body weight; the authors believe that when eating fiber, people feel full with fewer calories, it also helps control insulin and reduces fat absorption.

BMI in Western vegans in studies prior to 2003

Table 10 shows the results for 17 studies conducted prior to 2003, excluding the EPIC-Oxford report described above. Results for non-vegetarians in two of these studies (a total of 40 non-vegetarians) were not included in the table, as the researchers specifically selected non-vegetarians who had the same body weight as vegans (7, 25). In addition, a study (13) with 25 vegans was not included because the participants were within 120% of their ideal weight, which would possibly have influenced the average BMI results.

Since the BMIs of many participants were calculated from data obtained from the participants themselves using a questionnaire, and not measured by researchers, the results shown in Table 10 are divided into two groups, respectively.

Based on the results shown in Table 10, it can be seen that vegans have the lowest body mass index in all cases. BMIs for vegans are pretty much the same whether they come from a questionnaire or are measured by researchers. Participants’ BMIs obtained from the questionnaire are the same as in all 17 studies.

The largest study of 2,488 vegans and 32,594 non-vegetarians found a statistically significant difference between the BMI of vegans and non-vegetarians (30, 33).

Due to the fact that all of the above studies were cross-sectional, it is possible that the differences could be explained by the fact that thinner people were more inclined to a vegan diet, rather than a vegan diet made them thinner.

Change in BMI in vegans depending on the duration of the diet

In 1996, a letter to the editor of the British Medical Journal from EPIC-Oxford (31) reported the result of a study of BMI versus time on a diet (less than or more than 5 years of adherence to the diet).The number of participants in each group was as follows:

• 1,652 vegans
• 8,827 lacto-ovo vegetarians;
• 3,776 people who eat fish;
• 6,850 non-vegetarians.

Actual results for BMI were not reported, but data were presented in the graph. The graph showed that vegans who followed the diet for more than 5 years had the lowest body mass index; they were followed in terms of BMI by vegans on a diet less than 5 years old (both men and women).This result is impressive, as most people cannot sustain weight loss for more than one year. Of course, losing weight can be difficult even for vegans, and there are cases of people gaining weight even after switching to a vegan diet. But overall, the result shows that switching to a vegan diet promotes sustained weight loss.

A 2006 EPIC-Oxford report (35) found that over a 5-year study, vegans had the lowest weight gain compared to non-vegetarians, fish-eaters, and lacto-ovo vegetarians.The group of subjects who switched to a diet with less consumption of animal products had the lowest weight gain. The group of subjects who returned to a diet high in animal products had the highest coefficient of weight gain, but this result was not statistically significant. All groups have slightly increased their weight over a 5-year period.

Body fat

What if vegans weigh less simply because they have less muscle mass? Above in Table 10, you can see that vegans have an average BMI of 22.2 to 22.5, which is just in the middle of the healthy range of 20 to 25.Thus, vegans are not too skinny. But what if their weight is low (meaning high fat)?

Table 11 lists studies that measured the percentage of body fat or skinfold thickness (a measure of body fat) in vegans. Determining the percentage of body fat can vary significantly depending on the study method, so averaging the results would be incorrect. Instead, it’s worth assessing the overall trend.Of the 5 studies, vegans had the lowest body fat in all five. The results from these three studies were statistically significant.

So we now know that vegans have a lower BMI and they also tend to have a lower percentage of body fat (although few measurements have been taken).

Homocysteine ​​

Recently, there has been a lot of interest in an indicator of the health level of vegans – the level of homocysteine ​​in the blood. Elevated homocysteine ​​levels are associated with heart disease, stroke, and early death. Numerous studies have shown that non-B12 vegans have high homocysteine ​​levels. For more information, please read the article Mild B12 Deficiency – Elevated Homocysteine ​​and Vitamin B12.Are you getting it?

Output

Overall, the data shows:

• Vegans have lower levels of total cholesterol, LDL cholesterol and triglycerides, and have roughly the same HDL cholesterol levels as lacto-ovo vegetarians and non-vegetarians;
• Vegans have lower blood pressure levels than lacto-ovo vegetarians and non-vegetarians;
• Vegans have a lower body mass index and percentage of fat mass than lacto-ovo vegetarians and non-vegetarians.People who have followed a vegan diet for more than 5 years have the lowest body mass index of any group surveyed.

References

1. Sanders TA, Ellis FR, Dickerson JW. Am J Clin Nutr 1978 May; 31 (5): 805-13.

2. Lock DR, et al. 1982 Sep; 31 (9): 917-21.

3. Roshanai F, Sanders TA. Hum Nutr Appl Nutr. 1984 Oct; 38 (5): 345-54.

4. Kritchevsky D, Tepper SA, Goodman G. Am J Clin Nutr. 1984 Oct; 40 (4 Suppl): 921-6.

5. Fisher M, et al. Arch Intern Med. 1986 Jun; 146 (6): 1193-7.

6. Thorogood M, et al. Britain.Br Med J (Clin Res Ed). 1987 Aug 8; 295 (6594): 351-3.

7. Sanders TA, Key TJ. Hum Nutr Appl Nutr. 1987 Jun; 41 (3): 204-11.

8. Thorogood M, et al. BMJ. 1990 May 19; 300 (6735): 1297-301.

9. Sanders TA, Roshanai F. Eur J Clin Nutr. 1992 Nov; 46 (11): 823-31.

10. Thomas EL, Frost G, Barnard ML, et al.Lipids. 1996 Feb; 31 (2): 145-51.

11. Toohey ML, et al. J Am Coll Nutr. 1998 Oct; 17 (5): 425-34.

12. Li D, et al. Eur J Clin Nutr. 1999 Aug; 53 (8): 612-9.

13. Haddad EH, et al. Am J Clin Nutr. 1999; 70 (suppl): 586S-93S.

14. Krajcovicova-Kudlackova M, et al. Scand J Clin Lab Invest. 2000 Dec; 60 (8): 657-64.

15. Fokkema MR, et al. Prostaglandins Leukot Essent Fatty Acids. 2000 Nov; 63 (5): 287-92.

16.Allen NE, et al. Br J Cancer 2000 Jul; 83 (1): 95-7.

17. Bissoli L, et al. Ann Nutr Metab. 2002; 46 (2): 73-9.

18. CAP. College of American Pathologists. Cholesterol Testing Information. Accessed February 7, 2003.

19. Appleby PN, et al. Am J Clin Nutr. 1999 Sep; 70 (3 Suppl): 525S-531S.

20. LAB. Fischbach F. A Manual of Laboratory & Diagnostic Tests, 6th Ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2000.

21.Sacks FM, Wood PG, Kass EH. Hypertension. 1984 Mar-Apr; 6 (2 Pt 1): 199-201.

22. Appleby PN, Davey GK, Key TJ. Hypertension and blood pressure among meat eaters, fish eaters, vegetarians and vegans in EPIC-Oxford. Public Health Nutr. 2002 Oct; 5 (5): 645-54.

23. Abdulla M, et al. Am J Clin Nutr 1981 Nov; 34 (11): 2464-77.

24. Carlson E, et al. J Plant Foods. 1985; 6: 89-100.

25. Rana SK, Sanders TA. Br J Nutr. 1986 Jul; 56 (1): 17-27.

26. Ross JK, Pusateri DJ, Shultz TD. Am J Clin Nutr. 1990 Mar; 51 (3): 365-70.23.

27. Key TJ, et al. Br J Nutr. 1990 Jul; 64 (1): 111-9.

28. Janelle KC, Barr SI. J Am Diet Assoc. 1995 Feb; 95 (2): 180-6.

29. Herrmann W, et al. Clin Chem. 2001 Jun; 47 (6): 1094-101.

30. Davey GK, et al. Public Health Nutrition. 2003. (In Press)

31. Key T, Davey G. BMJ. 1996 Sep 28; 313 (7060): 816-7.

32.MA. Mahan LK, Escott-Stump S. Krause’s Food, Nutrition, & Diet Therapy, 10th Ed. Philadelphia, PA: W.B. Saunders, Co. 2000.

33. Personal communication with Paul Appleby. February 17, 2003.

34. Spencer EA, Appleby PN, Davey GK, Key TJ. Diet and body mass index in 38000 EPIC-Oxford meat-eaters, fish-eaters, vegetarians and vegans. Int J Obes Relat Metab Disord. 2003 Jun; 27 (6): 728-34.

35. Rosell M, Appleby P, Spencer E, Key T. Weight gain over 5 years in 21,966 meat-eating, fish-eating, vegetarian, and vegan men and women in EPIC-Oxford.Int J Obes (Lond). 2006 Sep; 30 (9): 1389-96. Epub 2006 Mar 14.

36. Tonstad S, Butler T, Yan R, Fraser GE. Type of vegetarian diet, body weight, and prevalence of type 2 diabetes. Diabetes Care. 2009 May; 32 (5): 791-6. Epub 2009 Apr 7.

37. Prospective Studies Collaboration, Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J, Qizilbash N, Collins R, Peto R. Body-mass index and cause-specific mortality in 900,000 adults: collaborative analyzes of 57 prospective studies.Lancet. 2009 Mar 28; 373 (9669): 1083-96.

38. Wandell PE, Carlsson AC, Theobald H. The association between BMI value and long-term mortality. Int J Obes (Lond). 2009 May; 33 (5): 577-82.

39. Fraser GE. Vegetarian diets: what do we know of their effects on common chronic diseases? Am J Clin Nutr. 2009 May; 89 (5): 1607S-1612S. Epub 2009 Mar 25. Review. Erratum in: Am J Clin Nutr. 2009 Jul; 90 (1): 248.

40. Pettersen BJ, Anousheh R, Fan J, Jaceldo-Siegl K, Fraser GE.Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2). Public Health Nutr. 2012 Jan 10: 1-8. [Epub ahead of print]

41. Bradbury KE, Crowe FL, Appleby PN, Schmidt JA, Travis RC, Key TJ. Serum concentrations of cholesterol, apolipoprotein A-I and apolipoprotein B in a total of 1694 meat-eaters, fish-eaters, vegetarians and vegans. Eur J Clin Nutr. 2013 Dec 18. [Epub ahead of print]

42. Yokoyama Y, Nishimura K, Barnard ND, Takegami M, Watanabe M, Sekikawa A, Okamura T, Miyamoto Y.Vegetarian Diets and Blood Pressure: A Meta-analysis. JAMA Intern Med. 2014 Feb 24.

90,000 Cholesterol and Lipid Profile | Blood pressure

Contents

Executive Summary

There have been many studies with vegans measuring cholesterol, blood pressure, body weight, and other markers of various diseases. Most of these studies also looked at lacto-ovo vegetarians, fish eaters, and non-vegetarians.This article includes research dating back to 1980, as there has been little previous research involving vegans.

Lipid profile

Lipids are fat-soluble substances, including cholesterol and fatty acids. Blood lipid profile measurement mainly includes total cholesterol, LDL cholesterol (low density lipoprotein cholesterol), HDL cholesterol (high density lipoprotein cholesterol) and triglycerides.

Total cholesterol is an indicator for all types of blood cholesterol.Cholesterol is divided into types depending on the lipoproteins that carry it in the blood. Low-density lipoprotein (LDL) cholesterol is considered “bad” because it tends to accumulate on the walls of arteries, causing heart disease. High-density lipoprotein (HDL) cholesterol is considered “good” because it is carried away from the tissues for processing in the liver, where it is then broken down or excreted through the gastrointestinal tract as bile. Fiber (mostly soluble) can bind to cholesterol and excrete it through the stool.

There are also other lipoproteins such as very low density lipoproteins (VLDL). They are not covered in this article as they have not been studied extensively with vegans.

Cholesterol in the EPIC-Oxford study

The most recent EPIC-Oxford study on cholesterol compares vegetarians and non-vegetarians with a healthy lifestyle (41). The results are presented in Table 1 and show that vegans had rates 34 mg / dL and 23 mg / dL lower than non-vegetarians, men and women, respectively.The biggest differences were for non-HDL cholesterol. Adjusting the results for body mass index reduced the difference to 13% for men and 17% for women.

Vegans also had significantly lower levels of apolipoprotein B, which is believed to cause the buildup of fatty deposits in the arteries.

The study authors suggest that vegans had lower cholesterol levels due to lower body mass index, higher intake of polyunsaturated fat instead of saturated fat, and higher fiber intake.

Cholesterol in Western Vegans (1980 – 2002)

Between 1980 and 2002, 17 studies were conducted on cholesterol levels in Western vegans. The median cholesterol level for vegans was 160 mg / dL compared to 202 mg / dL for non-vegetarians. Table 2 shows the results of the study.

Cholesterol in US Vegans

Of the 17 studies shown in Table 2, 5 were with US vegans.Of these studies, the lowest average cholesterol was 135 mg / dL. The data from these 5 studies are detailed in Table 3. The mean total cholesterol level in 135 vegans was 146 mg / dL.

Triglycerides

Elevated triglyceride levels tend to increase the risk of heart disease.However, it is still controversial: moderately high triglyceride levels, while not causing cardiovascular disease in and of themselves, can only be associated with other causes. Normal triglyceride levels for men are 40-160 mg / dl and for women 35-135 mg / dl (20). Triglyceride levels above 250 mg / dL should be of concern (20).

Some people speculate that while a vegetarian diet can lower blood cholesterol levels, it may increase triglyceride levels.But as Table 4 shows, 11 studies measuring triglyceride levels in vegans found evidence that vegans have lower triglyceride levels than lacto-ovo vegetarians and non-vegetarians.

90,026

90,014 Totals

Western vegans have an average total cholesterol of 160 mg / dL.This is 40 points lower than the non-vegetarians in the study, and well below the NIHR recommended level of less than 200 mg / dL.

It is, of course, possible to follow a vegan diet high in fat, hydrogenated oils, and low in fiber. In such a case, the benefits of a vegan diet listed above will not be valid. In addition, some people have a genetic predisposition to high cholesterol levels.The College of American Pathologists recommends that adults over 20 have their cholesterol checked every 5 years (18).

Blood pressure

In 2012, a more thorough cross-sectional analysis was published in Adventist Health Research-2. It only studied Caucasians (with white skin) and the results were not adjusted for any factors. The result is shown in Table 5. Vegans had significantly lower blood pressure readings.

90,026

In 2002, the EPIC-Oxford study was published, in which 11,004 subjects took part, it was asked whether they have high blood pressure (22).The results are shown in Table 6.

The result with the low proportion of vegans with high blood pressure was statistically significant.This is the only study to compare the percentage of vegans with high blood pressure to other dietary groups.

Blood pressure was measured in 8663 participants without high blood pressure. The results are shown in Table 7. The results of 4 other studies of blood pressure measurement in vegans since 1980 are also shown in Table 7. Finally, the cumulative result of all 5 studies is also shown in Table 7.

Results show that vegans had lower blood pressure scores than other diet groups.If all participants were included in the EPIC-Oxford study, and not just those with low blood pressure, the difference between vegans and non-vegetarians in Table 7 would be more significant. The difference would also be greater if participants in one study (7) were randomly selected rather than vegans and non-vegetarians with a similar BMI (body mass index).

Meta-Analysis on vegetarians and their blood pressure

In 2014, researchers from Japan published a meta-analysis of clinical trials and a crossover study based on observations of a vegetarian diet and blood pressure (42).Many of the vegetarians studied were actually semi-vegetarians.

According to the results of seven clinical studies, a vegetarian diet reduces the frequency of systolic and diastolic blood pressure by an average of 4.8 and 2.2 mm Hg. Art. respectively. Among 32 cross-sectional studies, vegetarians were found to have lower systolic and diastolic blood pressure by 6.9 and 4.7 mmHg. Art. respectively.

These findings were statistically significant.The authors reported: “According to Welton et al., A 5 mm Hg reduction in systolic blood pressure can result in a 7%, 9% and 14% reduction in all-cause mortality, coronary heart disease and stroke, respectively.”

Why do vegans have lower blood pressure?

Researchers at Epic-Oxford (22) and Adventist Health-2 (40) have suggested that lower body mass index may be, in large part, an explanation for differences in blood pressure between groups.Other factors may include: higher potassium intake, decreased sodium intake, modulation of baroreceptor sensitivity, direct vasodilating effect, changes in catecholamines and renin-angiotensin-aldosterone metabolism, improved glucose tolerance with low insulin levels, and decreased blood viscosity in vegetarians (40) …

Body mass index

Body mass index (BMI) is an indicator measured by dividing weight in kilograms by height in meters, squared (i.e.e., kg / m2). This is a way of measuring weight, taking into account differences in height. A “healthy” BMI is considered to be between 20 and 25. Generally, a BMI of 30 or higher is considered obese (32).

Recent studies have shown that a BMI of 22.5 to 25.0 is associated with a low mortality rate. For some time, it was believed that a low BMI was associated with an increased risk of mortality, but this was mainly due to the relationship with smoking-related diseases.A 2009 meta-analysis of 900,000 people found that even nonsmokers with a BMI below 22.5 have a slight increase in mortality (37). This increase in mortality in people with a BMI below 22.5 has not been explained. The theory behind this suggests that the increase in mortality may be due to lower body fat mass, which is more likely to be lower than lean body mass (although it could also technically include bone or even organ weight) (37, 38) … Current studies on the relationship between BMI and mortality do not separately measure sufficient and insufficient body fat mass.

Adventist Health Report-2 2009

In 2009, cross-sectional data on BMI were presented by the Adventist Health Study-2 (36). Vegans had a lower body mass index than other groups, this finding was statistically significant.

EPIC-Oxford Report 2003

A report from EPIC-Oxford was published in 2003 on BMI levels.The results are shown in Table 9.

Differences between vegans and meat-eaters were mainly attributed to differences in the supply of proteins, polyunsaturated fats and fiber. The authors note that the effect of protein intake on weight is rarely mentioned in the literature, but there are some notes on hormone changes leading to increased abdominal fat. They also note that low fiber intake is pre-associated with higher body weight; the authors believe that when eating fiber, people feel full with fewer calories, it also helps control insulin and reduces fat absorption.

BMI in Western vegans in studies prior to 2003

Table 10 shows the results for 17 studies conducted prior to 2003, excluding the EPIC-Oxford report described above. Results for non-vegetarians in two of these studies (a total of 40 non-vegetarians) were not included in the table, as the researchers specifically selected non-vegetarians who had the same body weight as vegans (7, 25). In addition, a study (13) with 25 vegans was not included because the participants were within 120% of their ideal weight, which would possibly have influenced the average BMI results.

Since the BMIs of many participants were calculated from data obtained from the participants themselves using a questionnaire, and not measured by researchers, the results shown in Table 10 are divided into two groups, respectively.

Based on the results shown in Table 10, it can be seen that vegans have the lowest body mass index in all cases. BMIs for vegans are pretty much the same whether they come from a questionnaire or are measured by researchers. Participants’ BMIs obtained from the questionnaire are the same as in all 17 studies.

The largest study of 2,488 vegans and 32,594 non-vegetarians found a statistically significant difference between the BMI of vegans and non-vegetarians (30, 33).

Due to the fact that all of the above studies were cross-sectional, it is possible that the differences could be explained by the fact that thinner people were more inclined to a vegan diet, rather than a vegan diet made them thinner.

Change in BMI in vegans depending on the duration of the diet

In 1996, a letter to the editor of the British Medical Journal from EPIC-Oxford (31) reported the result of a study of BMI versus time on a diet (less than or more than 5 years of adherence to the diet).The number of participants in each group was as follows:

• 1,652 vegans
• 8,827 lacto-ovo vegetarians;
• 3,776 people who eat fish;
• 6,850 non-vegetarians.

Actual results for BMI were not reported, but data were presented in the graph. The graph showed that vegans who followed the diet for more than 5 years had the lowest body mass index; they were followed in terms of BMI by vegans on a diet less than 5 years old (both men and women).This result is impressive, as most people cannot sustain weight loss for more than one year. Of course, losing weight can be difficult even for vegans, and there are cases of people gaining weight even after switching to a vegan diet. But overall, the result shows that switching to a vegan diet promotes sustained weight loss.

A 2006 EPIC-Oxford report (35) found that over a 5-year study, vegans had the lowest weight gain compared to non-vegetarians, fish-eaters, and lacto-ovo vegetarians.The group of subjects who switched to a diet with less consumption of animal products had the lowest weight gain. The group of subjects who returned to a diet high in animal products had the highest coefficient of weight gain, but this result was not statistically significant. All groups have slightly increased their weight over a 5-year period.

Body fat

What if vegans weigh less simply because they have less muscle mass? Above in Table 10, you can see that vegans have an average BMI of 22.2 to 22.5, which is just in the middle of the healthy range of 20 to 25.Thus, vegans are not too skinny. But what if their weight is low (meaning high fat)?

Table 11 lists studies that measured the percentage of body fat or skinfold thickness (a measure of body fat) in vegans. Determining the percentage of body fat can vary significantly depending on the study method, so averaging the results would be incorrect. Instead, it’s worth assessing the overall trend.Of the 5 studies, vegans had the lowest body fat in all five. The results from these three studies were statistically significant.

So we now know that vegans have a lower BMI and they also tend to have a lower percentage of body fat (although few measurements have been taken).

Homocysteine ​​

Recently, there has been a lot of interest in an indicator of the health level of vegans – the level of homocysteine ​​in the blood. Elevated homocysteine ​​levels are associated with heart disease, stroke, and early death. Numerous studies have shown that non-B12 vegans have high homocysteine ​​levels. For more information, please read the article Mild B12 Deficiency – Elevated Homocysteine ​​and Vitamin B12.Are you getting it?

Output

Overall, the data shows:

• Vegans have lower levels of total cholesterol, LDL cholesterol and triglycerides, and have roughly the same HDL cholesterol levels as lacto-ovo vegetarians and non-vegetarians;
• Vegans have lower blood pressure levels than lacto-ovo vegetarians and non-vegetarians;
• Vegans have a lower body mass index and percentage of fat mass than lacto-ovo vegetarians and non-vegetarians.People who have followed a vegan diet for more than 5 years have the lowest body mass index of any group surveyed.

References

1. Sanders TA, Ellis FR, Dickerson JW. Am J Clin Nutr 1978 May; 31 (5): 805-13.

2. Lock DR, et al. 1982 Sep; 31 (9): 917-21.

3. Roshanai F, Sanders TA. Hum Nutr Appl Nutr. 1984 Oct; 38 (5): 345-54.

4. Kritchevsky D, Tepper SA, Goodman G. Am J Clin Nutr. 1984 Oct; 40 (4 Suppl): 921-6.

5. Fisher M, et al. Arch Intern Med. 1986 Jun; 146 (6): 1193-7.

6. Thorogood M, et al. Britain.Br Med J (Clin Res Ed). 1987 Aug 8; 295 (6594): 351-3.

7. Sanders TA, Key TJ. Hum Nutr Appl Nutr. 1987 Jun; 41 (3): 204-11.

8. Thorogood M, et al. BMJ. 1990 May 19; 300 (6735): 1297-301.

9. Sanders TA, Roshanai F. Eur J Clin Nutr. 1992 Nov; 46 (11): 823-31.

10. Thomas EL, Frost G, Barnard ML, et al.Lipids. 1996 Feb; 31 (2): 145-51.

11. Toohey ML, et al. J Am Coll Nutr. 1998 Oct; 17 (5): 425-34.

12. Li D, et al. Eur J Clin Nutr. 1999 Aug; 53 (8): 612-9.

13. Haddad EH, et al. Am J Clin Nutr. 1999; 70 (suppl): 586S-93S.

14. Krajcovicova-Kudlackova M, et al. Scand J Clin Lab Invest. 2000 Dec; 60 (8): 657-64.

15. Fokkema MR, et al. Prostaglandins Leukot Essent Fatty Acids. 2000 Nov; 63 (5): 287-92.

16.Allen NE, et al. Br J Cancer 2000 Jul; 83 (1): 95-7.

17. Bissoli L, et al. Ann Nutr Metab. 2002; 46 (2): 73-9.

18. CAP. College of American Pathologists. Cholesterol Testing Information. Accessed February 7, 2003.

19. Appleby PN, et al. Am J Clin Nutr. 1999 Sep; 70 (3 Suppl): 525S-531S.

20. LAB. Fischbach F. A Manual of Laboratory & Diagnostic Tests, 6th Ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2000.

21.Sacks FM, Wood PG, Kass EH. Hypertension. 1984 Mar-Apr; 6 (2 Pt 1): 199-201.

22. Appleby PN, Davey GK, Key TJ. Hypertension and blood pressure among meat eaters, fish eaters, vegetarians and vegans in EPIC-Oxford. Public Health Nutr. 2002 Oct; 5 (5): 645-54.

23. Abdulla M, et al. Am J Clin Nutr 1981 Nov; 34 (11): 2464-77.

24. Carlson E, et al. J Plant Foods. 1985; 6: 89-100.

25. Rana SK, Sanders TA. Br J Nutr. 1986 Jul; 56 (1): 17-27.

26. Ross JK, Pusateri DJ, Shultz TD. Am J Clin Nutr. 1990 Mar; 51 (3): 365-70.23.

27. Key TJ, et al. Br J Nutr. 1990 Jul; 64 (1): 111-9.

28. Janelle KC, Barr SI. J Am Diet Assoc. 1995 Feb; 95 (2): 180-6.

29. Herrmann W, et al. Clin Chem. 2001 Jun; 47 (6): 1094-101.

30. Davey GK, et al. Public Health Nutrition. 2003. (In Press)

31. Key T, Davey G. BMJ. 1996 Sep 28; 313 (7060): 816-7.

32.MA. Mahan LK, Escott-Stump S. Krause’s Food, Nutrition, & Diet Therapy, 10th Ed. Philadelphia, PA: W.B. Saunders, Co. 2000.

33. Personal communication with Paul Appleby. February 17, 2003.

34. Spencer EA, Appleby PN, Davey GK, Key TJ. Diet and body mass index in 38000 EPIC-Oxford meat-eaters, fish-eaters, vegetarians and vegans. Int J Obes Relat Metab Disord. 2003 Jun; 27 (6): 728-34.

35. Rosell M, Appleby P, Spencer E, Key T. Weight gain over 5 years in 21,966 meat-eating, fish-eating, vegetarian, and vegan men and women in EPIC-Oxford.Int J Obes (Lond). 2006 Sep; 30 (9): 1389-96. Epub 2006 Mar 14.

36. Tonstad S, Butler T, Yan R, Fraser GE. Type of vegetarian diet, body weight, and prevalence of type 2 diabetes. Diabetes Care. 2009 May; 32 (5): 791-6. Epub 2009 Apr 7.

37. Prospective Studies Collaboration, Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J, Qizilbash N, Collins R, Peto R. Body-mass index and cause-specific mortality in 900,000 adults: collaborative analyzes of 57 prospective studies.Lancet. 2009 Mar 28; 373 (9669): 1083-96.

38. Wandell PE, Carlsson AC, Theobald H. The association between BMI value and long-term mortality. Int J Obes (Lond). 2009 May; 33 (5): 577-82.

39. Fraser GE. Vegetarian diets: what do we know of their effects on common chronic diseases? Am J Clin Nutr. 2009 May; 89 (5): 1607S-1612S. Epub 2009 Mar 25. Review. Erratum in: Am J Clin Nutr. 2009 Jul; 90 (1): 248.

40. Pettersen BJ, Anousheh R, Fan J, Jaceldo-Siegl K, Fraser GE.Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2). Public Health Nutr. 2012 Jan 10: 1-8. [Epub ahead of print]

41. Bradbury KE, Crowe FL, Appleby PN, Schmidt JA, Travis RC, Key TJ. Serum concentrations of cholesterol, apolipoprotein A-I and apolipoprotein B in a total of 1694 meat-eaters, fish-eaters, vegetarians and vegans. Eur J Clin Nutr. 2013 Dec 18. [Epub ahead of print]

42. Yokoyama Y, Nishimura K, Barnard ND, Takegami M, Watanabe M, Sekikawa A, Okamura T, Miyamoto Y.Vegetarian Diets and Blood Pressure: A Meta-analysis. JAMA Intern Med. 2014 Feb 24.

90,000 Cholesterol. A source of evil or a vital substance?

“Partner” No. 7 (202) 2014

Answering readers’ questions

Dr. Olga Grishchenko (Heppenheim)

Everyone knows about cholesterol today.Many of us are convinced that the very concept of “cholesterol” and everything associated with it, carries with it a negative. In fact, this is not at all the case. Cholesterol is an important building material for the cells and tissues of the body, which is vital for humans. It is a part of the membranes (membranes) of all cells of the body, there is a lot of it in the nervous tissue, many are formed from cholesterol, in particular sex hormones. Cholesterol is a vital substance produced in the liver and also taken by us with food.About 80% of cholesterol is produced by the body itself, the remaining 20% ​​comes from food.

Cholesterol values ​​

The optimal cholesterol content in an adult is below 200 mg / dl. The upper limit of the norm is 240 mg / dl; a level over 240 mg / dl is considered high. The higher the level of cholesterol in the body, the higher the risk of developing cardiovascular disease. Cholesterol levels rise when eating foods rich in fats, as well as when taking certain medications, pregnancy, hereditary diseases, and insufficient thyroid function.Sometimes cholesterol levels are below normal (less than 100 mg / dl), which can be observed in cancer, dystrophy, liver disease, hyperthyroidism.

There are two types of cholesterol: high density lipoprotein (HDL) and low density lipoprotein (LDL). In everyday life, they are called, respectively, “useful” and “harmful” cholesterol.

“ Harmful”, or light cholesterol

“Bad” cholesterol are low density lipoproteins, LDL (LDL), which are produced by the liver and are used to transport cholesterol throughout the body.Part of the light cholesterol is produced by the body itself, and the other part is received by our body along with sausage, meat, cream, butter, eggs and fatty dairy products. It is this type of cholesterol, with its excess, can create deposits on the walls of blood vessels and lead to atherosclerosis. For this reason, LDL is not well known. The optimal level of LDL in healthy people is less than 130 mg / dL. Indicators over 160 mg / dL – the risk of developing atherosclerosis, heart attack and other cardiovascular diseases.

“ Useful” or heavy cholesterol

“Good” or heavy cholesterol is a high density lipoprotein called HDL (HDL). They transport excess cholesterol from the walls of blood vessels back to the liver, which constantly processes it and removes it from the body. That is, it removes light cholesterol from the body, which in the form of lipoprotein molecules settles on the walls of blood vessels, turning over the years into atherosclerotic plaques.This is why HDL is called the “good” cholesterol. Therefore, HDL cholesterol levels may be high enough to cope with this task. The optimal level of this indicator is more than 40 mg / dL.

Triglycerides

There are also triglycerides , or neutral fats that enter our body from food. This is a kind of energy reserve in case the body does not receive sufficient energy from the outside.Triglycerides are deposited primarily in adipose tissue and are released as needed. The normal range is 40 to 250 mg / dl. The optimal level is considered to be less than 150 mg / dL. The amount of triglycerides can be increased by alcohol abuse, excessive consumption of sugar and fatty foods, as well as diabetes and obesity.

Is cholesterol illegal?

For a long time, cholesterol was considered the real personification of evil.Cholesterol foods have been outlawed; Various “cholesterol-free” diets were extremely popular. The main charge of cholesterol was based on the fact that it contains atherosclerotic plaques located on the inner surface of the vessels. These plaques are formed during atherosclerosis, disrupting the elasticity and patency of blood vessels, and this, in turn, can lead to complications such as heart attacks, strokes, some brain diseases and many other ailments.In fact, it turned out that for the prevention of atherosclerosis, it is important not only to monitor the level of cholesterol, but also to pay attention to many other factors.

Of particular importance is the state of the nervous system, the level of psychoemotional stress. It has been proven that prolonged stress is one of the main factors that determine the development of atherosclerosis in general and sclerosis of the heart vessels, in particular. Various infectious diseases, the level of physical activity, heredity can also affect the state of blood vessels and provoke the development of atherosclerosis and its complications.

To prevent the development of atherosclerosis, it is not enough to reduce the level of “bad” cholesterol in the body. It is also important to maintain at the proper level “good” cholesterol, without which the normal functioning of internal organs is impossible.

Every day the body of an average person synthesizes from 1 to 5 g of cholesterol. The largest share of cholesterol (80%) is produced in the liver, some is produced by the cells of the body, and only about 300-500 mg of cholesterol comes to us with food.Where is this cholesterol spent? About 20% of the total amount of cholesterol in the body is found in the brain and spinal cord, where this substance is a structural component of the myelin sheath of nerves. In the liver, bile acids are synthesized from cholesterol, which are necessary for the emulsification and absorption of fats in the small intestine. For these purposes, 60-80% of the daily cholesterol formed in the body is spent. A small part (2-4%) goes to the formation of steroid hormones (sex hormones, adrenal cortex hormones, etc.)). A small amount of cholesterol is consumed in the synthesis of vitamin D in the skin (under the influence of ultraviolet rays) and in the retention of moisture in the cells of the body. Thanks to laboratory studies carried out by a group of scientists from Germany and Denmark, it was found that low density lipoproteins – carriers of the so-called “bad” cholesterol are components of blood plasma, which can not only bind, but also neutralize dangerous bacterial toxins. That is, “bad” cholesterol supports the human immune system! Therefore, you just need to make sure that the level of “bad” cholesterol does not exceed the permissible norm, and then everything will be fine!

About cholesterol free diet

What negative effects can the desire for a cholesterol-free diet lead to? In men, a strict adherence to cholesterol-free foods can adversely affect sexual activity, and in women who are too active in the fight against cholesterol, hormonal disruption (amenorrhea) often occurs.Dutch doctors claim that the low content of this substance in the blood is “guilty” of the spread of mental illness. Therefore, experts recommend: if you have depression, do a blood test for cholesterol! Perhaps it is his lack that deprives you of the joy of life …

It is very important that “good” and “bad” cholesterol are balanced in relation to each other. Their ratio is determined as follows: the total cholesterol content is divided by the “good” cholesterol content.The resulting number must be less than six. If there is too little cholesterol in the blood, then this is also bad. The most favorable ratio of “bad” and “good” cholesterol in the blood is observed in people whose proportion of fat in the diet is 40-50 percent. In those who practically do not consume fats, the content of not only “harmful” cholesterol, which is involved in the formation of atherosclerotic plaques, decreases in the blood, but also its beneficial forms, which protect the vessels from atherosclerosis.

According to the official recommendations of the European Society of Atherosclerosis (in Germany it is a very respected organization), “normal” levels of fatty fractions in the blood should be as follows:

• Total cholesterol – less than 5.2 mmol / L.
• Low density lipoprotein cholesterol – less than 3-3.5 mmol / l.
• High density lipoprotein cholesterol – more than 1.0 mmol / l.
• Triglycerides – less than 2.0 mmol / L.

A person’s life expectancy directly depends on his cholesterol levels – this is what many medical specialists believe today. Therefore, you need to know these data and, starting from the age of 18-20, check them every five years. It is impossible to determine this level by appearance, by well-being! For a young “pumped-up” athlete, he can be as high as that of a well-fed pensioner.

How to protect yourself from the development of atherosclerosis and its complications? Is it enough to adhere to a diet for this, or are there other factors in the prevention of this formidable ailment? We will talk about this with you in the following publications.

90,000 Residents of the republic were examined in mobile medical modules

With the support of the Ministry of Health of the Republic of Bashkortostan, within the framework of the all-Russian roadshow “Muzarteria”, a donor holiday was held in Ufa on August 1.On this day, on the square in front of the “Ufa-Arena”, the work of mobile medical modules of the Republican Clinical Hospital named after G.G. Kuvatov (RCH named after G.G. Kuvatov), ​​the Republican Clinical Oncological Dispensary (RKOD), the Republican Cardiological Center ( RCC). Residents and guests of the capital checked their health and received expert advice.

As part of the team of the “Diagnostics” module of the RKB im. G.G. Kuvatova worked as a general practitioner, an obstetrician-gynecologist, a doctor and a nurse for ultrasound diagnostics, a nurse for functional diagnostics.A total of 125 people were admitted, 270 diagnostic examinations were carried out, including ultrasound – 240, ECG – 30.

The survey of the population in the mobile medical center “Women’s Health” RKOD was carried out by a mammologist and general oncologist. In total, 182 women were examined, 56 mammographic examinations were carried out. Two surveyed women with suspected oncopathology were offered examination at the RKOD.

The event was actively supported by the staff of the cardio center. As part of the donor campaign, 25 employees of the medical institution donated blood.Four doctors and four nurses worked in the mobile diagnostic unit. During the field work, the blood pressure was measured in 196 applicants, the level of cholesterol, glucose, triglycerides and LDL – 82 people were determined. 112 patients underwent ECG, 196 people received consultations from cardiologists. During the event, 38 patients with arterial hypertension (19%), 40 patients with disorders of the autonomic nervous system (20%), with coronary heart disease – 16 people (8%) were first identified.All those who applied were given recommendations on the basics of a healthy lifestyle, on risk factors for the development of cardiovascular diseases, 390 leaflets were distributed. The event participants completed 196 screening questionnaires.

Press Service of the Ministry of Health of the Republic of Bashkortostan

Cholesterol-rich foods

Cholesterol-rich foods

Cholesterol-rich foods – sorted list

1

Compare Cholesterol Rich Foods

Caviar is rich in Cholesterol.Caviar contains more Cholesterol than 95% of foods. 100 grams of Black caviar contains 196% of the Cholesterol that you need to consume daily.

richer than 95% foods

In one hundred grams, 196% of the daily dose

Product Black caviar is also rich in substances Sodium , Iron and Ash

2

Compare Cholesterol Rich Foods

Herring fish oil is rich in Cholesterol.Herring Fish Oil contains more Cholesterol than 95% of foods. 100 grams of Herring fish oil contains 190% of the Cholesterol that you need to consume daily.

richer than 95% foods

In one hundred grams 190% of the daily dose

The product Herring fish oil is also rich in substances Calories , Fats and Saturated fats

100%
Calorie content

95%
Saturated fat

3

Compare Cholesterol Rich Foods

Egg is rich in Cholesterol.Egg contains more Cholesterol than 94% of foods. 100 grams of Egg contains 124% of the Cholesterol that you need to consume daily.

richer than 94% foods

In one hundred grams, 124% of the daily dose

Egg product is also rich in substances Vitamin B2 , Vitamin A and Retinol

4

Compare Cholesterol Rich Foods

Liver is rich in Cholesterol.Liver contains more Cholesterol than 94% of foods. 100 grams of Liver contains 118% of the Cholesterol that you need to consume daily.

richer than 94% foods

In one hundred grams, 118% of the daily dose

Product Liver is also rich in substances Iron , Vitamin B2 and Vitamin A

5

Compare Cholesterol Rich Foods

Oil is rich in Cholesterol.Butter contains more Cholesterol than 94% of foods. 100 grams of Butter contains 72% of the Cholesterol that you need to consume daily.

richer than 94% foods

In one hundred grams 72% of the daily dose

The product Oil is also rich in substances Fats , Calories and Saturated fats

98%
Calorie content
96%
Saturated fat

6

Compare Cholesterol Rich Foods

Shrimp is rich in Cholesterol.Shrimp contains more Cholesterol than 93% of foods. 100 grams of Shrimp contains 63% of the Cholesterol that you need to consume daily.

richer than 93% foods

In one hundred grams 63% of the daily dose

The product Shrimp is also rich in substances Proteins , Copper and Phosphorus

7

Compare Cholesterol Rich Foods

Biscuit is rich in Cholesterol.Biscuit contains more Cholesterol than 93% of foods. 100 grams of Biscuit contains 57% of the Cholesterol that you need to consume daily.

richer than 93% foods

In one hundred grams 57% of the daily dose

The product Biscuit is also rich in substances Carbohydrates , Vitamin B2 and Retinol

8

Compare Cholesterol Rich Foods

Sardine is rich in Cholesterol.Sardine contains more Cholesterol than 93% of foods. 100 grams of Sardine contains 47% of the Cholesterol that you need to consume daily.

richer than 93% foods

In one hundred grams, 47% of the daily dose

The product Sardine is also rich in substances Calcium , Phosphorus and Ash

9

Compare Cholesterol Rich Foods

Port-Salu is rich in Cholesterol.Port-Salu contains more Cholesterol than 92% of foods. 100 grams of Port-Salu contains 41% of the Cholesterol that you need to consume daily.

richer than 92% foods

In one hundred grams 41% of the daily dose

Port-Salu is also rich in substances Calcium , Saturated fat and Fat

93%
Saturated fat

10

Compare Cholesterol Rich Foods

Turkey is rich in Cholesterol.Turkey contains more Cholesterol than 90% of foods. 100 grams of Turkey contains 36% of the Cholesterol that you need to consume daily.

richer than 90% of foods

In one hundred grams, 36% of the daily dose

Turkey is also rich in substances Proteins , Vitamin B3 and Vitamin B6

11

Compare Cholesterol Rich Foods

Cheese Romano is rich in Cholesterol.Romano Cheese contains more Cholesterol than 89% of foods. 100 grams of Romano Cheese contains 35% of the Cholesterol that you need to consume daily.

richer than 89% foods

In one hundred grams 35% of the daily dose

The product Romano cheese is also rich in substances Proteins , Sodium and Calcium

12

Compare Cholesterol Rich Foods

Largemouth bass is rich in Cholesterol.Largemouth bass contains more Cholesterol than 89% of foods. 100 grams of Largemouth bass contains 34% of the Cholesterol that you need to consume daily.

richer than 89% foods

In one hundred grams 34% of the daily dose

Product Largemouth bass is also rich in Proteins , Vitamin B12 and Magnesium

13

Compare Cholesterol Rich Foods

Cream cheese is rich in Cholesterol.Cream cheese contains more Cholesterol than 89% of foods. 100 grams of Cream cheese contains 34% of the Cholesterol that you need to consume daily.

richer than 89% foods

In one hundred grams 34% of the daily dose

Product Cream cheese is also rich in substances Fats , Saturated fat and Monounsaturated fat

94%
Saturated fat
82%
Monounsaturated fat

14

Compare Cholesterol Rich Foods

Cheese is rich in Cholesterol.Cheese contains more Cholesterol than 88% of foods. 100 grams of Cheese contains 33% of the Cholesterol that you need to consume daily.

richer than 88% foods

In one hundred grams 33% of the daily dose

Product Cheese is also rich in substances Fats , Calcium and Saturated fat

94%
Saturated fat

15

Compare Cholesterol Rich Foods

Crab is rich in Cholesterol.Crab contains more Cholesterol than 88% of foods. 100 grams of Crab contains 32% of the Cholesterol that you need to consume daily.

richer than 88% foods

In one hundred grams 32% of the daily dose

The product Crab is also rich in substances Sodium , Copper and Vitamin B12

16

Compare Cholesterol Rich Foods

Lamb is rich in Cholesterol.Lamb contains more Cholesterol than 88% of foods. 100 grams of Lamb contains 32% of the Cholesterol that you need to consume daily.

richer than 88% foods

In one hundred grams 32% of the daily dose

Lamb product is also rich in substances Proteins , Saturated fats and Fats

86%
Saturated fat

17

Compare Cholesterol Rich Foods

Mackerel is rich in Cholesterol.Mackerel contains more Cholesterol than 87% of foods. 100 grams of Mackerel contains 32% of the Cholesterol that you need to consume daily.

richer than 87% foods

In one hundred grams 32% of the daily dose

Mackerel is also rich in substances Sodium , Ash and Fats

18

Compare Cholesterol Rich Foods

Brunost is rich in Cholesterol.Brunost contains more Cholesterol than 87% of foods. 100 grams of Brunost contains 31% of the Cholesterol that you need to consume daily.

richer than 87% foods

In one hundred grams 31% of the daily dose

Brunost is also rich in Saturated Fat , Potassium and Fat

94%
Saturated fat

19

Compare Cholesterol Rich Foods

Roquefort is rich in Cholesterol.Roquefort contains more Cholesterol than 85% of foods. 100 grams of Roquefort contains 30% of the Cholesterol that you need to consume daily.

richer than 85% foods

In one hundred grams 30% of the daily dose

Roquefort is also rich in Sodium , Ash and Calcium

20

Compare Cholesterol Rich Foods

Beef is rich in Cholesterol.Beef contains more Cholesterol than 84% of foods. 100 grams of Beef contains 29% of the Cholesterol that you need to consume daily.

richer than 84% foods

In one hundred grams, 29% of the daily dose

Product Beef is also rich in substances Proteins , Zinc and Saturated fat

79%
Saturated fat

x

Compare Caviar to other rich in Cholesterol

foods

x

Compare Herring Fish Oil to Other Cholesterol

Foods

x

Compare Egg to other foods rich in Cholesterol

x

Compare Liver to other foods that are rich in Cholesterol

x

Compare Butter to other foods rich in Cholesterol

x

Compare Shrimp to other foods rich in Cholesterol

x

Compare Sponge cake to other rich in Cholesterol

foods

x

Compare Sardine to other foods that are rich in Cholesterol

x

Compare Port-Salu to other cholesterol

rich foods

x

Compare Turkey to other foods that are rich in Cholesterol

x

Compare Romano Cheese with other cholesterol-rich foods

x

Compare Largemouth bass to other rich in Cholesterol

foods

x

Compare Cream cheese to other rich in Cholesterol

foods

x

Compare Cheese to other foods rich in Cholesterol

x

Compare Crab to other rich in Cholesterol

foods

x

Compare Lamb meat to other cholesterol

rich foods

x

Compare Mackerel to other rich in Cholesterol

foods

x

Compare Brunost to other rich in Cholesterol

foods

x

Compare Roquefort to other rich in Cholesterol

foods

x

Compare Beef to other foods rich in Cholesterol

Please consult your healthcare professional before starting any diet.

© FoodStruct 2016 – 2021

How obesity worsens heart condition and what to do about it?

How obesity worsens heart condition and what to do about it?

Obesity is associated with a variety of health problems such as arthritis, cancer, heart disease, lung disease, and gallbladder disease.

Obese people tend to have a poorer quality of life, and die earlier than people with a normal body mass index (BMI).

How obesity affects the heart

Obesity can lead to many diseases, but one of the biggest problems is the harms of obesity to the heart. It has long been known that obese people tend to have higher blood pressure, high bad cholesterol, and lower good cholesterol.

Obesity also leads to insulin resistance. Over time, insulin resistance causes higher blood sugar levels, which ultimately leads to diabetes.

High blood pressure, high cholesterol, and diabetes are known risk factors for heart disease, and the more of these factors you have, the higher your risk of heart disease.

Even if you don’t have one of these factors, your heart is still in danger. Severely obese people have a fourfold increased risk of developing heart failure.

Research shows that the link between obesity and heart failure persists regardless of the presence of other risk factors.This means that if you are obese, you are still at increased risk of heart failure, even if you do not have high blood pressure, high cholesterol, or diabetes.

How obesity develops heart failure

Heart failure is a growing problem in all developed countries. People who suffer from it feel short of breath and are unable to do their normal daily activities normally.They also tend to accumulate excess fluid in the body, leading to swelling around the ankles.

Heart failure is a very serious condition that not only impairs your quality of life, but also endangers your very life. About half of people diagnosed with heart failure die within the next five years.

Obesity leads to heart failure in several ways. Excess body fat leads to an increase in blood volume, which makes your heart work harder to pump all this “extra” blood.Over the course of several years, this causes harmful changes in the structure of the heart and its function, which ultimately lead to heart failure.

Fatty tissue, especially in the abdomen, is harmful by producing a number of toxic substances such as cytokines and adipokines that damage the muscles of the heart. Obese people, even without any clear signs of heart disease, can actually suffer chronic damage to their heart muscle. It is clear that in the end it does not end with anything good.

What to do

Yes, fighting obesity is difficult. But there are some positive facts that will help you in your war for health and a high quality of life:

Any weight loss is good for you. In fact, a weight loss of only 3-5% will reduce bad cholesterol as well as blood glucose levels. Further weight loss will help lower blood pressure and further decrease bad cholesterol as well as increase good cholesterol.There is even some evidence that losing weight can reverse some of the damage to the heart as well as dysfunction of the heart.

Causes of obesity of the heart

Overweight

Such a phenomenon as obesity of the heart can have a variety of reasons. But the main thing is an overweight person. After all, excess fat is deposited not only in prominent places under the skin (belly, thighs, etc.), but also in the internal organs, whose work is disrupted by this.

The main cause of obesity is a persistent, significant preponderance of the intake of nutrients in the body over their expenditure. Since the body always uses the energy of the more easily digestible carbohydrates in the first place, it starts to break down fats only in case of a lack of energy. And if there is enough of that, then the fats that have entered the body are unclaimed. As a result, excess energy in the form of undigested fats is deposited in fat cells.

Alcohol abuse also contributes to obesity. In this regard, beer turns out to be much more harmful than wine and even vodka, since it contains much more carbohydrates (a daily dose in 5-6 glasses of a foamy drink). Ethanol itself is easily oxidized and gives up its energy, slowing down the metabolism of fats circulating in the body. In addition, often drinkers lead a sedentary lifestyle, they have physical and mental lethargy.

Heredity

A factor of hereditary predisposition can also lead to obesity of the heart. Such people may outwardly look not very fat, however, excess fat can be deposited in their internal organs (heart, liver, etc.), which begins to interfere with their work.

Symptoms of obesity of the heart

Shortness of breath becomes the first noticeable symptom in obese people. If the obesity of the heart has reached a severe form, then shortness of breath does not go away even in a calm state.Such patients are not only unable to exercise, but cannot even go up to the second floor.

· Heart pain is an important symptom of obesity in the heart. When the muscles of the myocardium degenerate and grow into adipose tissues, the organ weakens.

Arrhythmia. In an obese heart, the rhythm of the work fails, which is expressed in the appearance of tachycardia and the development of other serious pathologies.

· Very often, with obesity, blood pressure rises, and to very high values.Hypertension itself causes secondary pathological processes that damage other organs and systems, for example, the central nervous system.

Sometimes people complain that some point above their heart hurts in one place and they believe that it is the heart that hurts. But in reality, this may be a sign of problems in a completely different system: from the digestive to the genitourinary. If a person feels any discomfort, then he should, without delay, consult a doctor who will prescribe the necessary studies.