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Full study on Yohimbine and Fatloss
Yohimbine and Fat Loss
Since a 2-ARs are present on adipose tissue and inhibit lipolysis, yohimbine has been proposed as a pharmaceutical approach to fat loss. In vitro results demonstrated that E, a non-selective agonist for a /b -ARs, produced less lipolysis than a selective beta-agonist (33). However, when an a 2-antagonist, such as yohimbine, was added, E induced the same rate of lipolysis as the beta-agonist. Clinical investigations report yohimbine administration (0.2 mg/kg total body weight) increases plasma levels of NEFAs and glycerol in obese and non-obese women as well as in men (26,35,36). Yohimbine increased weight loss when used with hypocaloric diets in several studies by preventing an adaptive lowering of the SNS that usually occurs with most calorie-restriction (37). Resting energy expenditure did not change in a group of obese and lean women when administered yohimbine (38). However, exercise energy expenditure in same subjects was significantly potentiated along with accompanying parameter of lipolysis
Results from many studies conclude that the primary lipid-mobilizing effect of yohimbine is stimulation of the SNS (26,34,35). A beta-antagonist was administered to non-obese and obese subjects 60 minutes before yohimbine. This suppressed the b -AR effect of lipolysis induced by increases in NE levels. Plasma NEFA levels decreased, but plasma levels of NE were unchanged (34). However, yohimbine still had a transient lipid mobilizing effect evidenced by increased levels of NEFA after b -AR blockage (34,35). These results indicate that only a minor part of the lipid-mobilizing effect of yohimbine is attributed to direct blockage of the lipolysis inhibiting a 2-ARs on adipose tissue.
Discrepancies exist in methodology used in yohimbine and weight loss research. Considering that increases in NE levels after oral yohimbine is dose dependant (39), most studies have shown optimal dosage to be 0.2 mg/kg (8). Some studies have used much smaller dosages with less significant results. Another cause of discrepancy is timing of yohimbine administration. The lipid-mobilizing effects of yohimbine are completely negated when administered with or after a meal (35). Administration of a 2-antagonists such as yohimbine increases insulin secretion during glucose stimulation. This is attributable to the blockage of the a 2-ARs on pancreatic beta-cells and to concomitant stimulation of the pancreatic beta-ARs. Yohimbine was administered to test subjects in earlier studies which caused increased insulin secretion to blunt its lipid mobilizing effects (40). However, in fasting conditions, yohimbine does not increase insulin levels. These results demonstrate the importance of nutritional status when administering a 2-antagonists as lipid-mobilizing agents.
Studies suggest yohimbine may increase vasodilation in adipose tissue. Subjects administered yohimbine showed significantly increased levels of plasma NEFA when they changed from a supine position to an upright position (26). The increase in NEFA levels observed were probably due to b -AR stimulation of lipolysis and possibly an increase in net outflow of NEFA from adipose tissue due to yohimbine-induced decrease in local vasoconstriction. When nitroprusside, a vasodilator, was infused by microdialysis, extracellular glycerol concentrations decreased and escape of ethanol increased in adipose tissue (20,24). This suggests that the escape of glycerol from the extracellular spaces in adipose tissue can be accelerated by increased blood flow. The peripheral vasodilation effects of many a a-antagonists are known. However, the direct vasodilation effects in adipose tissue by yohimbine will need to be conclusively assessed by techniques such as microdialysis.
Increased peripheral vasodilation by blockage of the blood vessel wall a 2-ARs may increase systemic distribution of lipolysis by-products. Submaximal-intensity exercise could enhance net lipolysis in combination with yohimbine administration. Microdialysis studies suggest that NEFAs accumulate within adipose tissue during strenuous exercise due to limited transport into systemic blood supply (13). Recall that exercise-induced increases in blood flow does not rise in proportion to NEFA production (41,42). Therefore, the rate of systemic NEFA delivery does not increase simultaneously with increasing intensity of exercise. Accumulation of NEFA in adipose extracellular spaces may possibly exert a feedback inhibition on lipolysis. As well, vasoconstriction may be induced by high concentrations of NEFA or high sympathetic stimulation (43). Increased peripheral vasodilation in adipose tissue effected by a 2-antagonists may enhance removal of lipolysis by-products during low- to moderate-intensity exercise. Additionally, higher systemic transport of NEFA may increase their uptake into working muscles.
Considering the research that is available thus far, it is conceivable that the optimal plan for administrating yohimbine as a lipid-mobilizing agent would be early mornings after an overnight fast and several hours before breakfast. The relatively low levels of plasma glucose would not stimulate a yohimbine-potentiated increase in insulin that would otherwise negate its lipolytic effects. Utilization of body fat stores would be optimal with low insulin levels and lipid-mobilizing stimulation of the SNS. Conceivably, yohimbine administration could be followed in two to three hours by ingestion of a high-protein, high-fat meal. Protein ingestion will cause only a transient rise in plasma glucose levels with a concomitant rise in insulin secretion. Accompanying dietary fat will slow digestion and absorption of protein in the same meal. Therefore, the resulting insulin spike will only transiently blunt lipolysis.
Most of the studies with yohimbine as adjunct treatment for weight loss report very few side effects in subjects. However, whatever the therapeutic use, side effects will occur due to the blockage of a 2-ARs on other tissues. Dosage, nutritional status, and general physiological condition of the individual can modify these side effects. Side effects may consist of skin flushing, headaches, and excitement. Men may experience an increase in or prolonged erections possibly due to increase in vasodilation in the penile tissue, which has a high density of a -ARs.
Few study subjects experienced changes in blood pressure or rise in heart rate. This may be explained by blockage of both vascular a 1/a 2-ARs and minimizes the vascular responses induced by catecholamine release (15,33,44). However, vascular changes have been reported when yohimbine administration is accompanied by exercise. Anecdotally, many people dosing with yohimbine report rapid increase in heart rate during cardiovascular (aerobic) activity. It is wise to monitor heart rate closely when combining the two.
Some individuals experience profuse sweating and increased salivation at higher doses (45,46). Yohimbine will block the a 2-ARs mediating acetylcholine and effect the cholinergic system as mentioned in the beginning of this article installment. Other side effects may include water retention and increased colon excretion (47).
Most studies reported that subjects experienced little or no side effects with single oral dosages ranging from 5-20 mg. Those studies basing dosages on bodyweight (0.2mg/kg) also reported few problems with side effects. Yohimbine administration to subjects in psychiatric research induced episodes of anxiety in individuals with pre-diagnosed anxiety disorder (48). Control subjects did not experience similar effects. Central nervous system effects are dose dependent. High oral dosages (40 mg ) and intravenous administration may significantly increase plasma E levels with resulting increase in heart rate and blood pressure (49,50).
Several contraindications exist that individuals should be aware of when considering dosing with yohimbine. As with most any a 2-antagonist, yohimbine can acutely increase blood pressure in hypertensive patients. It should also not be combined with other drugs that are known to inhibit neuronal uptake or metabolism of NE, such as some anti-depressants. Individuals should also consider the tendency of yohimbine to evoke psychiatric reactions in those who are predisposed to anxiety or panic episodes (51). Yohimbine will act synergistically with ethanol to increase alcohol intoxication by increasing NE turnover albeit through different mechanisms (52).
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