Chemically, ephedrine found in herbs such as Ma Huang (Ephedra sinica) is a phenylethylamine compound structurally similar to amphetamine, belonging to the class of sympathomimetic protoalkaloids¹

Sympathomimetic compounds mimic the action of adrenaline (epinephrine)-like neuro-transmitters at peripheral sympathetic neurons and also exert central nervous system effects.

Adrenaline systems control important body functions like blood pressure regulation and wakefulness.

Ephedrine has a₁ a₂ b₁ b₂ adrenergic receptor-agonist properties³. 40% of the thermogenic activity of ephedrine is reported to be due to the activation of the b3 adrenoreceptors in the adipose tissues². Ephedrine also stimulates thyroid functions.

Ephedrine is referred to as a mixed-acting drug because it activates adrenergic receptors by direct and indirect mechanisms. Direct activation results from binding of the drug to alpha and beta-receptors. Indirect activation results from release of noradrenaline from adrenergic neurons³.

Chemically, forskohlin found in Coleus forskohlii is a labdane diterpene¹.

It is a direct activator of the enzyme adenylate cyclase which is involved in the generation of cyclic adenosine monophosphate (cAMP)⁴. Forskohlin also stimulates thyroid functions.

cAMP is a "second messenger" hormone signaling system. In many hormone sensitive systems the hormone itself does not enter the target cell, but binds to a receptor and indirectly affects the production of another molecule within the cell, which then diffuses intracellularly to the target enzymes or a receptor inside the cell to produce the response. This intracellular mediator is called the second messenger.

cAMP, and therefore forskohlin, have marked physiological effects through such "second messenger" actions on various biochemical processes in the body.

• activation of hormone sensitive lipase is linked to cAMP
• forskohlin bypasses the adrenergic receptors activation step, increasing cAMP levels directly.
• The beneficial effects of forskohlin, therefore, do not depend upon the sensitivity of the adrenergic receptors which can often decrease with age and other physiological factors. forskohlin has also been shown to counteract the decreased response of fat cells to epinephrine, associated with aging.
• The mechanism of action of forskohlin does not involve non-selective binding to the adrenergic receptors. Therefore, forskohlin does not produce the unwanted side effects associated with their activation.
• forskohlin, when administered in the form of ForsLean®, a patented proprietary extract standardized to contain 10% forskohlin, increased lean body mass in test subjects while simultaneously reducing body fat and weight10, thereby helping to optimize body composition.

Since ephedrine activates the same adrenergic receptors as epinephrine, these drugs share the same adverse effects³.

Hypertension (increase in blood pressure), due to constriction of the peripheral blood vessels (vasoconstriction)

Dysrhythmias (increased heart rate due to cardiac stimulation)

Angina (chest pain due to depleted oxygen in the heart muscle)

Hyperglycemia (increase in blood sugar levels)

Ephedrine use is therefore contraindicated in people prone to hypertension, heart disease, hyperglycemia, hyper- thyroidism, prostate disease and related conditions and in those taking prescription medications^3,6.

Care should be taken to avoidadministration of ephedrine with other stimulants such as caffeine⁷.

The mechanism of action of forskohlin does not entail the activation of adrenergic receptors.

Forskohlin is a known blood pressure lowering agent and is used in the management of hypertension, including ocular hypertension that leads to glaucoma⁴.

Preliminary studies in humans have shown that forskohlin increases the contractility of the heart muscle without increasing oxygen consumption and that it is a vasodilator^4,8.

Forskohlin has been shown to inhibit platelet aggregation further validating its beneficial cardiovascular effects⁹.

Clinical studies revealed that forskohlin, in the patented ForsLean® composition, in daily doses of 50 mg for 12 weeks, did not cause adverse effects on the systolic/diastolic blood pressure and the pulse rate¹⁰.

Forskohlin is known to regulate the secretion of insulin, thereby helping to maintain healthy blood sugar levels¹¹.

Forskohlin, in the patented ForsLean® composition, had an LD50 greater than 2000 mg/kg and may therefore be considered safe for use by most healthy people¹².

As with all other supplements, people taking medications for asthma, hypertension, hyperthyroidism and related conditions as well as those suffering from ulcers or low blood pressure conditions should exercise caution¹³ and seek medical supervision.