DHEA [BSA]

Dehydroepiandrosterone sulfate (DHEAS) is an organic, sulfated steroid hormone. It's the sulfate ester of dehydroepiandrosterone (DHEA), produced mostly by the adrenal glands, but also by the gonads and the brain. DHEAS is one of the most abundant, especially in the bloodstream, steroid hormones in the human body, as well as the forerunner to many other hormones including testosterone and oestrogen. It's highest in the early adulthood and lowest with age, making it a useful determinant of ageing and disease. DHEAS is also unlike any other hormone in the capacity to modulate an extensive array of biological functions including immune function, metabolism, and cognitive function. Yet for all its ubiquity and potency, DHEAS tends to be sidelined behind the more popular derivatives, whether that's DHEA or the sex hormones it plays a role in generating. Among the most notable features of DHEAS is the fact that its levels in the bloodstream peak early in life, and then begin to drop off as you age (this is known as "DHEAS decline"). It has been linked to various diseases of old age, such as heart disease, osteoporosis and cognitive decline. DHEAS doesn't shift like other steroid hormones that do when they're tied to the circadian rhythm or to the timing of menstruation – which makes it a desirable candidate for ageing and hormone treatments. The body's DHEAS levels can be influenced by multiple factors such as genes, lifestyle, and the surrounding environment (food, stress, etc. Second, it has a protective function against aging and disease, which has attracted much scientific attention in research into ageing and DHEAS modulation interventions. The biochemical circuits of DHEAS are complicated, and science still finds fascinating new information about how it functions. As a prohormone, DHEAS is converted into active hormones such as testosterone and oestrogen that function within the reproductive and endocrine functions of the body. But DHEAS itself also has measurable immediate effects. DHEAS has neuroprotective properties – that it regulates brain function and can impact mood and cognition. This by activating brain neurotransmitter and neurosteroid receptors. Moreover, DHEAS has also been found to regulate metabolism, such as insulin resistance and fat metabolism, hence it could have an effect on obesity and metabolic syndrome. These multiple consequences make DHEAS an important biomarker for scientists studying ageing, metabolic health and brain ageing.

Figure 1. Schematic representation of converting dehydroepiandrosterone sulfate (DHEAS) into testosterone and estrogen. (Sources: Jayarathna DK, et al. 2022)

DHEAS is a steroid hormone, so it's commonly talked about when it comes to old age and longevity. Its progressive drop as you grow older inspired researchers to examine the relationship between DHEAS and many diseases of ageing. There's now evidence that DHEAS might even help protect against the most common age-related diseases — osteoporosis, heart disease and dementia. Researchers have proposed, for instance that those with greater DHEAS might suffer a slower bone-density loss, reducing their vulnerability to fractures and osteoporosis. DHEAS may has been positive for the heart by strengthening endothelial cells, lowering inflammation, and reducing the of atherosclerosis. How, still not determined, but DHEAS's ability to regulate lipid metabolism and inflammation could be another reason your heart is in good hands. Neuroprotective effects of DHEAS were also hot topic in recent years. DHEAS is an active neurosteroid, so it can have a biological effect on the brain through changes in networks of neurotransmitters and plasticity of synapses. Others have even suggested that DHEAS – and excess levels of it – could be associated with lower risk of neurodegenerative disorders like Alzheimer's and Parkinson's. In animal studies, DHEAS also improves cognition, anxiety and perhaps even retards neurodegeneration in old age. Whether DHEAS can help patients in the neurological space is something researchers are still working on – particularly when it comes to dementia and related mental illnesses. There's also been research on DHEAS as a mood regulator, and reduced DHEAS has been shown in some clinical trials to correlate with depression and anxiety. And DHEAS has been linked to all manner of metabolic diseases. The hormone is thought to modulate insulin-sensitivity and glucose metabolism, and perhaps that's why some researchers identified low levels of DHEAS as an indicator of metabolic syndrome, type 2 diabetes and obesity. The exact connection between DHEAS and metabolic health remains under active research, but the hormone is believed to control fat metabolism, fat oxidation and insulin resistance. These effects make DHEAS potentially therapeutic for the treatment of obesity and metabolic disease, although it will be some time before we know in clinical trials exactly what it is doing.

DHEAS has also emerged as an option as part of hormone replacement therapy (HRT) over the past few years – particularly for people in their 50s or 60s with a hormone depletion. While other steroid hormones, such as estrogen and testosterone, also do, DHEAS isn't quite as hormonally destabilizing or detrimental to the patient during therapy. Other supporters of DHEAS therapy say that restoring it would combat the signs of old age: low libido, muscle numbness, fatigue. Actually, DHEAS supplementation has been tested in a handful of clinical studies for increased energy levels and exercise performance, particularly in the elderly. But even with encouraging results, supplementation with DHEAS is still controversial, and its effects are unclear after the fact. Reviewers who denounce DHEAS therapy draw attention to the fact that there is little agreement about whether or not it's safe and effective, particularly in terms of its effect on the hormones: the body's own hormonal balance is a complex dance between various steroids, and taking DHEAS may override that delicate dynamic, and the consequences can be dangerous. And you also have the possibility of getting some cancers, including hormone sensitive cancers (breast, ovarian, prostate), even after you've tweaked steroid hormone levels. DHEAS supplementation research is still rudimentary and some studies are positive, others have reported almost no benefit. DHEAS treatment, therefore, is a field of active research, and researchers are trying to unravel its therapeutic and safety profile.

Dehydroepiandrosterone sulfate
Prasterone
Androstenolone
3β-Hydroxyandrost-5-en-17-one
DHEA sulfate