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August 19, 2021

Cholesterol: Optimal Ranges for Total Cholesterol Summary

In this post, the ODX Research team evaluates the role cholesterol plays in human metabolism and proposes a new optimal range for Total Cholesterol.

Cholesterol: Optimal Range for Total Cholesterol

Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN

Cholesterol is much more than just a popular topic. It’s a vital compound that is required for numerous functions, which is why it can be produced by just about every cell in the body.

It is a structural and functional element of cell membranes, a major lipid in the brain and central nervous system, and a precursor to all steroid hormones, vitamin D, and bile salts.[1] [2]

Most importantly, cholesterol is essential to nerve transmission and neural function; cell membrane fluidity and permeability; growth and development; digestion and absorption; vitamin D synthesis; stress response; blood pressure; and fluid and salt balance.

Cholesterol and Disease Risk

Elevations in total cholesterol had been considered a risk factor for cardiovascular disease (CVD) in the past. However, research revealed that as a standalone biomarker, total cholesterol doesn’t provide enough information about cardiovascular risk.

We also need to know how cholesterol is carried (various lipoproteins including VLDL, IDL, LDL, HDL), whether it’s become oxidized (much more dangerous), and whether excess is due to hypercholesterolemia, a genetic disorder that fails to regulate cholesterol production.[3] [4]

We also know that it’s important to assess downstream metabolites of cholesterol, including glucocorticoids, mineralocorticoids, sex hormones, and vitamin D in order to understand an elevated or decreased total cholesterol. Disruption of cholesterol metabolism may affect the many functions that its metabolites regulate.

Assessing cardiovascular risk using only total cholesterol will not reveal some of the most important CVD risk factors that we know of. These include inflammation; oxidative stress; an unhealthy highly processed diet; excess toxin exposure; and blood glucose dysregulation. Other biomarkers must be assessed when evaluating CVD risk including inflammatory markers such as hs-CRP and homocysteine.

Total Cholesterol Levels: Highs and Lows

Highly elevated total cholesterol above 350 mg/dL (9 mmol/L) is usually associated with a genetic disorder called familial hypercholesterolemia. This disorder is also associated with highly elevated LDL and non-HDL cholesterol.[5]

Total cholesterol may rise above 200 mg/dL (5.2 mmol/L) in the absence of familial hypercholesterolemia. This above optimal level should be monitored and addressed, especially for those at increased risk of cardiovascular disease, inflammation, and oxidative stress. Cholesterol excess can also build up and contribute to liver dysfunction if not processed properly.[6]

In those with low risk of CVD and oxidative stress, total cholesterol up to 249 mg/dL (6.5 mmol/L) may be acceptable depending on lipoprotein breakdown and characteristics.[7] Total cholesterol above 180 mg/dL (4.66 mmol/L) may be protective in Parkinson’s disease.[8] [9]

A low total cholesterol may be indicative of malnutrition and increased risk of psychological disorders, neurodegenerative disease, and all-cause mortality, especially if levels drop below 160 mg/dL (4.14 mmol/L).[10] [11] [12] Total cholesterol below 145 mg/dL (3.78 mmol/L) is associated with increased risk of depression and suicidal ideation.[13] [14]

Healthy middle-aged individuals with total cholesterol below 160 mg/dL had significantly greater mortality from heart failure, hemorrhagic stroke, and cancer compared to moderate total cholesterol levels of 160-200 mg/dL (4.14–5.2 mmol/L). In this group of 12,334 individuals, levels 239 mg/dL (6.2 mmol/L) or greater were not found to be associated with increased risk of death.[15]

Cholesterol and Hormone Balance

Since cholesterol is the precursor to glucocorticoids, mineralocorticoids, sex hormones, and vitamin D, a disruption in its metabolism can affect the balance of downstream metabolites. For example, statin-induced inhibition of cholesterol synthesis was associated with declines in serum testosterone.[16] [17] Statins can also deplete CoQ10 by up to 40% which is especially detrimental in those with heart failure, diabetes, or who are elderly.[18]

Cholesterol metabolism is regulated by the thyroid gland and elevated levels are associated with hypothyroidism. Administration of thyroid hormone reduced elevated cholesterol (initially above 290 mg/dL (7.5 mmol/L) in those with TSH above optimal who had elevated thyroid autoantibodies.[19]

As you can see, cholesterol is an indispensable compound that is produced in the body for a number of reasons. It is especially important to cell membrane integrity; brain and nervous system function; and hormone and vitamin D synthesis.

Total cholesterol levels above optimal should be evaluated on an individual basis, including a full assessment of genetic hypercholesterolemia (if 350 mg/dL and above); cardiovascular risk; lipoprotein breakdown, particle size, and number; thyroid function; hormone balance; and neurodegenerative risk.

Levels below optimal should prompt an evaluation of nutrition status; neurological and mood impacts; and risk of heart failure and stroke.

An optimal range for total cholesterol would be 160-199 mg/dL (4.14-5.15 mmol/L).

Want to dive deeper into this topic?

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[1] Huff, Trevor, et al. “Physiology, Cholesterol.” StatPearls, StatPearls Publishing, 15 April 2020.

[2] Schade, David S et al. “Cholesterol Review: A Metabolically Important Molecule.” Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists vol. 26,12 (2020): 1514-1523. doi:10.4158/EP-2020-0347

[3] Ivanova, Ekaterina A et al. “Small Dense Low-Density Lipoprotein as Biomarker for Atherosclerotic Diseases.” Oxidative medicine and cellular longevity vol. 2017 (2017): 1273042. doi:10.1155/2017/1273042

[4] Gao, Shen et al. “Circulating Oxidized Low-Density Lipoprotein Levels Independently Predict 10-Year Progression of Subclinical Carotid Atherosclerosis: A Community-Based Cohort Study.” Journal of atherosclerosis and thrombosis vol. 25,10 (2018): 1032-1043. doi:10.5551/jat.43299

[5] Pejic, Rade N. “Familial hypercholesterolemia.” The Ochsner journal vol. 14,4 (2014): 669-72.

[6] Püschel, Gerhard P, and Janin Henkel. “Dietary cholesterol does not break your heart but kills your liver.” Porto biomedical journal vol. 3,1 e12. 29 Jun. 2019, doi:10.1016/j.pbj.0000000000000012

[7] Yi, Sang-Wook et al. “Total cholesterol and all-cause mortality by sex and age: a prospective cohort study among 12.8 million adults.” Scientific reports vol. 9,1 1596. 7 Feb. 2019, doi:10.1038/s41598-018-38461-y Open Access This article is licensed under a Creative Commons Attribution 4.0 International License. .

[8] Rozani, Violetta et al. “Higher serum cholesterol and decreased Parkinson's disease risk: A statin-free cohort study.” Movement disorders : official journal of the Movement Disorder Society vol. 33,8 (2018): 1298-1305. doi:10.1002/mds.27413

[9] Huang, Xuemei et al. “Serum cholesterol and the progression of Parkinson's disease: results from DATATOP.” PloS one vol. 6,8 (2011): e22854. doi:10.1371/journal.pone.0022854.

[10] Nago, Naoki et al. “Low cholesterol is associated with mortality from stroke, heart disease, and cancer: the Jichi Medical School Cohort Study.” Journal of epidemiology vol. 21,1 (2011): 67-74. doi:10.2188/jea.je20100065

[11] Schatz, I J et al. “Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study.” Lancet (London, England) vol. 358,9279 (2001): 351-5. doi:10.1016/S0140-6736(01)05553-2 

[12] Wu, Bing et al. “Dose-response relation between serum total cholesterol levels and overall cancer risk: evidence from 12 prospective studies involving 1,926,275 participants.” International journal of food sciences and nutrition vol. 70,4 (2019): 432-441.

[13] Messaoud, A et al. “Is low total cholesterol levels associated with suicide attempt in depressive patients?.” Annals of general psychiatry vol. 16 20. 17 Apr. 2017, doi:10.1186/s12991-017-0144-4

[14] Tomson-Johanson K, Harro J. Low cholesterol, impulsivity and violence revisited. Curr Opin Endocrinol Diabetes Obes. 2018;25(2):103-107. doi:10.1097/MED.0000000000000395

[15] Nago, Naoki et al. “Low cholesterol is associated with mortality from stroke, heart disease, and cancer: the Jichi Medical School Cohort Study.” Journal of epidemiology vol. 21,1 (2011): 67-74. doi:10.2188/jea.je20100065

[16] Baspınar, Osman et al. “The effects of statin treatment on adrenal and sexual function and nitric oxide levels in hypercholesterolemic male patients treated with a statin.” Journal of clinical lipidology vol. 10,6 (2016): 1452-1461. doi:10.1016/j.jacl.2016.09.004

[17] Dobs, A S et al. “Effects of high-dose simvastatin on adrenal and gonadal steroidogenesis in men with hypercholesterolemia.” Metabolism: clinical and experimental vol. 49,9 (2000): 1234-8. doi:10.1053/meta.2000.7716a

[18] Zozina, Vladlena I et al. “Coenzyme Q10 in Cardiovascular and Metabolic Diseases: Current State of the Problem.” Current cardiology reviews vol. 14,3 (2018): 164-174. doi:10.2174/1573403X14666180416115428

[19] Michalopoulou, G et al. “High serum cholesterol levels in persons with 'high-normal' TSH levels: should one extend the definition of subclinical hypothyroidism?.” European journal of endocrinology vol. 138,2 (1998): 141-5. doi:10.1530/eje.0.1380141

Tag(s): Biomarkers

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