FAQ's about cholesterol, genetic disorders of cholesterol metabolism, and sonic hedgehog
Smith Lemli Opitz syndrome (SLOS) is a genetic disorder named after the physicians who discovered caused by a mutation that impairs or completely stops the last step of cholesterol production, leading to varying degrees of deficiency of cholesterol. The disease is homozygous recessive, meaning that a child needs to receive an abnormal gene from each parent or 2 abnormal genes to get the disease. It is estimated that carriers of the disease (people who only have one of the defective genes) may be as common as 1 in every 30 people with disease incidences on the order of 1 in 1,590 to 1 in 13,500. Some children with SLOS have no detectable cholesterol in their blood serum. Children or adults with SLOS have varying degrees of impairment that depend on the particular mutation in the gene that causes cholesterol deficiency of different degrees. Children with SLOS may present with specific facial dysmorphism and may have multiple congenital anomalies including cleft palate, congenital heart disease, genitourinary anomalies, and limb abnormalities. Important common features include short thumbs, severe photosensitivity, aggressive behavior, and atrioventricular septal defect. Cataracts are common in this disorder and any child with cataracts and autism should be tested for this disorder. They also manifest severe failure to thrive and mental retardation. However, some children with SLOS are only mildly affected in regard to physical malformations and autistic behavior may be their major abnormality.
The behavioral phenotype (appearance) of SLOS includes cognitive abilities ranging from borderline intellectual functioning to profound mental retardation, sensory hyper reactivity, irritability, language impairment, sleep cycle disturbance, self-injurious behavior, and autism spectrum behaviors. In one study, nearly 50% of children with SLOS met the DSM-IV criteria for autism. In another study, 86% of children with SLOS had an autistic spectrum disorder.
SLOS is confirmed by measurement of cholesterol and 7-dehydrocholesterol (7-DHC) by gas-chromatography mass spectrometry of blood serum. The gene defect leads to low total cholesterol and elevated amounts of the cholesterol precursors 7-DHC and 8-DHC. A strong clue that SLOS may be present in a child with autistic spectrum disorder is the presence of the second and third toes fused in the shape of the letter "Y". In some cases, the abnormality is so slight that it can only be detected by looking at the toes viewed from the bottom of the foot. However, some normal non-SLOS people may have this toe abnormality as well.
Cholesterol supplementation has allowed some patients to sleep through the night for the first time and others to overcome aberrant behaviors, to learn to walk, to speak for the first time, and to become responsive sociable family members. Other improvements found after cholesterol supplementation included increased sociability, learning to walk or run, fewer infections, reduced irritability and head banging, improved growth, and increased alertness and muscle tone. Those SLOS persons with speech said they felt much better. Some of the improvements occurred after only a few days of supplementation. In a pilot study by Tierney and Kelley (reported in ref. 3), cholesterol therapy reduced the mean ADI-R social domain score of five 4- to 5-yearold SLOS children from 18.2 ± 2.8 to 6.8 ± 1.8, where a normal score is 0 and scores above 10 are judged to be consistent with autism.
To determine if cholesterol deficiency is common in "ordinary" autism, Dr. Tierney and her associates involved in SLOS research investigated the incidence of biochemically diagnosed SLOS in blood samples from a group of subjects with autism spectrum disorder (ASD) from families in which more than one individual had ASD but were not suspected of having SLOS. Using the highly accurate gas chromatography/mass spectrometry, cholesterol, 7-DHC and its related molecules were quantified in 100 samples from subjects with ASD obtained from the Autism Genetic Resource Exchange (AGRE) specimen repository. Although no sample had 7-DHC values consistent with SLOS, 19 samples (19%) had total cholesterol levels lower than 100 mg/dl, values that are much lower than those found in normal children of the same age. In addition, this group found that cholesterol was low because of reduced production, not because of excess breakdown.
The Great Plains Laboratory found very similar results in a study of children with an autistic spectrum disorder. 17.5% of children with ASD had serum cholesterol values below 100 mg per dL blood serum. The Great Plains study did not select individuals with ASD from families with more than one case of ASD in the family. In addition, 57.5% had values below 160 mg/dL, a value below which abnormal behavior becomes more common.
This abnormality is common in Rett's syndrome, a genetic abnormality found predominantly in girls with autism who do not make purposeful use of their hands as frequently as other children with autism. A genetic test is now available for this disorder. These children might also benefit by checking their cholesterol.
The enzymatic method for cholesterol measurement based on cholesterol oxidase gives falsely high values for plasma cholesterol in samples from patients with SLOS. Both 7-DHC and 8-DHC contribute substantially to the test result, given that they are accepted substrates of cholesterol oxidase. All cholesterol methods making use of this enzyme (the methods used in virtually every laboratory in the world) are expected to give unreliable (falsely elevated) results with plasma samples from SLOS patients.
Yes, the cholesterol enzymatic method is reliable as long as 7-dehydrocholesterol is not present in high amounts. Thus, it can be used in any condition except in people with SLOS. If the child does not have severe physical defects and does not have a Y-shaped toe, SLOS is unlikely and the ordinary cholesterol test should be adequate. This enzymatic method is used at The Great Plains Laboratory.
Doses have varied from 50-150 mg cholesterol per kilogram (Kg) of body weight per day. For a 70 Kg adult with SLOS this would be a dose between 3500 mg to10,500 mg per day. The lower adult dose would be approximately equivalent to eating 14 eggs or 14 egg yolks (the yolk contains most of the cholesterol) a day. The lower dose appears to be as effective as the higher doses and thus, the lower dose is the most recommended dose for SLOS.
The concept of "good" and "bad" for dietary substances depends on the circumstances of the individual person. Much of the information that the public receives is oversimplified. To a person dying of thirst in the desert, any water is very good. To a person, who just drank two gallons of water on a dare, another glass of water might be fatal. The concept of good and bad cholesterol is similar to the water analogy.
A type of cholesterol that is associated with high density lipoproteins and helps to remove cholesterol from certain tissues was termed "good cholesterol" or HDL cholesterol (High Density Lipoprotein-associated cholesterol), while a type of cholesterol associated with low density lipoproteins and which transports cholesterol to tissues that require it was designated as "bad cholesterol" or LDL cholesterol (Low Density Lipoprotein-associated cholesterol). If, however, the tissues of a certain person have a significant overall deficiency of needed cholesterol, then both LDL and HDL cholesterol are good for that person. "Bad cholesterol" plays an important role in protecting the body from infection.
Cholesterol is not inherently "good" or "bad." The body will distribute supplemented cholesterol to the locations where it is needed the most. If the person has adequate amounts of cholesterol, cholesterol supplementation would not be needed for that person and might be harmful. If the person is deficient in cholesterol, cholesterol would be beneficial to tissues lacking it.
Yes, a research group at the University of California at Davis and the Mind Institute reported in 2007 that in a group of 69 children with autism there were significant reductions in peptide fragments from a lipoprotein called apolipoprotein B-100 that is associated with LDL and very low density lipoprotein (VLDL). Values were lowest in children with the most severe symptoms but were still somewhat low in high functioning children with autism. The same study showed that peptides corresponding to apolipoprotein A-IV were significantly lower in children with low-functioning compared to high-functioning autism. Another study found that brains of children with autism contained elevated amounts of Apolipoprotein E messenger ribonucleic acid (RNA), perhaps suggesting a more generalized dysregulation of apolipoprotein metabolism in autism.
LDL protects humans against infection. Deadly staphylococcus bacteria produce endotoxins that have the ability to kill human cells including red blood cells. LDL was found to protect human red blood cells from this toxic effect of endotoxin while HDL was not protective. A study at the University of Pittsburgh found that in young and middle aged men the total number of white blood cells and the number of various types of white blood cells were significantly lower in the men with LDL-cholesterol below 160 mg/dl than in men with LDL-cholesterol above 160 mg/l. Immune deficiency is a common symptom in individuals with SLOS. The rate of infections goes down rapidly after cholesterol supplementation to the people affected by SLOS syndrome.
Sonic cholesterol is obtained by extracting and purifying cholesterol from the wool of lambs. It has been carefully analyzed and has no detectable amounts of common pesticides, herbicides, or heavy metals such as lead or mercury. The identity of this nutrient has been confirmed by gas-chromatography-mass spectrometry.
"Sonic Cholesterol" will only be available to those individuals who obtain it through a physician who will evaluate the child, authorize appropriate testing, and evaluate the benefits to the child.
There are two sources of cholesterol: cholesterol in the diet and cholesterol that the body makes (endogenous cholesterol). Depending of the type of diet and various genetic factors, either dietary cholesterol or endogenous cholesterol may contribute the most to the body's cholesterol stores.
Cholesterol is a critical building block needed for all tissues and cells as a part of the cell membrane, the sack that holds the contents of the cells and determines what nutrients enter and leave. Cholesterol is especially high in the peripheral nerves and in the spinal cord and brain. A large portion of myelin, an insulating material that surrounds the nerve cells, is composed of cholesterol. Without this insulating material, the transmission of nerve signals that allow the nerve cells or neurons to communicate will be impaired. Cholesterol is concentrated in the brain more than any other organ.
In addition, cholesterol serves as the basic building block of many hormones called steroids. Sex steroids include testosterone and estrogens, while corticosteroids regulate sugar, fat, and protein metabolism and regulate the immune system. Aldosterone, another steroid, is an important regulator of salt balance. In addition, 7-dehydrocholesterol, the precursor of cholesterol, acts as the raw material for production of vitamin D in the skin.
In addition, cholesterol is needed for the function of a very important protein regulator of body and brain growth and development called sonic hedgehog and also regulates the action of the neurotransmitter serotonin. Probably many more functions of cholesterol will be discovered in the future.
Sonic hedgehog is a protein that is one of the members of a group of proteins called hedgehogs. The name "hedgehog" was given to these genes and the proteins they encode by researchers who found that fruit flies with severe genetic developmental abnormalities had bristles that stuck up like the hairs of a mammal called a hedgehog. Another hedgehog protein with even more profound effects on brain growth and development was given the name after the popular character in the videogame "Sonic Hedgehog". Mutations in the gene that controls the sonic hedgehog protein may be associated with holoprosencephaly (HPE), a condition in which there may be failure of the brain to form two separate lobes; in mild cases the children may only have hyperactivity and slightly abnormal facial features. It is possible that some children with autism might also have this abnormality. Of even greater interest is the possibility that the low cholesterol values in children with autism might lead to inactive forms of the protein called "sonic hedgehog" in the uterus or during early infant and childhood development since adequate cholesterol is essential to activate sonic hedgehog. In addition, fungal steroids and mercury are also likely to interfere in the function of this protein. Although cholesterol and fats are essential nutrients, there has been a health fad against these nutrients to such an extent that some pregnant women may not have had adequate amounts of nutrients to allow for normal developmental processes. Low cholesterol values were much more frequent in women who had premature babies and babies with microcephaly (small head).
Mental disorders of many types are associated with low cholesterol, including depression, bipolar disorder, anxiety, violent behavior, suicide, and Parkinson's disease. Early studies of therapies to reduce cholesterol to lower heart disease found that very low cholesterol increased death rates due to violence and suicide. Low cholesterol has been associated with greater incidence of HIV (AIDS) and other diseases. Cocaine addicts with low cholesterol had more difficulty overcoming their addiction than addicts with normal cholesterol. In addition, low cholesterol values have also been associated with increased cancer rates, manganese deficiency, celiac disease, hyperthyroidism, liver disease, malabsorption, and malnutrition. Evidence is available that cholesterol helps to support the function of the immune system. Many of these studies employ a cholesterol value below 160 mg/dL as abnormally low. However, most clinical laboratories do not even recognize that low values of cholesterol exist. Parents may have been told that the serum cholesterol value of their child was "normal" when it was really extremely low.
There may be. Ergosterol is the major steroid produced by Candida and other fungi. Research shows that ergosterol strongly inhibits the same enzyme, 3-hydroxysterol –delta-7-reductase, that is defective in SLOS disease. Thus, many of the harmful effects of Candida in autistic spectrum disorders might be mediated through interference in the production of human cholesterol. Many antifungal drugs inhibit the production of ergosterol by Candida species. In addition, many cases have been reported in which vitamin D and calcium were elevated after fungal infection and returned to normal after antifungal treatment. Since ergosterol blocks the conversion of 7-dehydrocholesterol to cholesterol, there will be increased conversion of 7-dehydrocholesterol to vitamin D instead. It is possible that some of the benefits of antifungal therapy in autism may be mediated by removing ergosterol to allow greater cholesterol production by human metabolism.
The transfer of cholesterol to the important developmental protein sonic hedgehog in order to activate it requires the action of a critical amino acid called cysteine in a certain specific part (called the active site) of the sonic hedgehog protein. Mercury specifically reacts with cysteine sulfhydryl groups, thus inactivating this important biochemical function. This same amino acid in sonic hedgehog plays a role in the introduction of another critical fatty acid called palmitic acid into a critical place in the sonic hedgehog molecule. Mercury would likely inhibit this function as well.
Cholesterol is excreted by the liver in fluid called bile. Bile is stored in the gall bladder and then released into the intestinal tract. Cholesterol in the intestinal tract may then be reabsorbed into the body or eliminated in the stool. Cholesterol may also be converted to bile salts which also enter the gall bladder and are released into the intestine. Bile salts are essential for the digestion and absorption of fats and fat soluble vitamins.
There are multiple reasons including reduced intake in the diet, reduced digestion and absorption, reduced synthesis by the tissues of the body, and increased elimination in the bile. Dysbiosis, insufficient production of digestive enzymes, and intestinal inflammation can lead to reduced cholesterol production. In addition, diarrhea causes any ingested cholesterol to pass too quickly through the intestine to be efficiently absorbed. In addition, the synthesis of cholesterol might be deficient because of genetic factors in any one of the 26 biochemical steps required for cholesterol synthesis in the body.
In addition, many vitamins and minerals, needed as cofactors for cholesterol synthesis may be deficient, slowing the rate of cholesterol synthesis. Finally, Candida and many other fungi produce ergosterol, a steroid similar to cholesterol which severely inhibits the final step in cholesterol synthesis. Mushrooms are also very high in ergosterol and may also reduce cholesterol synthesis. It is also possible that ergosterol inhibits one of the key enzymes in cholesterol metabolism (HMG Co A reductase) that is the rate limiting step in cholesterol production and the target of many statin drugs. Cholesterol inhibits this enzyme by a negative feedback mechanism. Ergosterol has a structure so similar to cholesterol that it might also have a similar negative feedback effect. Thus, Candida infection for long periods of time might lead to low cholesterol values, simulating the SLOS disease.
Diarrhea accelerates the elimination of any cholesterol excreted in the bile, preventing it from being recycled. In addition, many children with autism are deficient in sulfur containing amino acids. One of these is taurine, a critical amino acid that combines with cholesterol derivatives to form bile salts. If bile salts are not formed in adequate quantities, increased amounts of cholesterol derivatives will be secreted into the bile. Ordinarily bile salts are recycled. They are secreted into the intestine and then later reabsorbed. When cholesterol cannot be converted into bile salts, cholesterol will be secreted into the intestine and a significant fraction may not be able to be reabsorbed.
Parents of children with autism often report abnormal color of their children's stool. The stool is frequently described as clay colored or white or lightly colored. The brown color in normal stool is due to bile pigments. Light or uncolored stools probably indicate an inadequate flow of bile possibly due to inadequate stimulation of bile release from the gall bladder due to deficient taurine. Many parents report the presence of "sand" in their child's stool. This "sand" is probably due to the presence of insoluble bile salts in the stool. The amount of "sand" is reported to increase dramatically after secretin infusions probably because secretin stimulates bile release. Bile salts containing taurine do not form this "sand" because they are more soluble.
In addition, lack of bile salts markedly reduces the absorption of cholesterol and other fats.
The Great Plains Laboratory have a special cholesterol-related panel that includes total cholesterol, apolipoprotein A-1, apolipoprotein B, Lipoprotein (a), and homocysteine. This panel will help to determine whether cholesterol deficiency or cholesterol transport is present. All of the tests use FDA-approved reagent kits.
Apolipoprotein A-I is the main protein component of HDL (high density lipoprotein) and accounts for approximately 65% of the total protein content of HDL. Apolipoprotein A-I activates lecithin cholesterol acyltransferase which catalyses the esterification of cholesterol. The resulting esterified cholesterol can then be transported to the liver, metabolized and excreted.
Apolipoprotein B is the main protein component of LDL (low density lipoprotein) and accounts for approx. 95% of the total protein content of LDL. Apolipoprotein 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 vessel cell. Low values are associated with autism with the lowest values being found in low-functioning autism.
Lipoprotein (a) consists of two components, the low-density lipoprotein (LDL) and a glycoprotein, which are 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 been found in autism. Lipoprotein (a) is biochemically unrelated to lipoprotein A.
Homocysteine is a sulfur containing amino acid that can be converted to methionine by methionine synthetase or by betaine methyl transferase. The role of homocysteine in atherosclerosis gained attention after finding massive atherosclerosis in young people with the genetic disorder homocystinuria. Methionine synthetase requires the folic acid derivative 5-methyl tetrahydrofolate. Abnormally high values have been reported in stroke, cardiovascular disease, and in Alzheimer's disease but both high and low values have been associated with autism.
Cholesterol values only change slightly after meals. The main reason for fasting before blood lipid profiles is that the blood fat triglycerides changes rapidly after meals. Triglycerides are included in other cholesterol panels but not in the autism lipid panel of The Great Plains Laboratory. We recommend a 3-hour fast after meals before collection of serum for this panel to minimize test interferences due to fat particles (lipemia). In addition, we recommend that a small meal low in fat be used prior to collection of the cholesterol profile. An apple or other fruits low in fat might be an ideal meal before sample collection. A high fat diet containing bacon, eggs, or whole milk should be avoided. There may be occasional interferences with the 3-hour fast. Alternatively, an overnight fast can be done. A detailed study on fat changes after meals showed that mean cholesterol values collected after a fatty meal containing high cholesterol egg yolks(33 % fat, 33% protein, 33% carbohydrate) were very slightly lower than those before the meal, perhaps because the dietary cholesterol inhibits the production of cholesterol by the body. The largest increase in cholesterol reported after a fatty meal was approximately 6% with some people having an equivalent decrease in cholesterol, and others with no change. Samples collected after an overnight fast rarely have significant interferences but the inconvenience and stress of fasting in an impaired child must be weighed against the small cholesterol changes.
Even if sonic hedgehog is completely activated with cholesterol, it must be secreted and react with receptors for the sonic hedgehog. If such receptors are abnormal or external factors interfere with sonic hedgehog binding to its receptors, the individual may still not respond to functional hedgehog, perhaps resulting in impaired development and/or autistic disorders.
In addition, SLOS is only one of the 26 steps in cholesterol synthesis. Mutations in any of these other genes might also be expected to result in developmental and/or autistic spectrum disorders. Any abnormality that alters the lipoproteins that transport cholesterol or accelerate its elimination might also have a profound developmental effect on the growing fetus. Dr. Kelly, an SLOS researcher at John Hopkins University states:
"Clinical and basic research on prenatal cholesterol nutrition in SLOS and various animal model systems has delineated a previously unrecognized system for the delivery of low-density lipoprotein cholesterol from the mother to the developing embryo.
The many discoveries engendered by these experiments of nature argue that there are heretofore unrecognized beneficial effects of cholesterol, especially in children, and that we should consider very carefully possible adverse effects that the popular war against cholesterol may have on the prenatal and postnatal development of children"
Cholesterol and autistic spectrum disorders
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- Sikora DM, Pettit-Kekel K, Penfield J, Merkens LS, Steiner RD. The near universal presence of autism spectrum disorders in children with Smith-Lemli-Opitz syndrome. Am J Med Genet A. 2006 Jul 15;140(14):1511-8.
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- BA Corbett, AB Kantor, H Schulman, WL Walker, L Lit, P Ashwood, DM Rocke and FR Sharp. A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins.
Low cholesterol association with depression and/or suicide
- Modai I et al. Serum cholesterol levels and suicidal tendencies in psychiatric inpatients. J Clin Psychiatry. 1994 Jun;55(6):252-4.
- Cassidy F, Carroll BJ. Hypocholesterolemia during mixed manic episodes. Eur Arch Psychiatry Clin Neurosci. 2002 Jun;252(3):110-4.
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Cholesterol and sonic hedgehog
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- Roessler E, Ward DE, Gaudenz K, Belloni E, Scherer SW, Donnai D, Siegel-Bartelt J, Tsui LC, Muenke M (1997) Cytogenetic rearrangements involving the loss of the Sonic Hedgehog gene at 7q36 cause holoprosencephaly. Hum Genet 100:172–181
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Low cholesterol and increased infection or impaired immunity
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- Leardi S, Altilia F, Delmonaco S, et al. Blood levels of cholesterol and postoperative septic complications. Ann Ital Chir 2001; 71: 233-237.
- Crook MA, Velauthar U, Moran L, Griffiths W. Hypocholesterolaemia in a hospital population. Ann Clin Biochem 1999; 36: 613-616.
- Read TE, Harris HW, Grunfeld C, et al. The protective effect of serum lipoproteins against bacterial lipopolysaccharide. Eur Heart J 1993; 14(suppl K): 125-129.
- Bonville DA, Parker TS, Levine DM, et al. The relationships of hypocholesterolemia to cytokine concentrations and mortality in critically ill patients with systemic inflammatory response syndrome. Surg Infect (Larchmt). 2004; 5: 39-49.
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- Uffe Ravnskov. High Cholesterol May Protect Against Infections and Atherosclerosis. Quart J Med 2003; 96: 927-34.
Low cholesterol and impaired or criminal behavior
- Jian Zhang1, Matthew F. Muldoon, Robert E. McKeown, and Steven P. Cuffe. Association of Serum Cholesterol and History of School Suspension among School-age Children and Adolescents in the United States. American Journal of Epidemiology Vol. 161, No. 7
- Zhang J, Muldoon MF, McKeown RE. Serum cholesterol concentrations are associated with visuomotor speed in men: findings from the Third National Health and Nutrition Examination Survey, 1988–1994. Am J Clin Nutr 2004; 80:291–8.
- Golomb BA. Cholesterol and violence: is there a connection? Ann Intern Med 1998;128:478–87.
- Golomb BA, Stattin H, Mednick S. Low cholesterol and violent crime. J Psychiatr Res 2000;34:301–9.
- Kaplan JR, Shively CA, Fontenot MB, et al. Demonstration of an association among dietary cholesterol, central serotonergic activity, and social behavior in monkeys. Psychosom Med 1994;56:479–84.
- Repo-Tiihomen E, Halonen P, Tiihonen J, et al. Total serum cholesterol level, violent criminal offences, suicidal behavior, mortality and the appearance of conduct disorder in Finnish male criminal offenders with antisocial personality disorder. Eur Arch Psychiatry Clin Neurosci 2002; 252:8–11.
- Muldoon MF, Barger SD, Ryan CM, et al. Effects of lovastatin on cognitive function and psychological well-being. Am J Med 2000;108:538–46.
- Laure Buydens-Branchey, and Marc Branchey, Association Between Low Plasma Levels of Cholesterol and Relapse in Cocaine Addicts Psychosomatic Medicine 65:86-91 (2003)
Cancer and low cholesterol
- Alsheikh-Ali et al.Effect of the Magnitude of Lipid Lowering on Risk of Elevated Liver Enzymes, Rhabdomyolysis, and Cancer: Insights From Large Randomized Statin -- Journal of the American College of Cardiology Trials 50 (5): 409-418, 2007
- Isles CG, Hole DJ, Gillis CR, Hawthorne VM, Lever AF Plasma cholesterol, coronary heart disease, and cancer in the Renfrew and Paisley survey. BMJ.1989 Apr 8;298(6678):920-4.
Premature birth or abnormal development linked with low cholesterol or abnormal cholesterol metabolism
- Forbes D. Porter. Malformation syndromes due to inborn errors of cholesterol synthesis.J. Clin. Invest. 110:715–724 (2002)
- Robin J. Edison, Kate Berg, Alan Remaley, Richard Kelley, Charles Rotimi, Roger E. Stevenson, and Maximilian Muenke, Adverse Birth Outcome Among Mothers With Low Serum Cholesterol. Pediatrics 2007; 120: 723-733.
Importance of cholesterol in brain function
- Ingemar Björkhem and Steve Meaney. Brain Cholesterol: Long Secret Life Behind a Barrier. Arterioscler. Thromb. Vasc. Biol. 2004;24;806-815
Homocysteine and autism
- Sergiu P. Pas¸ Bogdan Nemes¸ Laurian Vlase, Cristina E. Gagyi, Eleonora Dronca, Andrei C. Miu, Maria Dronca. High levels of homocysteine and low serum paraoxonase 1 arylesterase activity in children with autism. Life Sciences 78:2244-2248,2006.
- James, S.J., Cutler, P., Melnyk, S., Jernigan, S., Janak, L., Gaylor, D.W., Neubrander, J.A., 2004. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. The American Journal of Clinical Nutrition 80 (6), 1611– 1617.
Vitamin D abnormalities in yeast/fungal infections
- Wang IK, Shen TY, Lee KF, Chang HY, Lin CL, Chuang FR. Hypercalcemia and elevated serum 1.25-dihydroxyvitamin D in an end-stage renal disease patient with pulmonary cryptococcosis. Ren Fail. 2004 May;26(3):333-8.
- ALI, M. Y. MD; GOPAL, K. V. LLERENA, L. A. MD; TAYLOR, H. C. Hypercalcemia Associated with Infection by Cryptococcus neoformans and Coccidioides immitis. American Journal of the Medical Sciences. 318(6):419, December 1999.
- Spindel SJ, Hamill RJ, Georghiou PR, Lacke CE, Green LK, Mallette LE.Case report: vitamin D-mediated hypercalcemia in fungal infections. Am J Med Sci. 1995 Aug;310(2):71-6.
Effect of meals on cholesterol values
- Jeffrey S. Cohn, Judith R. McNamara, Susan D. Cohn, Jose M. Ordovas, and Ernst J. Schaefer. Postprandial plasma lipoprotein changes in human subjects of different ages. Journal of Lipid Research Volume 29, 1988 pgs 469-478.