Amberen is a natural compound composed primarily of salts of succinate, a natural mitochondrial metabolite that is a component of the citric acid cycle. Given orally in tablet form, it is used to treat the adverse pathological symptoms of menopause by stimulating the hypothalamic-pituitary-ovarian axis to revive its production of estrogen.

Amberen was launched in the United States in September 2007 for use in perimenopausal and menopausal women who experience menopausal symptoms as a result of age or surgery (eg, hysterectomy). Recent clinical and animal studies¹ have demonstrated the efficacy of Amberen in improving the physical, biochemical, psychological, and neurovegetative symptoms associated with menopause.² Currently, a large-scale, early-stage clinical trial is being planned to further study the safety and effectiveness of Amberen in treating osteoporosis.

Amberen was developed at the Russian Academy of Sciences and is marketed by US-based Lunada Biomedical, Inc.

Background

Succinate is a potent physiological regulator that catalyzes the conversion of renin to angiotensin in connection with adrenalin and noradrenalin synthesis.^3,4 Furthermore, succinate can stimulate activity of the hypothalamic-pituitary system to restore ovary function.⁵

Succinates were proposed to treat menopause as an alternative to hormone replacement therapy by restoring the depressed hypothalamic sensitivity that develops with age, a model developed by Professor Vladimir Dilman known as the neuroendocrine theory of aging.⁶ In the context of menopause, feedback between the hypothalamus and ovaries becomes impaired, causing the ovaries to cease production of hormones, thereby inducing menopausal symptoms.

Active Conformers of Succinate

Succinates used in Amberen are quite unique. They are distinctly different from other succinates that are used in the pharmaceutical industry and elsewhere. Their unusually high biological activity is determined by three types of active conformers.

It has been theorized that active conformers of succinate have valuable pharmacological properties. In 1965 and 1966, two Japanese patents filed described the process of obtaining the calcium salt of a biologically active conformer of succinic acid, which had “anti-carcinogenic, cardiotonic, diuretic and deodorizing” effects.

Normally, to achieve conformational change, scientists use an elegant solution: altering the parameters of substance crystallization by modifying the temperature, pressure, solution, and, most interestingly, methods of substance synthesis. Succinic acid, however, proved to be more elusive, because under virtually every condition and parameter of crystallization, scientists were only able to yield a mix of succinic acid conformers with a prevalent low-energy component.

In 1998, a process for deriving active conformers of succinate was invented by researchers at the Russian Academy of Sciences, Institute of Theoretical and Experimental Biophysics. Biological activity of their succinate preparation was verified by conformational-spectral analysis with double-beam laser spectroscopy. Lunada Biomedical acquired the intellectual rights to this process and is presently the only company in the world producing active conformers of succinate.

Animal study

In a mouse model of menopause, Professor Eugene I. Maevsky and colleagues found that Amberen normalized the erratic estrous cycle of aging female mice to resemble that of healthy, young mice.¹ Compared with untreated animals, which experienced decreases in body weight and bone mass, old mice given Amberen did not lose as much body weight and increased the water, organic, and mineral content of bone tissue.

Furthermore, Amberen restored the activity and youthful coat in old mice, in whom spots of bald skin also eventually grew new hair.

Clinical Study

A recent clinical trial demonstrated that a four-week treatment with Amberen increased the level of estradiol fourfold in menopausal women, compared with control.1 Amberen also alleviated many neurovegetative (headache, insomnia, hot flushes), psychological (depression, anxiety), and physical (cardiac pain, muscle and joint pain) presentations of menopause.

Amberen also decreased thickness of the endometrium, which appeared more homogeneous with treatment.

Amberen is the first successful practical application of the neuroendocrine theory of aging.

Side Effects and Cautions

Amberen was not shown to cause any adverse events in animal, toxicology, and clinical studies.

Amberen is not recommended for use in any patient suffering from thyroid goiter or extreme forms of arterial hypertension.

Components:
Succinate
Glycine
Glutamate
Fumarate
Ammonium
Calcium
Magnesium
Sodium
Tocopherol acetate


References

1.