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 They are now popularly used in many weight loss management programs.
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.
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