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Natural Weight-loss Supplements:

by Mark Brudnak PhD ND(more info)

listed in weight loss, originally published in issue 75 - April 2002


As the population of the world expands, so too does its waistline. This is especially true for those people in Western, developed countries. Much of the increased obesity is probably due to the concomitant increase in processed food consumption per capita. While that issue is debatable, it does not detract from the point that there is an increasing awareness that obesity is a major problem. The need to control the problem has resulted in the mobilization of vast amounts of money by pharmaceutical companies to develop new drugs targeting various biochemical pathways involved in the production of fat. Anyone who has watched the evening news over the last year or two is aware that some of these new drugs can be fatal. Similarly, the natural products industry has tried to address the multibillion-dollar market by designing novel products, some of which have the potential to be equally dangerous. There are, however, natural alternatives and those will be discussed below. These natural products include such things as Hibiscus tea, L-arabinose, probiotics, d-limonene and perillyl alcohol, and phlorizin (phloridzin). These all-natural, essentially safe products are presented as an alternative to those that could be potentially lethal.

The Pharmaceutical and Natural Products Industries

Some sources have cited that as many as 60% of Americans are overweight. Weight is a major issue in American and Western health care. For this reason, drugs such as fenfluramine and dexfenfluramine (fen-phen), the latter of which has been shown to cause cardiac valvular dysfunction, have been developed, promoted and widely sold on the market to treat obesity. Fortunately, fen-phen has been withdrawn, but not before serious damage was done to many people.

Other pharmaceuticals include compounds that block the absorption of fat, such as Orlistat. This compound prevents up to one-third of the fat in the food you eat from being digested. This undigested fat in the food you eat is then eliminated in your bowel movements. Side effects that may occur while taking this medicine include oily stools or spotting, increased number of bowel movements, bowel movement urgency, poor bowel movement control, or gas with discharge. Such side effects can result in a range of problems from the annoying to devastatingly embarrassing. At the very least, it could make travel difficult.

The natural products industry has come up with some of its own ideas, which are touted as natural alternatives to the above products. However, some of these also have potentially disastrous side effects. Recently, products have shown up in the US market that claim to block sugar absorption. These products contain relatively large amounts (upwards of 700mg) of kidney bean (Phaseolus vulgaricus) extract. Legumes in general are known to contain large amounts of lectins. Lectins are a class of non-immune non-enzymatic glycoproteins that specifically bind sugars. In this case the lectin is called PHA. PHA is a tetramer existing either as a homo- or heterotetramer consisting of two different subunits and is given the designations '-L' or '-E' depending on the ratio of the subunits.

In addition to the ability to bind sugars, at low levels, lectins are also used as potent mitogens in the lab. Additionally, lectins are also efficient mutagens at higher levels. At even higher levels, lectins become cytotoxic. We have shown a typical killing curve employing PHA-L against mouse thymocytes (see below).[1] Cell death results at very low concentrations of the lectin. In fact, the concentrations of the lectin are much lower than those that might be obtained from the ingestion of the purported sugar absorption blockers. At the very least, the sugar blockers could often achieve mitogenic or mutagenic concentrations.

Our laboratory has shown that ovary cells grown in the presence of a cytotoxic lectin, PHA, can be easily and quantifiably killed. Visible cell death results from as low as 40ug/ml of lectin. At twice that concentration, 80ug/ml, cell survival drops to close to zero. All other colonel isolates tested showed similar results, as did cells from other tissues including fibroblasts (skin cells) and thymocytes (T-cells).[1]

While it is certainly true that kidney beans contain amylase inhibitors, it is equally true that they can be potentially deadly. The reason is that beans contain compounds that are mitogenic (cause cells to divide rapidly - a step in the progression of cancer), mutagenic (they mutate the cells - another step in cancer) and cytotoxic (they kill cells!). People may be taking many times the amount needed for those effects. They will not notice anything for probably a few years, but it is conceivable that there will be a whole lot of people with gastrointestinal cancer!

Usually, beans are perfectly safe, but uncooked beans, and this has been known for years, are extremely dangerous. If one feeds uncooked (cooking destroys the toxic proteins known as lectins) beans to animals, due to the mitogenic effect, the size of an internal organ can actually double! This is insane. While it is terrible that people are going to be hurt, it demonstrates, quite poignantly, the need for technical people who understand the biology of what they are formulating.

Where does that leave one? Are there any alternatives? Fortunately the answer is a resounding 'yes'.

The Natural, Safe Alternatives

Hibiscus Tea

Based on a similar idea to the amylase inhibitors in kidney beans, Hibiscus tea has been shown to contain porcine pancreatic amylase inhibitors. Hansawasdi et al.[2] recently reported ?-amylase inhibitors in Rosell (Hibiscus sabdariffa Linn.) tea. Hibiscus acid was shown to be the major constituent responsible for the inhibition. While a methanol extract of the tea was used, because hibiscus acid is a major constituent of the tea it should be very possible to use a fine powder of just the tea in a formulation. This makes a great deal of sense for the natural products industry, as whole green tea has similarly been shown to have potential in the area of weight loss (lipid metabolism).[3] While it is not known exactly how it works, it is known that it is a non-competitive inhibitor. Also, it is entirely possible that it could be functioning as a genomeceutical (natural compound capable of affecting gene functionality), by altering the expression of the enzymes.[1]


One such alternative is L-arabinose. L-arabinose has been reported by Osaki et al. to inhibit sucrase.[4] They studied the effects of the poorly metabolized sugar L-arabinose in rats for its ability to inhibit the sucrase enzyme. By inhibiting this enzyme, the sucrose is not converted to fructose and glucose, which would ordinarily be used to build fat. Arabinose is a very common sugar and should be completely safe. In fact, it has been sold for years as a food grade material and is commonly used as a pharmaceutical precursor for the manufacture of drugs. However, it is a natural product and available as a supplement.


Additionally, probiotics can be employed to assist in the digestion of excess L-arabinose. Probiotics can be defines as: viable single or mixed culture micro-organisms, which when applied to animal or man, beneficially affect their host by improving the properties of the indigenous microflora.[5] It has been shown that lactic acid bacteria can metabolize L-arabinose. Specifically, Lactobacillus plantarum has this property.[6] Given the similarities of the probiotic strains, there is every reason to suspect that other strains such as Lactobacillus acidophilus and Bifidobacterium lactis (bifidum) should similarly be able to ferment any lingering arabinose to prevent gastrointestinal discomfort due to flatulence. High-quality strains with proven stability and produced by reputable manufacturers should be selected.

Monoterpenes D-Limonene and Perillyl Alcohol

The monoterpenes, such as d-limonene (DL) and perillyl alcohol (POH), are yet another safe alternative. They have been used for years in the area of cancer prevention and therapy with excellent results.[7] DL is a monocyclic MT with POH a metabolite of d-limonene, being its hydroxylated form. There are a number of synonyms for limonene, including the following: 1,8(9)-p-Menthadiene; 1-methyl-4-(1-methylethenyl)clyclohexene; 1-methyl-4-isopropenyl-1-cyclo-hexene; alpha-limonene; dipentene; limonene; p-mentha-1,8-diene. The monoterpenes are quite innocuous and are found in essential oils of many plants including lemons, oranges, grapefruit, caraway, dill, bergamot, peppermint, spearmint, grasses and tomatoes. They are also associated with vegetables and some evergreen trees.[8] POH is often distilled from lavender, found in cherries, mint, celery seeds[9] and can be produced synthetically. It is typically used as a flavouring agent, food additive and fragrance, and has been found to be a major volatile component of mother's milk.[8]

D-limonene has different metabolites for different animals. In humans, the three major metabolites after an oral dosage are perillic acid, dihydroperillic acid and limonene-1,2-diol. It is thought that the metabolic precursors of the first two are perillyl alcohol and perillyl aldehyde.[9] Moreover, many people regularly consume DL every day without even knowing it. This is because DL is found in things such as orange juice at concentrations ranging from 10-100ppm and chewing gum which contains up to 2,300ppm.[8]

The bulk of the toxicity data for the monoterpenes comes from the study of limonene in animals and has been well presented by Von Burg.8 Monoterpenes are cited in the literature as being anorexics.[10] They naturally decrease the appetite! As natural appetite suppressants, their potential application to weight loss and diet aids is enormous. To summarize briefly the toxicology data, limonene can cause skin sensitization in susceptible people. A blood clearance rate of 1.1 l /kg/hr has been established, with the majority being eliminated through the urine. There appears to be no genotoxicity (Ames test), though straight orange peel oil was found to have slight promotional activity for mouse skin tumours initiated with (DMBA).

However, the promotional activity was not observed when either limonene or straight orange peel oil were added to the diet, suggesting a relationship between promotion and irritant properties of the straight oil. Similarly, there appears to be no neurotoxicity. It should be noted that when relatively high dosages (2,363mg kg-1) were orally administered to mice, decreased body weight and increased bone abnormalities were observed in foetuses. However, at lower dosages (591mg kg-1), no effects were seen, either maternally or in the foetus. Theoretically, there is a possible lethal oral dose for humans in the range of 0.5-5g/kg. However, that translates to 35-350 grams for the average 70kg male, and they have been shown to be well tolerated in rats at as high as 2.5% of the diet.


Phlorizin (Phloridzin) is another exciting compound. Brichard et al. have shown its potential for diabetics, but the cross-over to weight-loss products is apparent.[11] They demonstrated that phlorizin, which can be extracted from apples, may induce a partial shift of the predominating gluconeogenesis. This can be associated with liver glucose overproduction, into glycolysis, by normalizing the faulty pretranslational machinery. They theorize that this could occur by resorting alpha cell function and thereby lowering hyperglucagonaemia. Obviously, based on its effect on mRNA levels, phlorizin is a genomeceutical.11 Recently, other work has confirmed this.[12]


It should now be apparent that there are several comparatively safe and efficacious natural products, which can be used as alternatives to pharmaceutical compounds. These include not just substances that act on biochemical pathways, but also those that act on genomic multi-level nutrient-sensing pathways. Such genomeceuticals are going to have far-reaching effects as the natural products industry matures into a responsible, science-based health-care system. Recently, a gene has been reported,[13] ACC2, without which mice eating much more than other controls still weighed 10-15% less! It is only a matter of time until genomeceuticals are found which can naturally down-regulate the expression of ACC2. The possibilities are virtually endless and we are only at the beginning of this burgeoning area of nutrients directed towards the genome.[14]


1. Brudnak MA. Application of genomeceuticals to the molecular and immunological aspects of autism. Medical Hypotheses. In Press.
2. Hansawasdi C, Kawabata J and Kasai T. Alpha-amylase inhibitors from roselle (Hibiscus sabdariffa linn.). Biosci Biotechnol Biochem. 64(5): 1041-3. May 2000.
3. Sayama K, Lin S, Zheng G and Oguni I. In vivo effects of green tea on growth, food utilization and lipid metabolism in mice. 14(4): 481-4. Jul-Aug 2000.
4. Osaki S, Kimura T, Sugimoto T, Hizukuri S and Iritani N. L-arabinose feeding prevents increases due to dietary sucrose in lipogenic enzymes and triacylglycerol levels in rats. J Nutr. 131(3): 796-9. Mar 2001.
5. Huis in't Veld JH, Havenaar R and Marteau P. Establishing a scientific basis for probiotic R&D. Trends Biotechnol. 12(1): 6-8. Jan 1994.
6. Gobbetti M, Lavermicocca P, Minervini F, de Angelis M and Corsetti A. Arabinose fermentation by Lactobacillus plantarum in sourdough with added pentosans and alphaalpha-L-arabinofuranosidase: a tool to increase the production of acetic acid. J Appl Microbiol. 88(2): 317-24. Feb 2000.
7. Brudnak MA. Cancer preventing properties of essential oil monoterpenes d-limonene and perillyl alcohol. Poss. Health. 53: 23-25. 2000.
8. Von Burg R. Limonene. Journal of Applied Toxicology. 15(6): 495-9. Nov-Dec 1995.
9. Hohl RJ. Monoterpenes as regulators of malignant cell proliferation. Advances in Experimental Medicine and Biology. 401: 137-46. 1996.
10. Ripple GH, Gould MN, Arzoomanian RZ, Alberti D, Feierabend C, Simon K, Binger K, Tutsch KD, Pomplun M, Wahamaki A, Marnocha R, Wilding G and Bailey HH. Phase I clinical and pharmacokinetic study of perillyl alcohol administered four times a day. Clin Cancer Res. 6(2): 390-6. Feb 2000.
11. Brichard SM, Henquin JC and Girard J. Phlorizin treatment of diabetic rats partially reverses the abnormal expression of genes involved in hepatic glucose metabolism. Diabetologia. 36: 292-98. 1993.
12. Goda T. Regulation of the expression of carbohydrate digestion/absorption-related genes. Br J Nutr. 84(Suppl 2): S245-8. Dec 2000.
13. Wakil et al. Science. 30 March 2001.
14. Brudnak MA. Nutrients directed toward the genome. Townsend Letter for Doctors & Patients. 207: 74-76. October 2000.


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About Mark Brudnak PhD ND

Mark A Brudnak PhD ND has authored over 40 peer-reviewed scientific and trade journal articles and is recognized worldwide as a leading expert in the areas of probiotics and enzyme. Brudnak has written or contributed to books such as The Probiotic Solution, Probiotics For Dummies, PCR In Neuroscience, Pathway Cloning: Investigation Of A Novel Eurkaryotic Cloning And Cellular Engineering System. Dr Brudnak was the Technical Director for MAK Wood, Inc., where his duties include technical writing, research, and product support/development. His major areas of interest are anti-cancer nutrients, enzyme therapy, pro/prebiotics and biologically active carbohydrates and peptides. Dr Brudnak is also a board-certified naturopath, maintaining a natural health consulting practice in Grafton, WI USA and can be reached via

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