Lipid Dysregulation and Hyperlipidemia
In recent years cholesterol has gotten a bad rap. This recent phenomenon started in the 1950’s when heart disease was the leading cause of death in the United States, and scientists turned their mind to trying to figure out why. (Berge, 2008) The birth of the diet heart hypothesis can be contributed to Ancil Keys, a physiologist at the University of Minnesota. Keys famously conducted an epidemiological longitudinal study called the seven countries study. What he was able to show with this study was a positive correlation between the intake of dietary saturated fat, total serum cholesterol and cardiovascular disease. His conclusion, which he published more than 20 papers on between 1957 and 1985, was that dietary cholesterol intake caused high blood serum cholesterol and subsequently heart disease and thus the diet heart hypothesis was born. (Teicholz, 2023) Further studies that followed seemed to lend credence to this hypothesis.
However, the data from the Seven Countries Study has been called into question in more recent times. Keys had data for 22 countries to look at, but only included 7 of them in his final analysis and papers. If you look at the data from all 22 countries that was available at that time, there is no statistical significance in the relationship between dietary cholesterol intake and CVD. Keys himself, in a New York Times article published in 1987, said “I’ve come to think cholesterol isn’t as important as we used to think it was.” (Boffey, 1987)
In 1980 the US released the first Dietary Guidelines for Americans promoting a low-fat diet. This was readily adopted by health professionals, doctors and the food industry, and the downfall of dietary cholesterol formally began in the US. (Agneta Yngve PhD, 2010) This diet was touted as the gold standard for preventing cardiovascular disease (CVD). On the surface, this seemed to work and be a good thing for the American people. While CVD remained the leading cause of death, the overall numbers were declining. However, if you look closer at those numbers, incidences of CVD had been in decline since the mid 1960’s and experts are fearful that we will see an increase in CVD for the current generation. (David S. Jones, 2013)
The demonizing of cholesterol by public and private institutions has had an impact on the health of American’s because, despite its bad reputation, cholesterol is a highly important nutrient that has many health protecting properties. It is so important to the human body, that we make 80% of our body’s cholesterol endogenously in the liver. Only 20% of our total cholesterol comes from dietary intake, so reducing dietary intake doesn’t have a very big impact on reducing total cholesterol levels. (Nora T. Gedgaudas, 2011) There are even studies that show low total serum cholesterol was correlated with increased mortality from all causes, and that increasing dietary cholesterol intake reduces the production of endogenous cholesterol. (Naoki Nago 1, 2010) (Jeong, 2018) These facts lend themselves to the argument that cholesterol is a nutrient that is essential for health and well-being.
What is a problem when it comes to cholesterol, health, and CVD, is the ratio of high-density lipoproteins (HDL) to low density lipoproteins (LDL), the amount of very low-density lipoproteins (VLDL), and the ratio of total cholesterol to HDL. These ratios are a better indicator of cardiovascular health, as they tell us if the cholesterol is being deposited into tissues or being excreted out of the body. Total cholesterol to HDL should be less than 4.2, while LDL to HDL should be less than 2.5. Small dense VLDL particles are specifically associated with an increase in CVD and atherosclerosis as these molecules are oxidized and pro inflammatory which cause damage to blood vessels. Contrary to dietary guidelines in the past, low fat diets actually increase this type of LDL in the body.
Endogenous cholesterol starts as Acetyl-CoA which reacts with the enzyme HMG-CoA reductase, and through a long series of chemical reactions produces cholesterol and Co-enzyme Q 10 (CoQ10). (Milessa Silva Afonso, 2018) The HMG-CoA reductase enzyme is what statin drugs target because reducing the function of this enzyme in turn reduces the amount of endogenous cholesterol that is made. However, we can look at what naturally upregulates that enzyme and reduce its effects through a more holistic approach. A lack of dietary cholesterol intake and an excess intake of sugar, which increases insulin, upregulates this enzyme which results in an increase of cholesterol production. (Jussi Pihlajamäki, 2004).
Cholesterol is a necessary nutrient for so many functions in the body including vitamin D synthesis, sex hormone production, mineralocorticoid and glucocorticoid production, bile salt production, inflammation reduction, and repair of bodily tissues in response to inflammation. (Craig, Yarrarapu, & Dimri., 2023). Cholesterol also comprises about 30% of fats in cell membranes and acts as an important component of the membrane. Cholesterol helps keep the membrane fluid, which is important for proper cell signaling as it allows for imbedded proteins to change shape properly, it helps regulate permeability of the membrane and is a large component of brain, which is roughly 60% saturated fat, and nervous tissue.
Normal cholesterol levels are defined as 130-200 mg/dL in conventional labs, while the optimal range is typically set at 150-200 mg/dL. Total cholesterol is considered to be high if it is above 400 mg/dL, or low if It’s under 50 mg/dL. (Dicken Weatherby, 2002). Cholesterol levels are raised for a variety of reasons in the body, and if left unchecked they can lead to a medically relevant rise in cholesterol levels. Excess sugar intake increases the hormone insulin in the body, which I previously stated upregulates the enzyme HMG-CoAR increasing cholesterol production. Additionally, dietary intake of high fructose corn syrup and trans fats increase total cholesterol. While dietary intake of saturated fats also increases cholesterol levels, not all saturated fats are the same. Stearic acid and lauric acid are two types of saturated fats that do not show an increase in total cholesterol within the body.
In addition to specific foods that increase cholesterol, hypothyroid issues can also be a contributing factor to high cholesterol. The primary hormones released by the thyroid are T3 and T4, which act, in part, to regulate lipid metabolism and recycle cholesterol. Thyroid hormones do this by increasing the production of bile salts, increasing LDL receptors on cells, and increasing HDL metabolism. (Rohit A. Sinha, 2018)
There are many dietary and holistic approaches to lowering total cholesterol and optimizing the ratios of LDL to HDL and total cholesterol to HDL, which are a more accurate measure of CVD risk than total cholesterol alone. One of the most studied is the intake of soluble fiber and its effect on cholesterol. (Soliman, 2019) Soluble fiber binds to cholesterol in the large intestine and excretes it out of the body. The recommended daily amount of fiber for men 19-50 is 38g/day and for women it’s 25g/day, although, on average, Americans only consume 10-15 g/day (Katherine D. McManus, 2019). In order for the cholesterol lowering effects to be observed, the recommend daily amount of fiber is 30-35g. This is why we often see much better health markers when people switch from a SAD diet to a vegetarian, vegan, or Mediterranean type diet. That switch has less to do with dietary cholesterol intake and more to do with a sharp increase in fiber intake.
Consuming higher amounts of phytosterols is also a holistic nutritional intervention that can help reduce total cholesterol and optimize important cholesterol ratios. Phytosterols bind to cholesterol receptors in the gut preventing its absorption through the intestinal lining. (Klein, 2017) This is another nutrient that is naturally increased on a vegan, vegetarian, or Mediterranean type diet as it’s found mostly in green foods such as avocado, chard, kale, spinach and other leafy greens, olive oil, and sunflower seeds.
As far as supplements go, red rice yeast, an ancient Chinese product, has been shown to reduce LDL and total cholesterol in patients with high cholesterol. (D Heber, 1999) Red rice yeast contains a substance called monacolin K, which is one of the substances found in statin drugs. Monacolin K inhibits the enzyme HMG-CoAR which in turns reduces total endogenous cholesterol production. (Cicero, 2019) Dosage that has been shown to reduce cholesterol is between 200-4800 mg/day in a divided dose.
In conclusion, cholesterol is not the horrible nutrient we have been conditioned to think it is. Science clearly shows that the diet heart hypothesis has many holes and doesn’t tell the whole picture of how cholesterol works in the body. It is an extremely important nutrient, and if we do not consume it, our bodies are making it. It’s the general increase in carbohydrate consumption, in replacement of dietary fats, that has contributed to the increase in cholesterol levels and CVD. Cholesterol has an important place in the diet, and dietary interventions to lower CVD risk should be focused on optimizing cholesterol ratios and reducing insulin production in the body instead of decreasing total cholesterol.
Cholesterol Lowering Recipe: Mediterranean Lentil Salad
· ½ lb. Lentils soaked for 12 hrs.
· ½ cup olive oil
· ¼ cup red wine vinegar
· 1 TBS Dijon mustard
· 2 cloves garlic minced
· 1 tsp dried oregano
· Sea salt and pepper to taste
· 2 cups grape tomatoes quartered
· 2 cups cucumber diced
· 1 cup pitted Kalamata olives
· ½ red onion diced
· 8 oz. feta cheese cubed or crumbled
· Fresh herbs (basil, parsley, thyme, mint etc.) to taste
Bring 3 cups of water to a boil. Add lentils and simmer until tender, about 20 minutes. Drain well and spread on baking sheet to cool.
In a small bowl, whisk together dressing: olive oil, red wine vinegar, mustard, garlic, and oregano. Season with salt and pepper to taste.
In a large bowl combine cooled lentils, tomatoes, cucumbers, olives, red onion, and feta cheese. Drizzle with vinaigrette dressing. Toss to combine and top with fresh herbs if desired.
10-1 cup servings 209 calories 17g carbs 7g protein 13g fat 8g fiber
Beneficial nutrients in this recipe include: lentils which have a high amount of fiber, garlic which has been shown to reduce HMG-CoAR activity, tomatoes have niacin which raises HDL while lowering LDL and triglycerides, and feta cheese which has Omega 3 FA which lower triglycerides, increase HDL and inhibit VLDL production.
References
Agneta Yngve PhD,
M. M. (2010). A Historical Perspective of the Understanding of the Link between Diet and Coronary Heart Disease. American Journal of Lifestyle Medicine, 35-38.
Berge, A. F. (2008). How the Ideology of Low Fat Conquered America . Journal of the History of Medicine and Allied Sciences, 139-177.
Boffey, P. M. (1987, July 14th). Cholesterol: Debate Flares Over Wisdom In Widespread Reductions. Retrieved from New York Times: https://www.nytimes.com/1987/07/14/science/cholesterol-debate-flares-over-wisdom-in-widespread-reductions.html
Cicero, A. F. (2019). Red Yeast Rice for Hypercholesterolemia. Methodist DeBakey Cardiovascular Journal, 192-199.
Craig, M., Yarrarapu, S. N., & Dimri., M. (2023). Biochemistry, Cholesterol. In StatsPearl. Treasure Island: StatPearls Publishing.
D Heber, I. Y. (1999). Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. American Journal of Clinical Nutrition, 231-236.
David S. Jones, M. P. (2013). The Decline and Rise of Coronary Heart Disease: Understanding Public Health Catastrophism. American Journal of Public Health, 1207-1218.
Dicken Weatherby, N. a. (2002). Blood Chemistry and CBC Analysis: Clinical Laboratory Testing from a Functional Perspective. Jacksonville: Bear Mountain Publishing.
Jeong, S.-M. (2018). Association of change in total cholesterol level with mortality: A population-based study. PLOS One.
Jussi Pihlajamäki, H. G. (2004). Insulin resistance is associated with increased cholesterol synthesis and decreased cholesterol absorption in normoglycemic men. Journal of Lipid Research , 507-512.
Katherine D. McManus, M. R. (2019, February 27). Harvard Health. Retrieved from Harvard Health Blog: Should I be eating more fiber?: https://www.health.harvard.edu/blog/should-i-be-eating-more-fiber-2019022115927#:~:text=Fiber%3A%20how%20much%20is%20enough,and%2030%20daily%20grams%2C%20respectively.
Klein, C. E. (2017). Phytosterols in the Treatment of Hypercholesterolemia and Prevention of Cardiovascular Diseases. Arq Bras Cardiol, 475-482.
Milessa Silva Afonso, R. M. (2018). Molecular Pathways Underlying Cholesterol Homeostasis. Nutrients, 760.
Naoki Nago 1, S. I. (2010). Low cholesterol is associated with mortality from stroke, heart disease, and cancer: the Jichi Medical School Cohort Study. Journal of Epidemiology , 67-74.
Nora T. Gedgaudas, C. C. (2011). Primal Body, Primal Mind. Rochester: Healing Arts Press.
Rohit A. Sinha, B. K. (2018). Direct effects of thyroid hormones on hepatic lipid metabolism. Nat Rev Endocrinol, 259-269.
Soliman, G. A. (2019). Dietary Fiber, Atherosclerosis, and Cardiovascular Disease. Nutrients.
Teicholz, N. (2014). The Big Fat Surprise: Why Butter, Meat and Cheese Belong in a Healthy Diet. New York: Simon & Schuster.
Teicholz, N. (2023). A short history of saturated fat: the making and unmaking of a scientific consensus. Curr Opin Endocrinol Diabetes Obes, 65-71.
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