Cholesterol and Statins: Part I

Cholesterol & Statins (Part I)

by Yusuf M. Saleeby, MD

to be published in American Fitness magazine (Jan/Feb 2013)

Today when one hears the word “cholesterol” it conjures up thoughts of “something bad”.  Whether we hear about a cholesterol level over 200 from a neighbor, or one of many TV shows preaching the avoidance of cholesterol rich foods, cholesterol always seems to drum up connotations of bad, evil or unhealthy.  This two part series will dispel the myths and urban legends about cholesterol and expand the reader’s knowledge of this rather important steroid compound.  Part II of this series will encompass the atherogenic (plaque forming properties of oxidized native LDL-Cholesterol) and what measures can be taken to minimize the risk of stroke and heart attack specifically focusing on a class of medication call statin drugs.

Although Cholesterol as a solid fatty substance was first isolated a half-century before, recognition was given to the scientist who named it in the early 1800’s.  A French chemist named Michel Eugène Chevreul, while studying bile acids and animal fats, christened this new compound.  He derived the name we use today from two Greek words Chole (of the bile) and stereos (solid) adding the –ol usually used to denote an alcohol component [(3β)-cholest-5-en-3-ol is the chemist’s nomenclature for cholesterol] (Olson, 1998).

Cholesterol is essential to mammalian cells as a major component in cell membranes.  This steroid molecule allows for membrane permeability and the flexibility and fluidity integral to our cells.  Additionally, cholesterol is the substrate or building block of other essential biologic end-products, namely the steroid hormones (testosterone, progesterone, estrogens and DHEA to name a few), the bile acids that help with digestion, and as a precursor substrate to the important vitamin/hormone vitamin D (Hanukogul, 1992). 

Essential to life and proper bodily functions as we know it cholesterol is a double edged sword and has in fact a dark side.  Too much either by dietary intake or endogenous production can cause damage to arteries and lead to cardiovascular disease.  Cardiovascular events such as acute myocardial infarction (heart attack) and cerebral vascular accident (stroke) are the consequence in part to the narrowing of blood carrying vessels to the heart and brain respectively.  This narrowing occurs in great part to the formation of plaques rich in cholesterol that line the lumen of arterial vessels.  After a period of time, growth and maturation these plaques “clog” those vessels.

Breaking down cholesterol into further sub-components sometimes adds to the confusion of the part cholesterol plays in health.  For example there are two major subcomponents of total serum cholesterol called low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C).  One is often referred to as the “bad cholesterol.”  Because LDL-C is responsible for building up on artery walls when there is too much in circulation it is referred to as bad.  Produced in the liver and transported to cells, LDL is rather harmless until levels in the serum get too high or the native-LDL is oxidized by free-radicals and becomes atherosclerogenic (that which forms plaques) (Rosenson, 2010).  On the other hand HDL-C is called the “good cholesterol” in part because the smaller subcomponents are themselves protective and also because it’s main function is to transports cholesterol away from the cells and back to the liver for recycling or disposal.  The higher levels you have of HDL-C in your serum, the lower your chances for cardiovascular disease and its sequelae (Brunzell, 2008; Durrington, 2003).  A caveat recently realized is that lowering LDL-C is not the end-all-be-all of lipid management.  It turns out there are other players in plaque forming dyslipidemia such as triglycerides (TG), apolipoprotein B (apoB), and others that may be as important (or more so) in controlling cardiovascular disease (Miller, 2009; Sierra-Johnson, 2009; Handrean, 2011).  Apolipoproteins are proteins that bind lipids (including cholesterol) making the non-water-soluble lipids easier for transport through the water-based blood and lymphatic systems (Saito, 2004).

The Good, Bad and Ugly of cholesterol. 

Firstly let us discuss the body’s requirements and utilization of cholesterol, that we will call the “good”; then we can discuss how some types of cholesterol can hurt our cardiovascular system, that discussion we will call the “bad.”  And finally, we will reserve the discussion of controlling elevated levels of cholesterol with statin drugs (HMG-coA-reductase inhibitors) and by other means as the “ugly” aspect of our two part series.  Ugly you may ask?  Well there is much controversy and debate on how to lower, what to lower and how far or aggressive we need to get in lowering cholesterol.  There are schools of thought about lowering LDL and others on raising HDL.  Then there are the lipoproteins and triglycerides and their role in this game.

From its formation, cholesterol is made predominately in the liver.  A complex 37-stage enzymatic process has to occur to derive cholesterol from the base substrate substances of acetyl coenzyme A.  An important enzyme called 3-hydroxy-3-methylglutaryl CoA reductase (or HMG-CoA reductase) is critical for the formation of cholesterol in the liver.  This concept is important for our discussion on statin drug therapy.  Statin drugs are effective at lowering cholesterol as they inhibit this crucial enzyme. 

Production of cholesterol is in full force at night while we sleep.  Our bodies produce up to 1000 mg of cholesterol per day on average, while the typical 70 Kg (~150lb) person contains about 35 grams of cholesterol by weight.  Our diet, even the standard American high-fat diet, provides us with only between 200 and 300 mg of cholesterol per day.  So our bodies make more cholesterol than what we can possibly take in orally.  This becomes an important fact in how we can effectively treat elevated cholesterol, and in a way reveals the true etiology of dyslipidemia.  It shows the importance of genetics versus environment.  [Hint:  Dietary restriction of high cholesterol foods is a poor way of controlling dyslipidemia.] can be used in a side bar 

Cholesterol is recycled, first excreted by the liver, making a round trip to our cells and back via LDL-C and HDL-C, and then reabsorbed back into the liver to be excreted as bile acid.  This bile is stored in the gallbladder until needed to help digest ingested foods that contain fats and oils.  Approximately 50% of the excreted bile acids are then reabsorbed in the small intestines and returned into circulation.  These facts are again important when we consider how to manager elevated LDL-C.  The use of drugs that inhibit bile acid reabsorption can in theory work, as can phytosteroils from some plants that mimic bile acids.  Phytosteroils are preferentially secreted back into the gut, thus interfering with normal recirculating of bile acids.

Cholesterol is responsible for the absorption of critically important nutrients via the digestive system as the component of bile acids in bile.  The body’s requirements for vitamins A, D, E and K (all fat soluble) are linked to how well they are absorbed in our intestines when solubilized by bile.  Additionally, fats necessary for good health and energy production also require bile for intestinal absorption.  Cholesterol as a metabolic building block is necessary for the synthesis of vitamin D, and our steroid hormones (sex hormones) as well as those of the adrenal gland such as cortisol and aldosterone (Hanukogul, 1992).

So why all the fear about high levels of cholesterol?

Well it goes back to research showing a strong link between elevated total cholesterol and LDL-C specifically and heart disease.  While not the only major risk factor for coronary artery disease, it remains one of intense focus and scrutiny.  Researchers and drug companies hustled into the arena of determining how to control LDL and how best to drive the numbers down in the masses to relieve our industrialized society of the burden of sudden death by heart attack.  Reduce LDL and total cholesterol and the thinking was increased longevity and a better quality of life.

To put things into perspective if too much LDL is abound and not being utilized by the cells in a productive way, they eventually become oxidized as the lazy loiterers they are and start doing bad things to our artery wall lining.  The process is assisted by macrophages (part of our body’s immune system) which takes up this oxidized-LDL and becomes engorged forming what we refer to as “foam cells”.  These foam cells are trapped in the walls of blood vessels and when they mature over time, become atherosclerotic plaques (Weingärtner, 2010; Tymoczko, 2002).  They form on arterial walls of our carotid artery, our larger vessels and even the smaller coronary artery vessels. There may be other factors as to why they develop here versus there and it has been theorized that micro-trauma, inflammation or even infectious organisms may play a role.  Non-the-less, as these plaques get larger, they narrow the lumen of the arteries and thus set up a situation for bottlenecking of blood corpuscles passing through.  Add a few clotted platelets and presto, you have a recipe for disaster, a clotted artery unable to provide critical oxygenated blood to distal tissues (myocardium in the case of a heart attack and brain tissue in the case of a thrombotic stroke).  Without the oxygenated blood servicing our cells there is injury and eventual death of those cells which lead to one clutching their chest in pain or loosing neurological function.

To the rescue comes HDL-C, remember this is the good cholesterol.  This high density cholesterol and its lipoproteins are given credit for removing excess cholesterol from peripheral tissues and transporting them back to the liver.  This process known as reverse cholesterol transport is one of the chief functions of this beneficial type of cholesterol thus lowering risk for coronary disease (Gordon, 1989).  So what would do our bodies better, lowering LDL-C or raising HDL-C?  That argument continues.

Why the big focus on total cholesterol and LDL-Cholesterol? 

To answer that question one has to consider a few landmark studies in lipids related to plaques in the aorta.  The famous pathologist Dr. Rudolf Virchow noted back in 1856 lipid like plaques on arteries, this was followed by a celebrated study by the Russian scientist Dr. Nikolai Anitschkow in 1913, who fed rabbits high cholesterol diets (Virchow,1856, Steinberg, 2004).  Since then these high-lipid diet studies have been repeated in almost every animal model know.  LDL-cholesterol and it’s link to atherogenesis was what won Drs. Joseph Goldstein and Michael Brown a Nobel prize in medicine in 1985 for their appreciation of the LCL-C and heart disease connection (Goldstein,1973).  From that point, there was an explosion of research showing elevated cholesterol either by overconsumption of bad dietary fats or by poor genes.  Either way there was a link to heart disease (Steinberg, 2004-2006). 

In 1984 one of the first large scale double-blinded interventional trials called the Coronary Primary Prevention Trial (LRC-CPPT) demonstrated that a decrease in serum cholesterol, by a sequestrant drug called cholestyramine, significantly reduced heart attacks (JAMA, 1984).  From there pharmaceutical companies started their marathon race toward producing some of the most prescribed therapeutics in history that reduces cholesterol.  That will all be discussed in Part II of this series.  Despite the fact that there are other risk factors for heart disease and heart attack/stroke, the focus currently remains fervently on LDL-C and the development of statin drugs for lowering cholesterol. 

Other risk factors may actually be of greater importance to the health of the heart and brain, notably among them are family history/genetics, gender, race, obesity, diabetes, tobacco abuse, hypertension, hypertriglyceridemia, elevated homocysteine, inflammation, chronic kidney disease, sedentary lifestyle, Lp(a), fibrinogen, and elevate Lipoprotein B (Watts, 2011).  Of these it is currently though that the top three risk factors for heart disease and stroke are diabetes mellitus (DM), hypertension (HTN) and tobacco smoking and not LCL-C elevation.  In a 2002 cross-sectional analysis of the Copenhagen City Heart Study lipid disorder as a cardiac risk factor was ranked fifth and sixth overall in importance given one’s gender (Schnohr, 2002).

References:

Olson RE., "Discovery of the lipoproteins, their role in fat transport and their significance as risk factors", J. Nutr. 1998, 128 (2 Suppl): 439S–443S.

Hanukoglu I., "Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis.". J Steroid Biochem Mol Biol  1992, 43 (8): 779-804.

Rosenson RS, “Lp-PLA2 and risk of atherosclerotic vascular disease”, Lancet, 2010, Vol. 375, Issue 9725, Pages 1498-1500.

Brunzell JD, Davidson M, Furberg CD, Goldberg RB, Howard BV, Stein JH, Witztum. "Lipoprotein management in patients with cardiometabolic risk: consensus statement from the American Diabetes Association and the American College of Cardiology Foundation". Diabetes Care 2008, 31 (4): 811–22.

Durrington P., "Dyslipidaemia". Lancet 2003, 362 (9385): 717–31.

Miller M, “Dyslipidemia and cardiovascular risk: the importance of early prevention”, QJM (2009) 102 (9): 657-667.

Sierra-Johnson J et. al.,”Concentration of apolipoprotein B is comparable with the apolipoprotein B/apolipoprotein A-I ratio and better than routine clinical lipid measurements in predicting coronary heart disease mortality: findings from a multi-ethnic US population”, Eur Heart J , 2009, 30 (6): 710-717.

Handrean, S., et. al., “Apolipoprotein B100 is a better treatment target than calculated LDL and non-HDL cholesterol in statin-treated patients”, Ann Clin Biochem November 2011 vol. 48 no. 6566-6571.

Saito H, Lund-Katz S, Phillips MC. "Contributions of domain structure and lipid interaction to the functionality of exchangeable human apolipoproteins". Prog. Lipid Res. 2004, 43 (4): 350–80.

Weingärtner O, et. al. (2010). Federici, Massimo. ed. "The relationships of markers of cholesterol homeostasis with carotid intima-media thickness".

Tymoczko, John L.; et, al., (2002). Biochemistry. San Francisco: W.H. Freeman. pp. 726–727.

Gordon DJ, et. al., "High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies". Circulation 1989, 79 (1): 8–15.

Virchow, Rudolf (1856). "Gesammelte Abhandlungen zur wissenschaftlichen Medizin". Germany: Staatsdruckerei Frankfurt. Phlogose und Thrombose im Gefäßsystem. (German)

Steinberg D., “Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy: part I”. J Lipid Res. 2004 Sep;45(9):1583-1593.

Steinberg D.,  "Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy, part V: the discovery of the statins and the end of the controversy". J. Lipid Res. 2006, 47 (7): 1339–51.

Goldstein JL, Brown MS, "Familial Hypercholesterolemia: Identification of a Defect in the Regulation of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Activity Associated with Overproduction of Cholesterol". Proc. Natl. Acad. Sci. USA, 1973, 70 (10): 2804–2808.

The Lipid Research Clinics Coronary Primary Prevention Trial Results: I. Reduction in Incidence of Coronary Heart Disease. JAMA. 1984;251(3):351-364.

Watts, G., “Republished review: Triglycerides and atherogenic dyslipidaemia: extending treatment beyond statins in the high-risk cardiovascular patient”, Postgrad Med J 2011;87:776-782.

Schnohr, et. al., “Coronary heart disease risk factors ranked by importance for the individual and community: a 21 year follow-up of 12 000 men and women from The Copenhagen City Heart Study”, European Heart Journal (2002) 23, 620–626.

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Yusuf (JP) Saleeby, MD is medical director of WellnessOne and WellnessFirst which offer extensive and advanced cardiovascular and stroke biomarker and genetic analysis, including lipid subtypes, Lp(a), HDL₂ and HDL₃, LDL_1-4, ApoB, NT-proBNP, and  the 4q25, 9p21, ApoE & KIF6 genotypes, and other evaluations.  He is a regular contributor to American Fitness and is on the medical advisory board.  He can be reached for comment at ymsaleeby@gmail.com.

Advanced Testing offered at WellnessOne

ApoE, Diet, CADz, Alzheimer's Dz: Why you should get tested.

ApoE, diet, heart disease risk and Alzheimer’s Disease:

A reason to get tested

Edited material reviewed by JP Saleeby, MD

The Apolipoprotein E (APOE) gene located on chromosome 19, is the major genetic source of the common forms of late-onset Alzheimer disease (Alzheimer's disease), cardiovascular disease and matching the ‘’best dietary recommendations’’ for individuals. This gene is polymorphic and has three allelic isoforms or variants (ApoE2, ApoE3, and ApoE4) and five common genotypes (2/3, 3/3, 2/4, 3/4, and 4/4).  The Apolipoproteins themselves are what is transcribed from the gene and they are 299 amino acids long.  The protein ApoE is an Apolipoprotein class found in chylomicrons and Intermediate-Density Lipoproteins (IDLs) responsible for normal catabolism of triglyceride-rich lipoprotein constituents.  Besides lipid transport importance, there is function with immunoregulation and cognition.

Making sense out of these letters.

For the sake of nomenclature ApoE4 (APOE4)  is the protein (apolipoprotein E4) while Apoε4 is the allele (gene designation, sometimes also noted as ApoE4 allele).

Regarding the genotypes, 7% of the population has E2 (E2/E2) and these individuals may clear dietary fat slowly and be at greater risk for CADz.  94.4% have the E2/E2 pattern.

E3 is called neutral or “native’’ and the vast majority of the population (79%) have this type of allele, (E3/E3).  This genotype is by far the most common.

The ApoE4 allele is found in about 14% of the population.

ApoE and  Alzheimers Disease.

ApoE4 allele increases the risk and decreases the average age of dementia onset in a dose-related fashion, such that the risk of Alzheimer disease is lowest in patients with the 3/3 genotype, higher for the 3/4 genotype, and highest for the 4/4 genotype.  Those with 4/4 have a 10 to 30 times the risk for developing late onset AD.  The ApoE2 allele lowers the risk of Alzheimer disease (AD).

However, ApoE4 accounts for only part of the genetic risk for Alzheimer disease. A family history of dementia, regardless of ApoE4 status, can also increase the risk of developing the disorder. Specifically, persons with a first-degree relative with dementia have a 10-30% increased risk of developing Alzheimer disease.

Of note, an investigation in an elderly Swedish population reported that a family history of dementia was associated with an increased risk of dementia and Alzheimer disease only among ApoE4 carriers, suggesting that there might be other familial genetic or environmental factors active in the presence of ApoE4.

The underlying mechanism through which ApoE influences Alzheimer disease risk has not yet been determined. Scientists have explored several possibilities, including the idea that ApoE may play a role in cholesterol transport, neuronal integrity, and amyloid deposition.

Additional studies revealing the true mechanism could eventually lead to more specific treatments for Alzheimer disease. Indeed, studies of asymptomatic ApoE4 carriers show that these persons are more likely to display subtle abnormalities on brain scans, such as positron emission tomography (PET) or magnetic resonance imaging (MRI) scans.  Although 40-65% of AD patients have at least one copy of the 4 allele, ApoE4 is not a determinant of the disease - at least a third of patients with AD are ApoE4 negative and some ApoE4 homozygotes never develop the disease.  ApoE(2,3) is the lowest risk, but interestingly ApoE(2,4) and ApoE(3,3) carry the same rate of AD.

Thus, combining information on ApoE4 carrier status with other informative biological-marker data is a promising research strategy for detecting individuals who might be candidates for Alzheimer disease prevention strategies.

Despite concerns about genetic testing, studies of individuals who have learned that they are ApoE4 carriers have not demonstrated higher rates of anxiety or depression. Rather, some ApoE4 carriers are motivated to adapt a healthier lifestyle to maximize brain health. ^[1-9]

In industrialized countries, cardiovascular diseases are widespread and are amongst the most frequent causes of death.  In particular, increased cholesterol and triglyceride values in the blood are risk factors in this case. Along with an unhealthy lifestyle, genetic changes may also cause an increase in blood lipid levels.  Apolipoprotein E (ApoE) is, for example, also affected by such changes.  In the homozygotic presentation, the ApoE2 allele (E2/E2) is associated with type III hyperlipoproteinaemia.  This clinical picture leads to an increased risk of arteriosclerosis.  Testing for the presence of the ApoE2 allele can support the diagnosis of type III hyperlipoproteinaemia and should be performed if the disease is suspected.  Even in the case of ApoE4 allele carriers, there can be after-effects on health due to disrupted lipid metabolism. Carriers of this allele are exposed, for example, to an increased risk of coronary heart disease. Therefore, for patients with increased cholesterol and triglyceride values, gene typing is likewise recommended in order to clarify any genetic causes.¹⁰

The highest ApoE3 frequencies are found in populations with a long-established agricultural economy (Gerdes et al. 1996) such as those of the Mediterranean basin or East Asia.  It is possible that the metabolic properties of the E3 isoform proved to be particularly advantageous in the transition from food collection to food production.  At present, the frequency of ApoE4 within all the major human groups remains higher in those populations…where an economy of foraging still exists, or food supply is now or has until recently been scarce, sporadically available or qualitatively poor. Under these environmental conditions, carrying the ApoE4 could be still useful. For example, most of these populations have lower plasma cholesterol levels than those observed among Western countries. Since ApoE4 is associated with both a higher absorption of cholesterol at intestinal level, and higher plasma cholesterol levels, individuals carrying it would be favored because this allele could help in rebalancing cholesterol levels which would otherwise be too low (Scacchi et al. 1997).  However, with a Western (American) diet, this type of allele expression has proven detrimental to our health with regard to cardiovascular disease and dementia.

Hopefully this just means one should eat primal, who really wants to eat a low cholesterol diet. It is clearly a gene-environment interaction that leads to high levels of heart disease (CAD) and Alzheimer’s (AD) for ApoE4s.  Because the developing world (3^rd world countries) have more E4s yet far less CAD & AD, there is certainly an environmental component to disease expression.¹¹

How does Alcohol play into things?

The effect of alcohol drinking on LDL-cholesterol concentrations is unclear. The reported variability may be due to interactions between genetic factors and alcohol intake.  A study was conducted to examine Apolipoprotein E gene (ApoE) locus association between alcohol drinking and LDL cholesterol.  The study was a cross-sectional design in a healthy population-based sample of 1014 men and 1133 women from the Framingham Offspring Study.

In male nondrinkers, LDL cholesterol was not significantly different across ApoE allele groups [APOE*E2 (E2), APOE*E3 (E3), and APOE*E4(E4)].  However, in male drinkers, differences were observed; those with the E2 allele had the lowest concentrations. LDL cholesterol in men with the E2 allele was significantly lower in drinkers than in nondrinkers but was significantly higher in drinkers than in nondrinkers in men with the E4 allele. This ApoE alcohol interaction remained significant after age, body mass index, smoking status, and fat and energy intakes were controlled for.  In women, the expected effect of ApoE alleles on LDL cholesterol occurred in both drinkers and nondrinkers.  Multiple linear regression models showed a negative association between alcohol and LDL cholesterol in men with the E2 allele but a positive association in men with the E4 allele. No significant associations were observed in men or women with the E3 allele.  Therefore, in men, the effects of alcohol intake on LDL cholesterol are modulated in part by variability at the ApoE locus.  So if a male with an ApoE2 allele drinks alcohol it can lower the LDL.  If however, he has the ApoE4 it will raise LDL-C.  That is likely the reason we see lower cholesterol levels in some men who drink heavily.  Unless you know which allele you possess, drinking alcoholic beverages can be a coin toss.¹²

How can determining your ApoE gene type help with weight loss?

Overall, carriers of the ApoE2 allele had lower LDL-cholesterol concentrations and a tendency to higher triglycerides (TGs) concentrations relative to carriers of the ApoE3 and ApoE4 alleles. In addition, there was a positive association between dietary sucrose (6–7% of the total energy intake) and plasma TG concentrations only in carriers of the ApoE2 allele.

Although it is difficult to speculate about the mechanisms behind these effects, one can envision several possibilities. First, E2 allele carriers may have a compromised clearance system for TG-rich lipoproteins, thus they should avoid high fat diets and high sugar (carb) diets. Even a modestly increased VLDL production in response to sucrose could result in an increased plasma TG concentration. Alternatively, in addition to affecting uptake of TG-containing remnant particles, the ApoE polymorphism may play a role in the intrahepatic synthesis and catabolism of TG-rich lipoproteins.  Those with the ApoE4 genotype, having already mentioned this as being the “thrifty gene” and their inability to process cholesterol very well, are likely to benefit from a low cholesterol and dietary fat diet.  This is helpful when directing patients to follow a particular type of diet or weight loss program.  Depending on your ApoE allele type there may be better weight loss and weight management programs than picking one at random.  This is likely a reason why one diet plan (low Carb/high Protein) is seen to work in one individual while not in another.¹³

The Diets.

Regardless of genotype, everybody benefits from eating an anti-inflammatory diet rich in antioxidants, healthy fats, fruits and vegetables, and whole grains.  Another key is approaching food as fuel and eating small meals and snacks about every three hours.  McDonald believes that determining the best “fuel” for your body depends on your genotype.

ApoE2 – For example, those with genotypes including ApoE2 prefer fat and operate optimally with 30 to 35 percent of daily calories from healthy fats such as olive oil, avocados, nuts, and omega 3-rich foods like salmon and walnuts.  A sample dinner for this genotype carrier might be salmon, broccoli with chopped almonds, and a baked potato.  A diet similar to the Adkins approach may be ideal for this phenotype.

ApoE3/3 - This genotype processes fat normally and does best with a moderate fat diet including slightly smaller portions of healthy fats, such as a dinner of salmon, green beans, and brown rice.  Exercise is likely a good aspect to focus on.

ApoE4 - People with genotype pairings containing ApoE4 don’t use fat for fuel very well and should aim for limiting it to 20 percent of total calories, deriving more calories from complex carbohydrates and plant proteins.  For example, dinner could be beans, rice, avocado, and broccoli.¹⁴

WellnessOne in Myrtle Beach and WellnessFirst in Charleston, SC have teamed up with a laboratory to test clients for ApoE variants, along with other in-depth cardiovascular and cancer biomarkers.  The center can also provide dietary protocol options and guidance.¹⁵

©2013

References:

1.       Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, et al. Gene dose of Apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. Aug 13 1993;261(5123):921-3.

2.       Corder EH, Saunders AM, Risch NJ, Strittmatter WJ, Schmechel DE, Gaskell PC Jr, et al. Protective effect of Apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat Genet. Jun 1994;7(2):180-4.

3.       Van Duijn CM, Clayton D, Chandra V, Fratiglioni L, Graves AB, Heyman A, et al. Familial aggregation of Alzheimer's disease and related disorders: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol. 1991;20 Suppl 2:S13-20.

4.       Huang W, Qiu C, von Strauss E, Winblad B, Fratiglioni L. APOE genotype, family history of dementia, and Alzheimer disease risk: a 6-year follow-up study. Arch Neurol. Dec 2004;61(12):1930-4.

5.       Small GW, Bookheimer SY, Thompson PM, Cole GM, Huang SC, Kepe V, et al. Current and future uses of neuroimaging for cognitively impaired patients. Lancet Neurol. Feb 2008;7(2):161-72.

6.       Keller L, Xu W, Wang HX, et al. The obesity related gene, FTO, interacts with APOE, and is associated with Alzheimer's disease risk: a prospective cohort study. J Alzheimers Dis. 2011;23(3):461-9.

7.       Huang Y, Zheng L, Halliday G, et al. Genetic polymorphisms in sigma-1 receptor and Apolipoprotein E interact to influence the severity of Alzheimer's disease. Curr Alzheimer Res. Nov 2011;8(7):765-70.

8.       Apolipoprotein E genotyping in Alzheimer's disease. National Institute on Aging/Alzheimer's Association Working Group. Lancet. Apr 20 1996;347(9008):1091-5.

9.       Author (1-9)  http://emedicine.medscape.com/article/1787482 (Alzheimer Disease and APOE4)

Gary W Small, MD  Professor of Psychiatry and Biobehavioral Sciences, Parlow-Solomon Professor on Aging, Director of Geriatric Psychiatry, Director of the UCLA Center on Aging, University of California, Los Angeles, David Geffen School of Medicine. 

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center. 

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference.

10.    http://www.hain-lifescience.de/en/products/human-genetics/ApoE/genotype-ApoE.html

11.    Corbo, R.M., Scacchi, R., Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a ‘thrifty’ allele?. Annals of Human Genetics, 1999; 63: 301–310.

12.    Corella, D., Tucker, K., et. al, Alcohol drinking determines the effect of the APOE locus on LDL-cholesterol concentrations in men: the Framingham Offspring Study, Am J Clin Nutr. 2001 73: 4 736-745.

13.    Berglund L. The APOE gene and diets--food (and drink) for thought. Am J Clin Nutr. 2001 Apr;73(4):669-70.

14.    WellnessOne/WellnessFirst, www.wellnessoneamerica.com and www.wellnessfirstcharleston.com

Fructose consumption can lead to low satiety and obesity

Lower satiety for fructose vs glucose drinks

An article by Ben Bouckley, Edited by Dr. Saleeby

Beverages high in fructose produce smaller increases in satiety hormones and associated feelings of satiety compared to drinks sweetened with the same amount of glucose, according to a new US study. The preliminary study, published in the January 2013 issue of the Journal of the American Medical Association (JAMA), assessed study participants using brain magnetic resonance imaging.

Introducing their research, Kathleen Page (Yale University School of Medicine) and colleagues said that increases in fructose consumption had shadowed rising obesity rates in the US, and that “high fructose diets are thought to promote weight gain and insulin resistance”.

The scientists found that drinking a 75g pure glucose preparation alone, and not a 75g pure fructose drink in isolation, reduced cerebral blood flow and activity in brain regions regulating appetite.

Ingestion of glucose alone produced increased ratings of satiety and fullness compared with fructose, which is very rarely used on its own as a beverage sweetener; high fructose corn syrup (HFCS) is processed to convert some of its glucose into fructose, to boost sweetness levels.

In an accompanying JAMA editorial, Jonathan Purnell and Damien Fair from Oregon Health & Science University said the study supported the “conceptual framework” linking fructose consumption to neurobiological pathway changes that promoted increased food intake.  “The major new finding reported by Page et al. is that the hypothalamic brain signal generated in response to fructose ingestion was statistically different from the response following glucose ingestion,” Purnell and Fair wrote.  “[A] difference was found and is accompanied by an increased sensation of fullness and satiety after glucose, but not fructose, consumption.”

Page et al. said that rat studies showed that ‘central administration’ (injection into hypothalamus) of fructose in rodents provoked feeding, Page et al. said, while glucose promoted satiety. “Thus, fructose possibly increases food-seeking behavior and increases food intake”.

But the current study authors admitted that no-one really understood the human implications of the relation between brain regions and glucose- or fructose- inspired animal feeding patterns.  Examining neurophysiological factors that could underlie associations between fructose consumption and weight gain, Page et al. recruited 20 healthy adults for two magnetic resonance imaging sessions.

The team found a significantly greater reduction in regional cerebral blood flow (CBF) in the hypothalamic region of the brain after glucose, rather than fructose, consumption.  “Glucose but not fructose ingestion reduced the activation of the hypothalamus, insula and striatum, brain regions that regulate appetite, motivation and reward processing,” Page et al. said.

“Glucose ingestion also increased functional connections between the hypothalamic-striatal network and increased satiety.”  The different responses to fructose were associated with reduced systemic levels of satiety-signaling hormone insulin, the scientists added.

Reference:

1.      Page,K.A., Chan,O., Arora.J, et al. 'Effects of Fructose vs Glucose on Regional Cerebral Blood Flow in Brain Regions Involved With Appetite and Reward Pathways'  Journal of the American Medical Association (JAMA), 2013;309(1):63-70.

2.      http://www.beveragedaily.com/content/view/print/712227

Medical Food Video Interview on The Balancing Act (TV)

Check out this vide on Medical Foods: 

 

http://www.tmedpharma.com/media/the-balancing-act-v1.php

12/14/12 The Future of Medical Foods - Nutraceuticals World

www.nutraceuticalsworld.com/contents/view_online-exclusives/2011-12-15/the-future-of-medical-foods/

The Future of Medical Foods
Metagenics conference stresses the importance of science as
the foundation of new therapeutic foods formulated to fight
against chronic illness and obesity.

By Joanna Cosgrove

Originally developed to use in the treatment of genetic metabolic diseases in infants, the evolution of medical
foods—products specially formulated to address specific health concerns—has gained steady momentum in
recent years, even earning formal recognition from FDA. The forerunner in the field, San Clemente, CA-based
Metagenics, Inc., delivered a series of workshop presentations on regulatory, research and business trends of
medical foods at the recent World Health Forum at Harvard Medical School. According to Metagenics’ Jeffrey
Bland, PhD, the company’s chief science officer and host of presentations, the future of food lies in the science
of nutrigenomics, the study of how food affects genetic expression at the cellular level.
“Medical foods taken with a low-glycemic Mediterranean diet have been tested and proven effective in reducing
metabolic syndrome, a condition that increases the likelihood of an individual developing heart disease, diabetes
and other lifestyle-related conditions,” noted Dr. Bland. “This discovery is a tremendous benefit to the healthcare
system. Now healthcare practitioners can expand their use of medical foods to help their patients to achieve
better health today, and for the rest of their lives.”
At Metagenics, Dr. Bland helms a team of more than 40 scientists in the field of nutrigenomics, where the
researchers test the phytonutrients found in plants for their health properties. Their work has earned more than
50 international and U.S. patents, and has been published in more than 80 peer-reviewed research journal
articles.
During his presentation, Willy Pardiñas, Metagenics’ senior vice president, general manager of Americas, spoke
about how scientific validation is the foundation for the acceptance and widespread use of promising medical
foods. “The companies that are succeeding with medical foods are those that demonstrate a commitment to real
science and evidence-based medicine,” he said. “They use the highest standards of clinical research including
the double-blind, placebo controlled studies. Now, traditional pharmaceutical companies are beginning to see the
value of medical foods as part of their portfolio, when these products bring clinical proof and broad applicability for
fighting chronic illness.”
J.D. Weir, president and CEO of Primus Pharmaceuticals, echoed Mr. Pardiñas’ sentiments on the principles of
solid science. “If we’re serious about giving healthcare practitioners real solutions for combating chronic disease,
they need to know our solutions work and can deliver predictable outcomes,” he said.
An estimated one-third of Americans currently have metabolic syndrome. Most of those afflicted with this
condition aren’t even aware they have it, or that it is putting them at greater risk of developing a chronic illness.
According to Metagenics, helping patients to reverse metabolic syndrome will significantly lower the number of
individuals who develop heart disease and diabetes, which in turn will fight the rapidly growing epidemic of these
ailments that is occurring around the world.
Robert Lerman, MD, PhD, medical director for Metagenics, moderated a session on the clinical application of
medical foods and cited research published earlier this year in the Journal of Clinical Lipidology on the effect of a
medical food in helping reverse metabolic syndrome. The article reported the findings of a 12-week multi-center
clinical trial conducted at three universities that showed Metagenics’ UltraMeal PLUS 360° medical food and a
low-glycemic Mediterranean diet is almost twice as likely to lower certain cardiovascular risk factors as this
same diet alone, and is 40% more likely to resolve the effects of metabolic syndrome.
Deanna Minich, PhD, Metagenics’ vice president of scientific affairs, addressed the importance of phytonutrients
in the medical food delivery form, while Matthew Tripp, PhD, vice president, research & development, spoke
about the breadth of active ingredients in medical foods that have an impact on chronic disease.
Next Generation Multi
In separate but related news, Metagenics recently announced the launch of a “professional brand” daily
supplement that was formulated in adherence to the same clinical standards as its aforementioned UltraMeal
PLUS 360° medical food.
According to the company, PhytoMulti is positioned as a “Smart Multi” daily supplement designed to “activate
health potential with a science-based combination of phytonutrients, vitamins, and minerals,” targeting “cellular
health to nourish cells, recharge cellular communication, and defend against free radical damage.
Metagenics said PhytoMulti was created using extensive research to develop a strategic combination of
phytonutrients—bioactive secondary metabolites in plant-based foods—known for their antioxidant properties and
“positive influence on cell signaling to communicate healthy messages throughout the body.” The proprietary
formulation of 13 concentrated plant extracts and phytonutrients (resveratrol, lutein, zeaxanthin and lycopene, as
well as an “optimized” blend of essential minerals and vitamins, including vitamin D3, folate and B12) was
scientifically tested for potential biological activity to protect cells via antioxidant capacity and maintenance of
DNA stability.
An independent laboratory evaluated PhytoMulti’s proprietary blend and the entire combination of
ingredients with the new total functional oxygen radical absorbance capacity (ORAC FN) assay that measures
against five major free radicals. Unlike a conventional ORAC, which tests against only one radical, this expanded
in vitro assay was said to have provided “a better sense of antioxidant protection against a variety of potentially
damaging free radicals and other reactive oxygen species.” The analysis of PhytoMulti’s active ingredients
(equivalent to the contents in one tablet) returned a total ORAC FN value of 12,600 trolox, demonstrating
“exceptional” antioxidant capacity.
Metagenics also said the potential of the phytonutrient blend to help maintain DNA stability was validated using
the COMET assay, a complex in vitro test using human immune cells. This assay demonstrated a 52% increase
in DNA stability when cells pretreated with the phytonutrient blend were compared to control cells introduced to
the same oxidative medium (peroxides).
PhytoMulti will be available January 1, 2012, through health practitioners nationwide. PhytoMulti with Iron,
formulated for those who need supplemental iron, will be available February 1, 2012.

Statins and Breast Cancer Risk

Studies put kibosh on statins for breast cancer prevention

By: BRUCE JANCIN, Family Practice News Digital Network

12/10/12

  | 

SAN ANTONIO – New data from the Women’s Health Initiative dash cold water on the idea that statin therapy reduces breast cancer risk.

The updated WHI findings showed no association between prior statin use and breast cancer risk in nearly 155,000 postmenopausal study participants followed prospectively for an average of 10.8 years.

Indeed, the annualized rate of breast cancer was 0.42% in 11,584 statin users and 0.42% in nonusers in this analysis of 7,430 first cases of invasive breast cancer, Dr. Pinkal Desai reported at the San Antonio Breast Cancer Symposium.

Statin potency, duration of use, lipophilicity versus hydrophilicity – none of those factors had any impact, added Dr. Desai of Providence Hospital Medical Center in Southfield, Mich.

In commenting on Dr. Desai’s WHI update at a session on statins and breast cancer risk, Dr. Vered Stearns noted that the new data represent quite a turnabout, since an earlier report from the WHI was one of the major initial triggers of interest in the notion that statins might protect against breast cancer.

That report (J. Natl. Cancer Inst. 2006;98:700-7) analyzed 4,383 cases of invasive breast cancer among study participants followed for a median of 6.7 years. It showed no reduction in breast cancer risk in association with statins overall; however, there was an 18% reduction in risk (P = .02) among users of lipophilic statins, including simvastatin, lovastatin, and fluvastatin. With longer follow-up and more cases, however, that earlier benefit is gone, observed Dr. Stearns of Johns Hopkins University, Baltimore.

Moreover, a new meta-analysis has put a further damper on the hypothesis that statins protect against breast cancer, she continued. The meta-analysis included 13 published cohort and 11 case-control studies with more than 2.4 million participants, including 76,759 breast cancer patients. The investigators, from the National Institute of Pharmaceutical Education and Research in Punjab, India, found that neither statin use overall nor long-term statin therapy affected breast cancer risk (Breast Cancer Res. Treat. 2012;135:261-9).

Dr. Desai noted that the latest WHI findings do contain one glimmer of hope regarding statins and breast cancer: In a multivariate analysis, women on simvastatin were 13% less likely to develop breast cancer than statin nonusers after adjustment for demographic factors, body mass index, smoking, alcohol intake, family history, age at menarche and at first birth, NSAID use, dietary fat, physical activity, and mammography within the past 2 years. However, this trend toward reduced breast cancer risk with simvastatin therapy didn’t achieve statistical significance.

Statins are safe and cheap, and multiple products are readily available. But in light of the discouraging new epidemiologic data, Dr. Stearns declared "I think that the effects of statins as single agents are modest at best. There’s quite a good rationale, though, for prospective studies of them in combination with standard hormonal therapy, chemotherapy, and radiation therapy, as well as with novel cancer treatment agents."

She added that the statins remain worthy of research interest because many of their pleomorphic cellular effects are antineoplastic. The drugs inhibit the mevalonate pathway, down-regulate metalloproteinases, inhibit Rho and Ras activation, decrease CD44 cells, and increase PTEN antibodies, all of which are salutary from an anticarcinogenesis standpoint.

Dr. Desai and Dr. Stearns reported having no financial conflicts of interest.

---

Copyright © 2012 International Medical News Group, LLC. All rights reserved. 
This page was printed from www.familypracticenews.com . For reprint inquires, call 877-652-5295, ext. 102.

American Fitness magazine (Nov/Dec 2012) issue





I write for American Fitness quite regularly and this latest issue my Lipotropic article was published.  Incidentially, Tony Horton (celebrity personal trainer) was the cover and featured article.  Very funny because back in 2009 I met Tony at a BeachBody coaches conference when I was asked to speak to the group in launching a meal replacement product called Shakeology.  I had just finished P90X and took Tony's aerobic class (aspects of P90X) and placed myself in the 2nd row.  The class was some 150 or 200 folks.  Was very cool to meet my ''hero'' of the P90X program that Sharon and I so diligently followed.

Any say hope you enjoy the article on Tony and my piece on Lipotropic agents:

Tony Horton Keeping on top by giving more By Cherryh Butler   It's true that most fitness professionals will never see the level of success that celebrity trainer Tony Horton has enjoyed, but the creator of the nation's top-selling workout series, P90X®, is confident that many can easily increase their business and profitability by doing a few specific things—walking the walk, being generous and having a passion for learning new skills. Horton, who set out decades ago to be an actor, but instead found his passion in the gym, believes the most successful trainers and instructors practice what they preach. They eat healthy, work out and take care of themselves. Horton says a trainer should be a role model to his clients. "If you are a trainer, lose the weight and walk the walk," he says. "Out of shape trainers that eat garbage won't be taken seriously. I can't show up at an event—even though I'm 54 years old—not cut and looking fit." YOU'VE GOT TO GIVE TO GET One of the best marketing tactics Horton has in his gym bag of tricks is giving freebies. "A lot of trainers who are fairly successful don't like doing this, but you have to," says Horton, who recently returned from a military base tour, where he volunteered his time. "I still do this to this day; obviously you can't do it all the time, but you can show up to a seminar, and if you are passionate about what you do, and your main focus isn't making money to buy some fancy car—if your passion is altruistic in nature, then you can build your business." DEVELOPING SKILLS No one knows everything about fitness, not even Horton, who recalls a recent track workout he did with four UCLA coaches. "You have to be as fit as you can possibly be, and that means you've got to work on your weaknesses and learn a lot about other techniques," he explains. "I know a little about speed and interval drills, but these guys kicked my ass. And they also gave me fresh ideas. To build your business you've got to be in shape, and you can't be afraid of fresh ideas." Getting stuck in just one type of fitness mode will kill any career. For example, Horton points out that there are only so many people who want to do yoga. The yoga instructor who adds something original to his class, like plyos or unique music, is going to build his business. "I'm not saying you need to throw kettlebells in your yoga class, but you have to find what it is that makes you special, and then find ways to advertise that. A lot of things are going to fail, but that shouldn't slow you down. You fall on your face and get up. People who succeed continue to ask questions of their mentors, but when the answers don't resonate, then you ignore them and keep moving forward." AF WHAT'S TONY DOING NOW? Tony Horton is on a mission to expand his fitness empire. Using the success of his fitness DVDs he's propelling his brand into other industries. For example, his latest project is Tony Horton Kitchen, a meal planning, delivery service to help people learn to eat healthier.  "A lot of people use exercise as an excuse to eat whatever they want, but exercise equals fitness and good food equals health," he says. "Without proper fuel—when one is fighting the other—you've got a problem." The main barriers to proper eating are that people don't have time to cook and that they are also addicted to chemicals found in most foods. Horton's way of eating solves those problems. The system delivers precooked meals to clients each week. They can choose the number of meals they get and also among menu options: vegetarian, vegan or flexitarian. Horton says, "You need a certain amount of variety when it comes to nutrition, and I've provided a meal plan that's tasty but filled with nutrients." Horton doesn't make any bones about the price; with meals costing about $11 each, it's not for a family of eight or a thrifty college student, but it is for someone who can afford to buy organic at a grocery store or eat out at restaurants. "We have organic vegetables, free-range buffalo and wild salmon," he says. "Yeah, wild salmon is expensive, so it's not for everybody, but it's not any more expensive than ordering those things at a restaurant. It shouldn't be a luxury that only rich people do." The next step will be a line of Tony Horton spices and sauces. But he isn't satisfied with staying in the kitchen—he's also working on a deal to endorse sunglasses designed for outdoor activities and is developing a sports clothing line with shoes being the ultimate end goal. A fitness watch may be in the future, too. Cherryh Butler is a certified personal trainer and group fitness instructor in Kansas City, Mo. She has a master's in journalism and contributes to magazines, newspapers and websites all over the country. YOGA, TONY HORTON STYLE "I can things at my age...not because I can do a bunch of pull-ups. It's because I do yoga." —Tony Horton Tony Horton is renowned as the creator and star of the P90X® extreme home fitness system, but many don't know about his yoga side. In the mid-1990s Horton discovered this form of exercise and it changed his life. "I had heard of yoga," says Horton. "But I thought it was silly." Then a woman he was dating invited him to a hatha yoga class. "I had my butt handed to me!" Horton understood that being bad at something was a good thing. And he began taking yoga classes regularly. He noticed that not only did yoga improve his flexibility and range of motion, it gave him more endurance during sports, such as rock climbing and skiing. "I found that yoga allowed me to push harder in all other aspects of fitness without getting hurt." Horton developed his first yoga video, the little known Ho' Ala ke Kino (Awaken the Body) in 1994. Later he worked with a variety of fitness experts developing and testing the 90-day program that was to become Power 90 Extreme, or P90X® for short. And in this system, he included the key element of his own fitness regimen—a full 90-minute yoga class: Yoga X. "A lot of people balked at the idea of an hour and a half yoga video," recalls Horton. "But every class I ever took was that long—so that's what I did." The practice is essential not only for one's physical well-being, but it can be used to deal with life stressors, such as being stuck in traffic or dealing with your boss. With yoga you are centered and connected. Horton endeavors to practice yoga at least twice per week. In addition, he explores various styles when traveling across the country. Horton says, "Every time I have a new teacher I feel like a beginner." Matthew Graham is an AFAA certified personal trainer and freelance writer.

November/December 2012

Introduction and Definition

A lipotropic agent is a compound that removes or inhibits the deposition of lipids (fats) in organs, specifically the liver. With recent weight management programs and the resurgence of the controversial hCG (human chorionic gonadotropin) protocol for weight loss, lipotropic agents like the MIC (Methionine, Inositol & Choline) injection and betaine are coming back into the limelight. To better understand the use of these agents as potential weight loss compounds, we must understand the physiology and pharmacology behind lipotropics.1

History

During the early 1930s, the properties of lipotropic agents were elucidated predominantly by the work of Charles H. Best, a researcher in the field of liver disease and lipid chemistry. There was intense interest in lipotropics with regard to treating particular liver disorders as one perceives with the many peer-reviewed medical journal citings during the 1930s and into the 1950s. The focus was on treatment of fatty liver disease, a problem where lipids accumulate in the hepatic cells. In 1954, Dr. Albert Simeons published his work on the use of a female hormone called hCG in a protocol for significant weight reductions in obese patients.2,3 Today this protocol is again gaining notoriety in a revised format, and with the aid of utilizing lipotropic agents.
Alcoholic fatty liver disease was noted to exist as early as the 1800s and agents were desired to help remove triglyceride or fat collections that poisoned the liver from overconsumption of alcoholic beverages. Nonalcoholic fatty liver disease, a fairly benign process at its onset, was eventually recognized to lead to a more worrisome disorder called NASH (Nonalcoholic Steatohepatitis) in the 1980s at the Mayo Clinic.4 Both nonalcoholic fatty liver and NASH are due primarily to obesity, dysglycemia (diabetes) and hypertriglyceridemia (elevated triglycerides).
A weight loss management program should not be of such narrow focus as to just drop unsightly fat from our bodies, but rather should include loss of visceral and organ fat as well. That is where lipotropic agents come into play. Not only may they be useful in mobilizing fats for weight loss, but they help in reversing the detrimental lipid build-up in organs, especially the liver, that can lead to disease and illness.

Research

The lipotropic agent betaine (trimethylglycine, TMG) is an example of an orally administered compound having dual functions as an osmolyte to protect cells, proteins and enzymes from environmental stress, as well as being a methyl group donor. Betaine is a natural extract from sugar beets and is derived from choline. An important function of betaine is to increase liver glutathione levels while lowering homocysteine concentrations. Betaine is able to synthesize l-methionine from the amino acid homocysteine. Biochemically it participates in the methionine cycle in the liver and kidneys as a methyl donor and neutralizer of free radicals and hydroxyl groups. Inadequate methyl group levels can lead to hypomethylation in important enzymatic pathways that affect hepatic proteins. This methyl group deficiency can result in elevated plasma homocysteine concentrations (known as an independent risk factor for coronary disease and stroke), and it can also result in inadequate fat metabolism leading to steatosis or fatty liver disease. With inadequate betaine consumption in our diet, the result is serum lipid abnormalities or dyslipidemia.5
Choline is a water-soluble essential nutrient and lipotropic agent often grouped with the B-family of vitamins. Choline protects the liver against environmental toxins and poisonings. One way choline protects the liver is by detoxifying amines, byproducts of protein metabolism. In one experiment liver cells were rescued with doses of choline in an intentional poisoning with carbon tetrachloride in laboratory animals.6 In our diet, the best source of choline is lecithin, also known as phosphatidylcholine.7 Lecithin is found naturally in egg yolk and soy beans. Choline goes through an oxidative process converting it to the metabolite betaine, itself a potent lipotropic and free radical scavenger. When we consume fat and lipids and they are absorbed in our alimentary tract, from there they are transported through the bloodstream to the liver in chylomicrons, a type of lipoprotein. Within the liver, these fats and cholesterol are packaged into very-low-density lipoproteins (VLDL) for transportation through blood to tissues that need them. Phosphatidylcholine, or choline, is a component of this transport VLDL particle and without it, the fat and cholesterol would accumulate in a negative way in the liver. Making sure there are no choline deficiencies in our diet, or even making available larger doses of choline, ensures us of mobilizing fat out of the liver and back into circulation to be used for fuel or other purposes by cells.
Dietary cholesterol was shown in experiments to slow down phospholipid turnover in the liver. Conversely, choline and betaine were shown by researchers Dr. Andrew J. Perlman and Dr. I.L. Chaikoff to speed up phospholipid metabolism within an hour after choline ingestion. The choline effects of mobilizing fats appear to linger for up to 12 hours after consumption.8 Diets high in refined grains (low in whole-grain breads, for example) have a relative deficiency in both betaine and choline. This is another reason why whole grains are preferred over refined or processed grains. Besides the lipid effects, low levels of dietary choline and betaine lead to elevated homocysteine levels and their untoward effects on the cardiovascular system.9
It’s noteworthy that the mitochondrial enzyme carnitine palmitoyltransferase-I (CPT-I) is responsible for fatty acid metabolism and is the rate-limiting step of the fatty acid oxidation pathway making it of interest in the treatment of obesity. Researchers feeding high-fat and choline-betaine deficient diets to laboratory animals noticed an increase in NASH with an inactivation or oxidation of the CPT-I mitochondrial enzyme activity.10 Modulation and manipulation of CPT-I may affect energy metabolism and food intake, and research is ongoing into the effects of both stimulation and inhibition of CPT-I and its relationship to obesity management.11
In 1937 Dr. Helen Tucker and Dr. H.C. Eckstein determined methionine to be a lipotropic agent. The experiments of Charles Best and Jessie Ridout showed that even small doses of methionine have the same effect on fat metabolism as higher doses.18,14 Methionine is an essential amino acid that helps the body take control of excessive serum levels of estrogen for one thing. High estrogen levels reduce bile concentrations that are responsible for fat emulsification and lipid passage through the liver. Methionine helps deactivate estrogens leading to improved fat metabolism and mobilization. It is well noted that elevated estrogen levels, especially in males, lead to unsightly adipose depositions and obesity. Overweight men have issues with feminization as their estrogen levels climb. Methionine, along with choline, detoxifies amines in protein metabolism. It also acts as a catalyst for choline and inositol functions. Methionine has another important function in that it affects the body’s levels of glutathione. Glutathione is a compound in the liver that is crucial in hepatic detoxification and acts as a very potent antioxidant. And glutathione is essential to defend the liver against toxic compounds that it metabolizes after oral ingestion.

Inositol (also known as myo-inositol) is a lipotropic agent whose action prevents the trapping of fat in the liver. Inositol is a compound classified as a carbohydrate, although not a classic sugar. It is found naturally in nuts, beans, melons and oranges. Once considered a member of the vitamin B-complex family, it was determined to be synthesized from glucose and thus lost the “vitamin” title as an essential nutrient. However, inositol does have a vital role in human health.15 Inositol and choline together prevent cholesterol from sticking to the arterial walls and inositol helps with the transport of fat through the blood stream.16 In a scientific study, it was demonstrated that choline exhibits more of a lipotropic effect than does inositol in laboratory animals fed both fat-free and fat-containing diets.28 Not to detract from the importance of inositol, it should also be noted that lipotropics tend to work in synergy with one another. Heavy consumption of caffeine can deplete inositol stores, and this may be one facet of how caffeinated beverage consumption today is leading to obesity and dysmetabolism. While each of these lipotropic agents acts alone as a fat-mobilizing compound, they are all related and interdependent upon each other in one fashion or another. Oftentimes the effects of lipotropics are symbiotic if not embellished by the others’ presence. It is very reasonable to coadminister two or more of these agents for best effect.

Use Today in Weight Loss and Health

Today as an adjunct to good nutritional counseling and appropriate dietary protocols for reductions in weight and adipose tissue, lipotropic agents can be used by doctors and nutritionists to help patients lose and control weight. Lipotropic agents certainly have their place among important nutraceutical considerations for weight management protocols. Both oral and intramuscular administration of lipotropics can aid in the maintenance and reduction of weight in those suffering from obesity, diabetes and metabolic syndrome.16 A very common lipotropic “cocktail” is the MIC, which is injected into deep muscle—usually on a weekly basis. Orally administered betaine can be taken as an alternative to the injected forms of the MIC preparation, having similar effects in most cases. There are few contraindications to the use of these lipotropic agents in moderation as they do occur naturally in healthy diets. However, super physiological doses should be administered under the careful supervision of a physician. AF


Yusuf Saleeby, MDis medical director of WellnessOne and WellnessFirst which offer extensive and advanced cardiovascular and stroke biomarker and genetic analysis, including lipid subtypes, Lp(a), HDL2 and HDL3, LDL1-4, ApoB, NT-proBNP, and the 4q25, 9p21, ApoE & KIF6 genotypes, and other evaluations. He is a regular contributor to American Fitness and is on the medical advisory board. He can be reached for comment at ymsaleeby@gmail.com.

REFERENCES: (use the link for full article:  http://americanfitness.squarespace.com/otp-1112/