Publish Date

March 26, 2003

CHOLESTEROL BALANCE – DEFICIENCY & EXCESS

Low cholesterol has been connected to depression, anxiety, bipolar disorder and statistically higher frequency of violent behavior, suicide, Parkinson’s disease, and cancer mortality. Susceptibilities to tuberculosis and gastrointestinal infections are also associated with lower cholesterol levels. Most significantly, the death rate is doubled in older adults with lower total cholesterol and stroke and cataracts rates are higher.

Cholesterol is a sterol essential to life and is found in every animal cell. Cholesterol is part of our cellular structure and protects our tissues. Many people fear and focus on high cholesterol levels, yet never focus on low cholesterol levels, which can have negative health effects. Like everything in nature, balance is the key.

High cholesterol is statistically associated with greater risk of cardiovascular disease (CVD), but less well known is the association of low cholesterol with poor health and many chronic disorders. Recent studies have suggested strongly that lower cholesterol does not guarantee a long life or high quality of life.

The Great Plains Laboratory, Inc. (GPL) offers the Advanced Cholesterol Profile. This profile is used to determine whether a cholesterol deficiency is present or if cholesterol is elevated. This profile also determines if the body is eliminating potentially toxic homocysteine and determines risk factors for vascular disease and/or neurological disease.

BENEFITS OF CHOLESTEROL

Cholesterol serves several important roles in metabolism: it is a key constituent of all cell membranes and provides the structural framework of vitamin D and adrenal and sex hormones, as well as for bile acids which help digest fat and increase absorption of fat soluble vitamins. Most cholesterol is made in the liver and is so crucial to metabolism that, if necessary, it can be synthesized from either fatty acids or glucose. 

The Brain is the Most Cholesterol-Rich Organ in the Body

Cholesterol synthesized in the brain is the primary component of the myelin that surrounds each nerve cell as a protective sheath. Loss of myelin from disease or injury inevitably causes neurological damage. Both neurons and glial (support) cells in the central nervous system (CNS) contain unbound cholesterol as an integral part of their cell membranes.

CHOLESTEROL & CARDIOVASCULAR DISEASE

High cholesterol may be associated with the onset of CVD, but cholesterol may be deposited as a “patch” on inflamed or injured blood vessels, particularly coronary arteries. Macrophages scavenge cholesterol along with other cell debris and may become “foam cells” which accumulate in artery walls and cause atherosclerotic streaks. Assessments of inflammation such as C-reactive protein (test available at GPL) or homocysteine level have been suggested as better predictors of CVD risk.

Homocysteine (Hcy) is a non-protein, non-structural amino acid that is generated by metabolism of methionine, an essential amino acid. Homocysteine can be recycled back to methionine with folic acid and vitamin B-12 as co-factors.

LOW CHOLESTEROL ASSOCIATED WITH MENTAL DISORDERS & MORTALITY IN ELDERLY

Understanding the health consequences of lower cholesterol has been aided by studying serious genetic disorders that prevent cholesterol synthesis in the body. Low choles-terol has been connected to greater risks of suicide, accidents, violence, and mood disorders, such as depression.

Cholesterol levels may influence serotonin activity in the brain. Serotonin is the neurotransmitter associated with mood, and low serotonin is associated with depression and violent and anti-social behavior. Several theories about how cholesterol levels are related to serotonin levels have been proposed. The simplest effect may be that if cholesterol in the nerve cell membrane is deficient, serotonin cannot properly bind to its receptor. Cholesterol also stabilizes receptors for the social-bonding hormone oxytocin.

In the elderly, studies over several decades have pointed to increased risk of death in the population with the lowest cholesterol. Falling cholesterol in the elderly is a sign of increasing morbidity, with controversy over whether it is a sign of underlying chronic disease or a cause of disease. 

TESTING CHOLESTEROL WITH THE GREAT PLAINS LABORATORY, INC.

The Advanced Cholesterol Profile is useful for adults whose low cholesterol may put them at risk for mood disorders or infectious disease. Medical historians have noted that tuberculosis has been uncommon in the USA since the Great Depression, during which high cholesterol foods were unavailable to many because of financial hardship. Vegetarians also have a much higher incidence of tuberculosis than meat eaters. Pregnant women with low cholesterol are twice as likely to have premature babies or babies with small heads.

In addition to total cholesterol, the Advanced Cholesterol Profile includes Apolipoprotein A-I and Apolipoprotein B, Lipoprotein (a) , and Homocysteine.

Lipoproteins are enclosures of protein carrying water-insoluble fat (cholesterol and triglycerides) for transport in the bloodstream and through cellular and mitochondrial membranes. Apolipoproteins have a detergent-like structure that allows them to interface on the outside with aqueous blood and with the lipids bound to the inside. These specialized proteins also serve as enzyme co-factors and receptor ligands (receptor interactions control cholesterol synthesis, transport, and metabolism).

TOTAL CHOLESTEROL

Total cholesterol is the same measure in all lipid panels. Low values (generally values less than 4.14 mmol/L* ; 160 mg/dL*) are associated with genetic diseases of cholesterol metabolism. 
In China, where mean cholesterol is much lower than in the Western world, chronic hepatitis B virus infection is ubiquitous. Chronic carriers of hepatitis B, but not individuals with eradicated hepatitis B, have significantly lower total cholesterol than non-carriers, suggesting a cause-effect relationship. Inflammation and higher cholesterol levels are hypothesized to increase the risk of cardiovascular disease (CVD). Genetic diseases of cholesterol and lipid metabolism have been strongly associated with increased CVD.

Apolipoprotein A-I (Apo A-I)
The main protein component of HDL (high density lipoprotein, the so-called “good cholesterol”) accounts for approximately 65% of the total protein content of HDL. Apo A-I triggers the esterification or binding of free cholesterol with long-chain fatty acids. This is the form in which cholesterol can then be transported back to the liver, metabolized, and excreted in bile. Values of Apo A-I have been shown to decrease during infection.

APOLIPOPROTEIN B (APO B)
THE MAIN PROTEIN COMPONENT OF LDL (LOW DENSITY LIPOPROTEIN, THE SO-CALLED “BAD CHOLESTEROL”) ACCOUNTS FOR APPROXIMATELY 95% OF THE TOTAL PROTEIN CONTENT OF LDL. APO B IS NECESSARY FOR THE REACTION WITH LDL RECEPTORS IN THE LIVER AND ON CELL WALLS AND IS THUS INVOLVED IN TRANSPORTING CHOLESTEROL FROM THE LIVER TO THE CELLS. RECENTLY, THE MIND INSTITUTE FOUND THAT LOW VALUES OF APO B ARE ASSOCIATED WITH AUTISM, WITH THE LOWEST VALUES BEING FOUND IN LOW-FUNCTIONING AUTISM. LDL HAS BEEN FOUND TO HAVE PROTECTIVE EFFECTS AGAINST ENDOTOXINS FROM DEADLY STAPHYLOCOCCUS BACTERIA.

LIPOPROTEIN (A) (LP (A))
LP (A) IS A MODIFIED VERSION OF LDL CONTAINING APO B AND A UNIQUE PROTEIN, APOLIPOPROTEIN (A) LINKED BY A DISULFIDE BRIDGE. HIGH VALUES HAVE BEEN IMPLICATED AS A RISK FACTOR FOR CARDIOVASCULAR DISEASE, ALZHEIMER’S DISEASE, CROHN’S DISEASE, AND RHEUMATOID ARTHRITIS. LOW VALUES HAVE ALSO BEEN FOUND IN THOSE WITH AUTISM WHO HAVE HIGHER LEVELS OF APOLIPOPROTEIN E EPSILON-4 GENE VARIANTS THAT ARE ASSOCIATED WITH INCREASED RISK OF ALZHEIMER’S DISEASE. LIPOPROTEIN (A) IS BIOCHEMICALLY UNRELATED TO APOLIPOPROTEIN A.

HOMOCYSTEINE (HCY)
HOMOCYSTEINE (HCY) IS A SULFUR-CONTAINING AMINO ACID THAT IS CONVERTED BACK TO METHIONINE IN A CYCLE THAT REQUIRED B12 AND FOLIC ACID. ALTHOUGH THE ROLE OF HOMOCYSTEINE IN ATHEROSCLEROSIS IS STILL BEING STUDIED, HIGH HCY LEVELS SUGGEST SUPPLEMENTATION WITH FOLIC ACID AND VITAMIN B12 MAY BE PROTECTIVE. THE GENETIC DISORDER HOMOCYSTINURIA IS KNOWN TO CAUSE MASSIVE ATHEROSCLEROSIS IN YOUNGER PEOPLE, ALTHOUGH THE MECHANISM BY WHICH HOMOCYSTEINE PROMOTES NARROWING AND HARDENING OF ARTERIES IS UNKNOWN. ABNORMALLY HIGH VALUES HAVE BEEN REPORTED IN STROKE, CARDIOVASCULAR DISEASE, AND IN ALZHEIMER’S DISEASE. THE ADVANCED CHOLESTEROL PROFILE INCLUDES AN HCY LEVEL, WHICH IS USUALLY A SEPARATE BLOOD TEST.


The Advanced Cholesterol Profile uses FDA-approved diagnostic laboratory reagents, which assures quality results.

* SOME COUNTRIES (CANADA, EUROPE, MIDDLE EAST, AND OTHERS) REPORT CHOLESTEROL LEVELS USING MMOL/L WHILE THE U.S. AND LATIN AMERICA USE MG/DL.

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About the Author

William Shaw, PhD

William Shaw, PhD, is board certified in the fields of clinical chemistry and toxicology by the American Board of Clinical Chemistry. Before he founded The Great Plains Laboratory, Inc., Dr. Shaw worked for the Centers for Disease Control and Prevention (CDC), Children’s Mercy Hospital, University of Missouri at Kansas City School of Medicine, and Smith Kline Laboratories.