(for references cited see Bibliography)

Bitter Orange (Citrus aurantium; Zhi shi).

Bitter Orange is the Chinese herb Zhi shi (immature Bitter Orange; Citrus aurantium), used both as the herb itself and as an extract. It contains alkaloids which are mild sympathicomimetics (also called adrenergic agents) and have useful effects on metabolism and breakdown of fat, that is, they increase the metabolic rate, and they also increase the rate of breakdown of stored fat (lipolysis) in the body (Jones, 1998). The alkaloids present in Bitter Orange include synephrine, hordenine, octopamine, tyramine and N-methyltyramine:

While foods and medicinal herbs derived from Citrus species have been used, and continue to be used, for a variety of food purposes and for their health benefits, they have not previously been identified as herbs or plants which have value in the treatment of weight problems or for improving physical performance and fitness (Jones, 2001, 2002). In part, this is due to the fact that levels of the active agents in most Citrus products are low; highest levels are found in parts of the plants that are not normally eaten, or in immature plants. For example, levels of these agents in orange juice are expressed in parts per million, or even parts per billion. In practical terms, that means drinking 40 or more pints of orange juice per day, or eating 80 oranges, to get the intake of the active agents that would be obtained from one or two capsules, tablets or bars containing Bitter Orange extract.

The main adrenergic amines (alkaloids) of Bitter Orange (Citrus aurantium) extract are synephrine and N-methyltyramine, which act almost wholly indirectly and are active by mouth. Synephrine is used medicinally in Europe, but has been replaced in North America by ephedrine and pseudo-ephedrine.

In classical tests, these citrus alkaloids show properties similar to ephedrine (Goodmore and Gilman, 1941), with activation of of β-receptors (Munson, 1995). More recently, studies have shown that both octopamine and synephrine appear particularly effective in stimulating lipolysis (Carpene et al., 1999; Fontana et al., 2000), a postulated β3-receptor effect (Dulloo, 1993). Wenke et al. (1967) had previously revealed that synephrine was about 3.5 times as effective in stimulating lipolysis as octopamine. There are thus indications that the alkaloid mixture in Bitter Orange is superior to the mixture of ephedrine alkaloids in Ma-huang (Ephedra sinica) in terms of effects on β-receptors in general. However, this theoretical superiority does not extend to the field of side effects. Initial studies in lean volunteers (Hedrei & Gougeon, 1997) and obese volunteers (Pathak & Gougeon, 1998), while showing excellent thermogenic responses, failed to reveal any evidence of increased heart rate, blood pressure or central nervous system stimulation.

Further reported studies in volunteers have confirmed the thermogenic actions and the absence of side effects (Gougeon et al., 2001, 2003, 2005), while a clinical study reported by Colker et al. (1999) also demonstrated a thermogenic effect and excellent effects on weight loss, but with an even more dramatic effect on fat loss, again with a total absence of side effects.

Thus though the Citrus alkaloids appear to be at least as thermogenic as the ephedrine alkaloids, they are clearly gentler than the latter and do not cause the minor side effects associated with use of Ma huang (nervousness, agitation, palpitations, increases in blood pressure). The better tolerance of the Citrus alkaloids is thought to be because they do not pass so readily into the brain, and may target fat cells rather more specifically.

The actions of the Citrus alkaloids can therefore best be described as those characteristic of mild indirect-acting sympathicomimetic agents (also known as adrenergic agents), which usually elicit release of noradrenaline (norepinephrine) from presynaptic sites. This in turn activates both α- and β-adrenoceptors. In the case of the Citrus alkaloids alkaloids, however, there is evidence that dopamine is also released from the presynaptic sites (Hedrei & Gougeon, 1997); dopamine is present in these sites, but generally serves only as a precursor for noradrenaline. As far as noradrenaline is concerned, the perceived effects on different organs and tissues depend on the relative proportions of the two types of receptors, which mediate different responses. At a basal level, classical pharmacology teaches that α-activation results in contraction of smooth muscle (except for intestinal smooth muscle) while β-activation causes relaxation of smooth muscle and stimulation of the myocardium. But this picture is complicated by the fact that both α- and β-receptors can be subdivided into further types with differing distributions and sensitivities, and may be even further complicated by the possibility that sensitivities to dopamine may not parallel those for noradrenaline.

At a cellular level, activation of β-receptors results in stimulation of adenylate cyclase. This leads to increases in intracellular levels of cyclic adenosine monophosphate (cAMP), which, through a complicated mechanism, results in the observed reactions. The β-receptors can also be further subdivided into β1, β2, and β3 types, the last of which is strongly believed to be responsible for the lipolytic and thermogenic effects of adrenergic agents, while interactions with the other two types of β-receptors are known to control cardiac effects.

Effects on blood pressure, however, are in part due to the activation of α-receptors.

Central nervous system effects of adrenergic agents appear to depend on activation both α- and β-receptors (with the exception of β3-receptors). The multi-receptor response is also important in explaining observed synergistic effects of caffeine on certain actions of adrenergic agents. The overall response to such agents, reflected in perceived effects, is governed by the distribution of receptors in terms of types and populations. As an example, the activation of β-receptors causes vasodilation of vessels in the heart and skeletal muscle while simultaneous α-activation results in vasoconstriction in other vascular beds. This is effectively the classical "fight or flight" response, which together with other metabolic results of adrenoceptor activation is intended to put the body into an optimal state for physical exertion.

The metabolic results of adrenoceptor activation also include effects on lipolysis and thermogenesis. In the case of lipolysis, activation of certain α-receptors inhibits the process, while activation of β3-receptors stimulates lipolysis and at same time, possibly in part due to increased availability of substrate, induces a thermogenic response. The overall response of the adipose tissue thus depends on the relative proportions of α- and β3-receptors. A high ratio would produce a comparatively lower thermogenic response than a low ratio.

The diminishment of thermogenic response associated with the increasing proportion of α-receptors may explain why some studies of thermogenic responses to adrenergic activation identify two populations: responders and relative non-responders.

Though the above represents the generally accepted explanation of the actions of adrenergic agents, initial clinical observations with the Citrus alkaloids have failed to reveal cardiovascular effects (increased pulse rate and blood pressure) or undue stimulation of the central nervous system, which would be typical of, for example, the ephedrine alkaloids from Ephedra sinica (Ma-huang). These observations do, however, show an obvious effect on thermogenesis (Hedrei and Gougeon, 1997; Pathak and Gougeon, 1998), with a concomitant effect on weight loss and a substantial stimulation of fat loss (Colker et al., 1999). The lack of central nervous system effects can be attributed to the relatively low lipophilicity of the Citrus alkaloids, which will slow their passage across the blood-brain barrier. However, the absence of cardiovascular activity implies that the Citrus alkaloids have little effect on α-, β1- and β2-receptors, while the thermogenic effect confirms that they do activate the peripheral β3-receptors.

Part of the explanation for this unusual dissociation may be found in the fact that Citrus alkaloids alkaloids appear to release dopamine and noradrenaline from the presynaptic sites, and that while there are satisfactory mechanisms for the re-uptake of noradrenaline, the dopamine released could remain longer in the synaptic gap, prolonging the activation of β3-receptors. It could be speculated that though dopamine is similar to noradrenaline in properties, it may differ in specificity and preference for β3-receptors. However, recent studies have shown that both octopamine and synephrine, alkaloids in the extract, are β3-receptor agonists in mammalian cells (Carpene et al., 1999; Fontana et al., 2000). Wenke et al. (1967) had previously demonstrated that octopamine had a significant lipolytic effect, but that synephrine was about 3.5 times as potent, also indicating that these components of the Citrus alkaloids have high specificity for β3-receptors.

Thus while there is some direct evidence from actual receptor studies that two of the Citrus alkaloids (octopamine and synephrine) show specificity for β3-receptors, the experimental evidence from studies in humans suggests strongly that this must indeed be one of the main mechanisms of action:

  • In volunteers, no evidence of cardiovascular effects after single or repeated doses, but significant increases in metabolic rate.
  • In obese subjects, significant increases in rates of weight loss, due almost entirely to fat loss (a consequence of lipolysis), but no evidence of any side effects or changes in cardiovascular parameters.

These observations indicate relative absence of effects on α-, β1- and β2-receptors, but a strong effect on β3-receptors. It remains to be determined whether this is due to peripheral dopamine effects, is a possible consequence of disassociation of the actions of alkaloids in the mixture, or is a result of both the postulated mechanisms.

Increasing the metabolic rate is beneficial in weight loss, since the metabolism becomes sluggish in overweight and obese subjects placed on low calorie diets; by increasing the metabolic rate, weight loss is improved. Since the breakdown of stored fat is also increased, more of the weight lost comes from fat, and body protein from lean tissues is spared, thus helping prevent the loss of lean body mass that also often occurs during dieting.

While the actions of adrenergic agents that demonstrate good thermogenesis without significant cardiovascular and central nervous system effects make them ideal adjuncts for regulating and controlling weight problems, they can also be useful as ergogenic aids to improve physical performance (Yang and McElligott, 1989). The acute action is to increase energy availability and, thus, increase the capacity for physical exertion, while longer-term actions result in an increase in muscle mass, particularly when combined with appropriate diet programs and training. Indeed, it has been suggested that such agents may act as very effective anabolic agents when given over long periods of time. Both the beneficial ergogenic effects and the valuable effects on weight loss stem from the combination of the effects on lipolysis and the thermogenic effects. Thus by increasing the rate at which fat is released from body stores (lipolysis), while simultaneously increasing the metabolic rate (thermogenesis), the removal of unwanted fat stores is accelerated.

Since there is increased availability of substrates (the free fatty acids which are released from the fat stores) for oxidation, the body has access to greater amounts of energy. The body's use of these substrates spares protein that might otherwise be oxidized for energy. Used conjointly with a high protein intake and an exercise program, this can result in increased availability of amino acids for incorporation into protein in the muscle mass.

It should be noted that an adequate essential fatty acid status, both in terms of intake and balance, is necessary for optimal thermogenesis.

Nutmeg (Myristica fragrans).

Nutmegs are the dried seeds of Myristica fragrans, an evergreen tree indigenous to the Molucca Islands but now widely cultivated throughout Indonesia and in parts of India, Sri Lanka and the West Indies. They contain 5% - 15% of a volatile oil, which in turn contains about 4% myristicin and 2% elemicin and isoelemicin. Myristicin and elemicin are lipophilic and cross the blood-brain barrier readily.

Myristicin is 4-allyl-6-methoxy-1,2-methylenedioxybenzene, while elemicin is 1-allyl-3,4,5-trimethoxybenzene. Both possess a carbon skeleton that is conformationally identical to the amphetamines:

The transformation of myristicin and elemicin to the corresponding amphetamines can readily be achieved by chemical means, but it has been indicated that these transformations can also be effected biologically. Hydroxylation of the allyl group is a known biological process, and subsequent transamination (also a known process) would immediately yield an amphetamine. Both myristicin and intact nutmeg have been shown to possess central nervous system activity (Truitt et al., 1961), and myristicin has been shown to increase brain serotonin levels (Truitt et al., 1963), which would result in an increase in satiety. It has been variously suggested that myristicin and elemicin may also be converted by transamination in the brain into amphetamine-like substances with hunger-suppressant effects (Shulgin, 1966), or that myristicin, which has a weak mono-amine oxidase inhibiting effect, could compete with noradrenaline as a substrate for mono-amine oxidase, thus increasing noradrenaline levels with consequent hunger-suppressant actions (Truitt, 1967). It is probable that these enzymatically-mediated changes do indeed occur in the human body to some extent, since this would explain the similarity of the physiological activities of myristicin to those of the amphetamines. In view of the lack of peripheral activity of myristicin, it is also probable that the substance passes the blood-brain barrier and undergoes further transformation in the central nervous system. Since the molecule is lipophilic, it would cross the blood-brain barrier readily, and may exert an anorexic effect, of value in inducing weight loss, by inhibition of the hunger centre.

Guarana (Paullinia cupana):

Guarana is the dried paste made from the crushed seeds of P. cupana or P. sorbilis. The plant is a fast-growing woody perennial shrub native to Brazil and other regions of the Amazon. It bears orange-yellow fruits that contain up to three seeds each. The seeds are collected and dry roasted over fires. For use as the native herb, the kernels are ground to a paste with cassava and molded into cylindrical sticks, which are then sun dried.

Mildly aromatic odour, the taste is astringent and bitter with vague chocolate-like notes. The native herb contains up to 5% caffeine and related methylxanthines, depending on variables such as agronomic, geographical and climatic factors:

Guarana is well known as a caffeinaceous herb. The methylxanthine in guarana is predominantly caffeine, which is a mild central nervous system stimulant, but also has other beneficial physiological actions. Mechanisms of action of caffeine and other methylxanthines are not well understood, but their main effects are due to the inhibition of phosphodiesterase, causing accumulation of cAMP, and they may also block adenosine receptors. The methylxanthines act as respiratory and CNS stimulants, smooth muscle relaxants, diuretics, cardiac stimulants and stimulants of skeletal muscle.

At an empirical level, caffeine has long been known as a thermogenic substance that is capable of increasing the resting metabolic rate (RMR) and increasing lipolysis, that is, the increase in breakdown of triglycerides (fat) in adipose tissue stores, and these actions are referenced in many standard reference works. The actions of interest in this respect appear to be consequent on the inhibition of phosphodiesterase, causing accumulation of cAMP, and the blockade of adenosine receptors (Munson, 1995), but Astrup et al. (1990b) notes that the exact mechanisms by which caffeine increases thermogenesis (which is effectively an increase in RMR and is generally measured by resting energy expenditure, EE) remain obscure.

There is general scientific consensus only over the facts that caffeine is indeed a thermogenic substance which increases RMR and lipolysis, and thus has potential for use in weight loss regimes, and much discussion over how this is actually mediated at cellular or intracellular level.

Practically, Astrup et al. (opus cit.) showed that ingestion of 100 mg caffeine by volunteers resulted in a significant increase in EE (p < 0.05 vs. placebo), and that this increase was due to increased oxidation of both carbohydrate and fat. In this study, caffeine had a pronounced impact on plasma glycerol and non-esterified fatty acids, both of which rose considerably, but little effect on glucose, indicating that lipolysis was increased substantially. Since lactate levels also increased, the authors speculate that the caffeine may have triggered the Cori cycle, which is a thermogenic cycle in muscle and adipose tissue that results in lactate as an end product. Astrup et al. (1992d) also note that, in humans, caffeine stimulates thermogenesis and lipolysis dose-dependently, and that the thermogenic effect may be related to both a skeletal muscle component and the extracellular fatty acid/triglyceride cycle. Broadly similar findings have been reported in rodents by, inter alia, Bukowiecki et al. (1983) and Cheung et al. (1988); in rodents caffeine promotes weight loss by reducing lipid stores through increased EE but without decreasing energy intake.

In relation to weight loss, Yoshida et al. (1994) showed that the body weight loss in obese women showed a significant correlation with their thermogenic response to caffeine, in other words that those who have the best response to caffeine also have the best rates of weight loss. Other recent studies of note are by Collins et al. (1994), which shows significant increases in RMR lasting several hours after ingestion of caffeine or smoking, with an additive effect of the two, and Tagliabue et al. (1994), who state "The ingestion of coffee is an everyday condition that increases the metabolic rate. The thermic effect of caffeine has been known since 1915 and has been extensively investigated in many recent papers".

Ginkgo (Ginkgo biloba).

Also known as maidenhair tree or kew tree, the ginkgo is the world's oldest living tree species, and it can be traced back more than 200 million years to the fossils of the Permian period. It is the sole survivor of the family Ginkgoaceae. Individual trees may live as long as 1000 years. They grow to a height of a about 125 feet and bear fan-shaped leaves. The species is dioecious; male trees more than 20 years old blossom in the spring. Adult female trees produce a plum-like gray-tan fruit that falls in late autumn. Its fleshy pulp has a foul, offensive odor and causes contact dermatitis. The edible inner seed resembles an almond and is sold in oriental markets. The gingko species was almost destroyed during the ice age but survived in China, where it was cultivated as a sacred tree and is still found decorating Buddhist temples throughout Asia. Preparations have been used as health remedies for more than a thousand years. Traditional Chinese physicians used ginkgo leaves to treat asthma and chillblains, which is the swelling of the hands and feet from exposure to damp cold. The ancient Chinese and Japanese ate roasted ginkgo seeds, and considered them a digestive aid and preventive for drunkenness.

The leaves are 1" - 2" long, oddly fan-shaped, slightly thickened, slightly wavy on broad edge, often 2-lobed with fine forking parallel veins but no midvein. A dull-light green turning yellow in autumn. The herb is usually the leaves, which are most active when picked in the Fall, though both the seeds and the leaves are used in Traditional Chinese Medicine. The leaves contain a number of active substances, and extensive research has shown that these substances can dilate blood vessels and improve the circulation. They can also prevent aggregation of blood platelets, which is one of the first stages in thrombosis. Practically, the improvement of the circulation resulting from ginkgo treatment, particularly in older subjects, can manifest as improvement in memory and brain function, improvement in vision (particularly in diabetic patients), or reduction in cramps in those suffering from poor circulation in the limbs. Ginkgo also appears to have antioxidant properties, and it has been suggested that use of natural biological antioxidants may slow the aging process.

The leaves contain a number of active substances, mainly flavone glycosides (including quercetin and kaempferol) and terpene lactones (the ginkgolides):

The contents of active substances show seasonal variation, with highest levels in the autumn. Standardized extracts are often used instead of the powdered leaves.

Historically, Ginkgo is one of the oldest Chinese Traditional Medicines, and is apparently mentioned in the Ben Cao Chien as well as in other monumental works from the 15th and 16th Centuries (Lan Mao's Dian Nan Ben Cao and Liu Wen-Tai's Ben Cao Pin Hui Jing Yao).

In animals, ginkgo extracts have been shown to improve memory and learning ability in mice (Chen et al., 1991; Winter, 1991), increase the rate of inner ear recovery after experimental inner ear trauma in cats (Lacour et al., 1991), inhibit or decrease allergic manifestations in mice and rats (Zhang et al., 1990), improve nutrient utilization in pig aorta cells (Bruel et al., 1989), facilitate recovery from brain damage in rats (Attella et al., 1989) and protect against ischaemic brain damage in rats (Krieglstein et al., 1986).

In humans, Grassel (1992) showed that ginkgo extracts inproved mental performance in patients with cerebral insufficiency, while Raabe et al. (1991) showed that vision improved in elderly patients with cerebroretinal ischaemia after treatment with ginkgo extracts. In another study, elderly patients with mild to moderate memory impairment showed significant improvement in cognitive function after ginkgo treatment (Rai et al., 1991). Eckmann (1990) showed that symptoms associated with cerebral insufficiency (mainly depression) generally improved after treatment with ginkgo extract for 2 - 4 weeks, while Fünfgeld (1989) reported improved electroencephalographic patterns and clinical findings in patients with Parkinson's disease. Hofferberth (1989) reported significant improvements after ginkgo treatment in patients with psychotic syndromes associated with organic brain changes.

Colour vision defects in patients with diabetic retinopathy also diminished under ginkgo treatment (Lanthony and Cosson, 1988), while ginkgo extracts improved microcirculation in capillaries in both volunteers (Jung et al., 1990) and in patients with arteriosclerotic changes of extracranial brain arteries (Koltringer et al., 1989).

Huang (1993) also notes that Ginkgo may reduce blood pressure (a consequence of its vasodilatory effects), lower plasma cholesterol and aid in bronchodilation, while Hindmarch (1988) showed that even single doses of Ginkgo extract improved short term memory in healthy volunteers. Studies of the active ginkgolides have shown anti-thrombotic activity that apears to be effected through eicosanoid modulation (Braquet et al., 1990).

Very few side effects have been reported for ginkgo extracts, and none have been serious. Mild effects have included headaches and gastro-intestinal upsets.

It is generally considered that ginkgo may have value for those suffering from occlusive vascular disorders, both peripheral and cerebral, particularly where the reduction of blood flow has resulted in decreased function.

The antioxidant properties of the herb may also result in scavenging of free radicals and thus reduction in tissue damage associated with these agents (Barth et al., 1991; Otamiri and Tagesson, 1989; Pincemail et al., 1989). Free radical damage to the body is considered by some experts as a major contributor to the aging process.

Oriental Ginseng (Panax ginseng).

In China, the word ginseng is directly translated as "the essence of man", and it is sometimes referred to as a "Dose of Immortality". It is the most valued herb used in China, and is also widely used in other Asian countries. According to the Ben Cao Chien (attributed to the Emperor, Shen Nung, circa 3100 B.C.; substantially revised and enlarged by Li Shih-Chen, 1596), ginseng is able to "support the five visceral organs, calm the nerves, tranquilize the mind, stop convulsions, expunge evil spirits, clear the eyes and improve the memory". Modern research (Liu and Xiao, 1992) has shown that ginseng contains a large number of active agents, acting on the central nervous system, cardiovascular system, endocrine secretion, immune function and metabolism, and that it also possesses biomodulation, anti-stress and anti-ageing activities.

The active principles (ginsenosides) are present in highest concentrations in the roots, and concentration increases with the age of the plant. Roots are harvested preferably from plants which are 4 years or more old. The ginsenosides have the general structures:

While the total spectrum of activity of ginseng makes it a desirable herb for use as a general tonic, it also possesses some specific activities of value in both weight loss and sports nutrition.

Ng and Yeung (1985), for example, showed that it had insulin-like activity, or at least increased insulin secretion, thus facilitating the passage of metabolic substrates (sugars, free fatty acids, amino acids) across membranes. Huang (1993) also reports that ginseng increases cellular levels of cyclic adenosine monophosphate (cAMP) in some tisses, and promotes the oxidative phosphorylation of carbohydrate secondary to insulin release. These mechanisms would explain the metabolic enhancement often reported for ginseng. Other effects of value in nutrition include a cardiotonic effect (improved cardiac function), cerebral and coronary vasodilation, increased red cell production, possible antithrombotic action, and both blood pressure and blood cholesterol lowering effects (Huang, opus cit.). These effects only become significant with longer periods of administration, but acute administration of ginseng has been shown to prolong the survival of oxygen-depleted rats, indicating an increased efficiency of oxygen utilization in metabolic processes (Huang, opus cit.).

Green Tea (Camellia sinensis):

The Tea plant originated in China, where it has been used for over 5000 years as an invigorating and healthy drink. Tea can basically be classified as white, green or black. All consist of the leaves and smaller stems of the plant. White Tea, however, is basically unprocessed and as picked, though it may be dried. Green Tea is dried for a longer period of time, and undergoes some oxidation, without, however, significant effect on the methylxanthines and catechins it obtains. Black Tea, however, is fully oxidised and the catechins have accordingly been modified. While Green Tea and its extracts do contain methylxanthines, particularly caffeine, described above in the section on Guarana, it also contains antioxidants called polyphenol catechins, the main one of which is epigallocatechin gallate, generally abbreviated as EGCG, a powerful antioxidant:

In addition to ECGC, Green Tea and its extracts also contain free catechins and gallic acid, which are also effective antioxidants.

The properties of the caffeine contained in the Green Tea extract are discussed in the section on Guarana. During the last decade, much attention has been paid to the antioxidant properties of Green Tea. While “black” tea does contain virtually the same substances (Robinson et al., 1997), the antioxidant levels are lower than in Green Tea (Langley-Evans, 2000). ECGC (epigallocatechin gallate) is the main contributor to the anitoxidant properties. The antioxidant substances are readily absorbed and can significantly increase antioxidant avtivity in blood (van het Hof et al., 1999; Leenen et al., 2000).

Epidemiological studies have indicated close correlations between use of Green Tea and reduced mortality from a number of “diseases of civilization”. The strongest correlation reported was between Green Tea use and reduced risk of death from cardiovascular events (Kuriyama et al., 2006), though a benefical reduction of mortality from all causes was reported, particularly in women. The effect on mortality from cancer was not significant, though animal studies and theoretical considerations suggest that the incidence of at least certain types of cancer may be reduced by catechins from Green Tea (Zaveri, 2006; Cooper et al., 2005b). Benefits of Green Tea in cardiovascular disease have also been signalled by Cooper et al. (2005a).

Wolfram et al. (2006) comment on the traditional notion that Green Tea consumption benefits health and that the areas of cardiovascular disease and cancer have been subject to numerous studies. These Authors note that the anti-obesity effects of Green Tea are being increasingly investigated in cell, animal, and human studies. Green Tea, Green Tea catechins, and epigallocatechin gallate (EGCG) have been demonstrated in cell culture and animal models of obesity to reduce adipocyte differentiation and proliferation, lipogenesis, fat mass, body weight, fat absorption, plasma levels of triglycerides, free fatty acids, cholesterol, glucose, insulin and leptin, as well as to increase beta-oxidation and thermogenesis. Adipose tissue, liver, intestine, and skeletal muscle are target organs of Green Tea, mediating its anti-obesity effects.

Studies conducted with human subjects report reduced body weight and body fat, as well as increased fat oxidation and thermogenesis and thereby confirm findings in cell culture systems and animal models of obesity. However, they caution that more clinical work is required to confirm many of these findings.

Siddiqui et al. (2004), and Cabrera et al. (2006) also review the numerous health benefits that appear to be derived from consumption of Green Tea, referring to recent human studies which suggest that Green Tea may not only contribute to a reduction in the risk of cardiovascular disease and some forms of cancer, but also to the promotion of oral health and other physiological functions such as anti-hypertensive effect, body weight control, antibacterial and antivirasic activity, solar ultraviolet protection, bone mineral density increase, anti-fibrotic properties, and neuroprotective power.

It is generally conceded that while most of the benefits attributed to Green Tea relate to the antioxidant components, some may be due to other substances, such as theanine (Cooper et al., 2005a), which may exert beneficial actions unrelated to antioxidant effects. In fact, the cholesterol-lowering effects of Green Tea may be due to oxidized catechins, that is, catechins which have already exerted their antioxidant actions and are no longer active as antioxidants. It has also been suggested for many years that biological antioxidants play important roles in retarding the process of aging and degenerative conditions, and it may be speculated, for example, that the protective effects of the Green Tea catechins against cardiovascular diseases may be due to prevention of oxidation of low density lipoproteins (LDL), since LDL oxidation reduces the biological functionality of the LDL fraction and may result in lipid deposition in arterial walls.

St. John’s Wort (Hypericum perforatum).

St. John's wort has long been known in traditional medicine as a urinary tract and topical antiseptic. Various Herbal Pharmacopoeias describe it as analgesic and antiseptic when applied to the skin and sedative and astringent when taken orally (BHP, 1983), and the cited reference also notes the specific indication of "menopausal neurosis".

More recently, the analysis of clinical trials involving more than 1,700 outpatients has revealed that St. John's wort, given for four to eight weeks' duration, is a safe and effective herb for the treatment of mild to moderate depression and anxiety. The main advantage of St. John's wort is the very low risk of side effects (about 20 to 50 percent of patients using tricyclic antidepressants experience adverse side effects; nausea, dizziness, fatigue, sedation, reduced sexual drive, headaches, dry mouth, and loss of appetite). Those taking St. John's wort, however, experience significant improvement in depressive mood indicators such as feelings of sadness, hopelessness, helplessness, and fearfulness, but essentially without side effects (Fugh-Berman and Cott, 1999; Kim et al., 1998; Snead and Jackson, 1999).

While it was originally thought that the mechanism whereby St. John's wort improved depressive states was based on inhibition of mono-amine oxidase, no evidence of this has been presented, and current research results point at some involvement in serotonin metabolism or function, possibly inhibition of re-uptake, as the main mechanism of action (Bennett et al., 1998; Müller et al., 1998; Perovic and Müller, 1995). Since substances which increase availability of serotonin in the so-called "satiety centre" may be effective in helping reduce food intake, it is probable that St. John's wort also shares this property.

St. John's wort contains several active components, the main ones being hypericin, pseudohypericin and hyperforin:

It is now believed that hyperforin is the main active substance in terms of antidepressive and appetite modification activities (Müller et al., 1998).

Alpha-amylase inhibitor (Phaseolus vulgaris):

The enzyme α-amylase found in the duodenum of the gastrointestinal tract acts upon large linear polymers at internal bonds. The hydrolytic products have an α-configuration. Specifically, α-amylase catalyzes the hydrolysis of internal α-1,4-glucan links in polysaccharides containing 3 or more α-1,4-linked D-glucose units, yielding a mixture of maltose and glucose. Amylolytic activity is present in all living organisms, but the enzymes vary remarkably, even from tissue to tissue within a single species.

A protein fraction from various plants, though usually prepared from beans (particularly Great Northern and red kidney beans), is capable of inhibiting the action of α-amylase in vitro. As prepared from red kidney beans, this protein fraction is a glycoprotein with a molecular weight of 49,000 (Houglam and Chappell, 1984). It is destroyed by acid (pH < 3.0) and by chymotrypsin (a proteolytic enzyme present in the duodenum), but not by pepsin (a proteolytic enzyme present in the stomach) or trypsin (a proteolytic enzyme in the duodenum) (Andriolo et al., 1984). It has also been noted that the protein may be readily oxidized. Other researchers have identified two slightly smaller glycoproteins (molecular weight about 43,000 with amylase-inhibiting actions (Le Berre-Anton et al., 1997).

Initial clinical studies gave disappointing results. For example, Bo-Linn et al. (1982) showed no effect on faecal calorie excretion after administration of a commercial "starch blocker", while Garrow et al. (1983) failed to show any changes in insulin or blood sugar levels after administration of two different commercial "starch blockers". Carlson et al. (1983) also failed to show effects on blood glucose, insulin or breath hydrogen after administration of a commercial product with verified in vitro activity.

Granum et al. (1983), however, determined that actual amounts of α-amylase inhibitor present in one commercial "starch blocker" product, though capable of inhibiting α-amylase in vitro, were too small to exert an effect in vivo, and that the degree of concentration or purification of the α-amylase inhibitor was apparently minor (to the extent that one tablet contained no more protein than a single bean).

Hollenbeck et al. (1983) came to the conclusion that while commercial "starch blockers" might inhibit pancreatic amylase, they appeared to be ineffective against the amylolytic enzyme present in the brush border cells lining the small intestine, which though it performs the same actions is in fact a different enzyme.

Later studies (Layer et al., 1984; Rosenfeld et al., 1984; Layer et al., 1985; Layer et al., 1986) showed that α-amylase inhibitors from beans were effective in preventing starch digestion in vivo if they were sufficiently purified. For example, administration of a concentrated α-amylase inhibitor with increased activity substantially reduced increases in plasma glucose and insulin after a test meal containing starch in both normal subjects and in those with diabetes (Layer et al., 1986).

Umoren and Kies (1992) tested a commercially available starch blocker derived from soybeans in rats fed potato starch, and though they demonstrated a small but non-significant decrease in body weight over a 4-week period, they did show significant increases in faecal copper and zinc excretion, the reason for which was not apparent but may have related to some degree of impairment of starch absorption. Further animal studies (Tormo et al., 2004) have now shown that the alpha-amylase inhibitor from Phaseolus vulgaris is both hypoglycemic and anorexigenic in rats, and the structure of the complex the inhibitor forms with the enzyme has been determined (Nahoum et al., 2000; Santimone et al., 2004).

In retrospect, it appears that many of the commercial "starch blockers" available in the early 1980's contained essentially unconcentrated bean protein and had little intrinsic activity, such that they could be predicted to be ineffective. Use of more highly concentrated material, however, did give clinically significant results. The sensitivity of the α-amylase inhibitor to acid, and possibly also to atmospheric oxygen, also indicates that the time of administration, and the sophistication of the formulation containing the inhibitor, are critical to the achievement of a significant degree of "starch blocking".

It should be understood, of course, that even when all these criteria are satisfied, "starch blockers" can only work when the diet contains starch; they have no effect on the absorption of simple sugars. In this respect, it has been reported that starch provides from 500 to 700 kilocalories per day in the average American adult diet.

In practice, therefore, to be effective a "starch blocker" must meet the following criteria for content and use:

  • It must provide, per serving, at least 350 mg of a highly concentrated fraction of bean protein with a high specific α-amylase inhibiting activity.

While in vitro tests may indicate, for example, that an α-amylase inhibitor is capable of inhibiting the hydrolysis of as much as 1.5 grams of starch per mg of inhibitor over a relatively short period of time, it is unlikely that activity will reach more than a fraction of this level under in vivo conditions.

However, even when in vivo activity is only 2% of the in vitro level, inhibitor of this potency can still reduce availability of many grams of starch.

  • It must be formulated in a tablet with antioxidant protection.

Exposure of the inhibitor to atmospheric oxygen is likely to result in severe loss of activity, therefore capsules are an inappropriate vehicle.

  • The tablet should have a disintegration time of more than 15 minutes, and the serving should be taken 10 - 15 minutes before the meal.

It is essential that the inhibitor is not exposed to gastric acid before admixture with the food, and it is also essential that the inhibitor passes into the duodenum together with the food. The objective is to inhibit the effect of pancreatic amylase on the starch in the meal, and for this purpose, the inhibitor must be present when the starch is first exposed to the pancreatic amylase.

  • The meal has to contain some starch, otherwise there will be no effect.

The inhibitor only prevents the enzymatic hydrolysis of the starch (amylolysis), and NOT the absorption of simple sugars.


Chitosan, a deacetylated chitin made from the shells of crustaceans, is a widely available dietary supplement that speculatively decreases body weight and serum lipids through gastrointestinal fat binding (Kaats et al., 2006).

The actual fat-binding ability of chitosan may depend on the physical form of the chitosan when it enters the small intestine, and this in turn depends to a considerable extent on the methods used in the manufacture of the material, including the extent to which the original chitin has been deacetylated. It is clinically well tolerated (Ylitalo et al., 2002), but effects are modest (Mhurchu et al., 2004). Those who are allergic to shellfish may be advised to avoid chitosan, since processing of the raw chitin may not necessarily remove all allergens.

Senna (Cassia senna).

The leaves of Cassia senna contain substances known as anthraquinone glycosides. There are four of these, known as sennosides A, B, C and D, all of which are active as stimulant laxatives. They differ only slightly in structure. After ingestion, the sennosides pass unchanged into the colon where bacteria hydrolyse the glycoside bond yielding the free anthraquinones which have direct stimulant effects on the myenteric plexus, resulting in smooth muscle activity and thus defaecation.

Essential fatty acids.

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