A recent survey  focusing on weight loss has drawn attention on ephedrine: a research team at Joslin Diabetes Center have tried to find new ways to activate brown fat and thought that ephedrine might be a potential triggering agent, due to its known effects on the sympathetic nervous system, such as the famous “fight or flight response“.
Before going to the conclusion of this study, it might be useful to give some basic information about brown fat and how it can lead to weight loss.
What is brown fat?
Brown fat is the common name for Brown Adipose Tissue (BAT), also known as “good fat”. Brown fat has been initially classified as an adipose tissue because of it is storing lipids, but recent findings showed that it is in fact closer to muscle than to white adipose tissue. The main function of brown fat is to produce heat in a process called non-shivering thermogenesis. The exceptional thermogenic characteristics are due to the high number of mitochondria which are specialized cells transforming fatty acids into energy and heat.
How does brown fat work?
Brown fat is linked to the brain by the sympathetic nervous system and activated through the release of norepinephrine. Then a complex chemical process begins: triglyceride breakdown, release of fatty acids which enter the mitochondria and are degraded through ß-oxidation, followed by CAC (citric acid cycle) and activation of UCP1, a protein uncoupling mitochondrial respiration from ATP, producing heat. To make it easy: the activity of brown fat is regulated by the brain through the sympathetic nervous system in case heat is needed for body temperature control.
Where is brown fat located in the body?
Unlike white fat which is usually located in hips, belly etc (android and gynoid fat), brown fat is mainly found in the neck and below the clavicles, but this may vary a lot depending on age, gender, weight, etc.
Do adults have brown fat?
Until recently, the scientific community was convinced that brown fat was present in newborns only. In the 1990s, PET scans of cancer patients showed unexpected areas of tissues with a high glucose uptake. Unfortunately this finding found no echo outside of the radiology profession and only in 2002 the link with brown adipose tissue has been envisaged. At this time, the common belief was that brown fat was to be found in only 2 to 5% of adults. Further research has proved that at least 30% of all adults possess brown fat and probably 100% of young adults.
Brown fat is drawing attention because of potential weight loss effects: we know since the research conducted by Ouellet et al  that brown adipose tissue in adults is burning fat actively when stimulated by cold exposure, through the combustion of stored lipids within brown fat in the initial phase and in case of prolonged thermogenesis, through the combustion of the components of ingested food, involving gut and liver. As brown fat burns calories to generate heat for defense against cold, it became interesting to the weight loss industry:
- A first approach is to work on metabolic pathways which make white fat cells act like brown fat cells and enable them to release energy as heat .
- A second approach is to work on the activation of brown fat: to the current knowledge this is only possible during cold exposure, the idea is thus to identify agents which have the same pathways and mimic cold in brown activation.
How does it relate to ephedrine?
There are two links: the first one is that brown fat is triggered by the sympathetic nervous system through the release of norepinephrine, which is very close to the physiological effects of ephedrine and that is why many researchers thought that ephedrine might be a good candidate of brown fat metabolic activation. The second reason why ephedrine has been compared separately to brown fat effects is that ephedrine is considered as one of the most effective fat burner, therefore it has been used as a reference to measure the weight loss results obtained through brown fat activation alone.
What protocol has been used for this study?
The study conducted by the Joslin team has tested ten healthy adults in three ways:
- injections of ephedrine
- injections of a control saline solution (placebo)
- wearing water-cooled 57F (14C) vests for two hours
Each intervention was followed by PET/CT scans in order to measure the consequent brown fat activity.
What are the results of this survey?
The main findings are the following:
- Ephedrine did not turn on brown fat: there was no difference in BAT activity compared to placebo injections.
- Cold exposure did stimulate brown fat energy expenditure significantly.
- Ephedrine and brown fat activity have different sympathetic pathways: both increased blood pressure and energy expenditure, but ephedrine raised also heart rate and the circulation of various metabolites (insulin, glucose, thyroid hormones) when cold brown fat activation decreased heart rate and had few effects on metabolites.
- Regarding weight loss effects, ephedrine and brown fat activation resulted in the same number of calories burned during both programs.
According to the researchers, brown fat activation is promising because it can achieve the same weight loss results as ephedrine with less systemic effects. Another study is already planned with subjects wearing water-cooled vests for several weeks. More research will tell if weight loss resulting from brown fat stimulation can be reasonably achieved through cold, or if the pharmaceutical industry should try to identify other agents that would mimic cold activation of brown fat. For sure, wearing cooling vests for a long time would be very uncomfortable and overweight people are probably not ready to accept such discomfort.
Of course researchers show enthusiasm for their findings when they might help combat obesity, knowing the financial attractiveness of the weight loss market. Most experts think that no magic pill will come from the current pharmaceutical research for the next ten years. Any discovery in the weight loss field sets off fireworks in the industry, and this has also been the case when this study has been published.
According to Dr Aaron Cypess, lead author of this survey: “The problem with prescribing ephedrine is that people need to stay healthy their whole lives. Are we really going to be prescribing a sympathetic activating drug for someone’s entire life? There need to be safer, long-term solutions“.
We don’t agree with this point of view. Of course people need to stay healthy, but overweight people (no even speaking of obese people) have to get healthy again before staying healthy! Ephedrine can help them in countries where sales are authorized for weight loss, due to its synergetic effects on appetite, metabolism, energy and lean muscle mass retention: ephedrine will help shed the pounds when they are not able to lose weight without a physiological boost at start. The idea is not to buy ephedrine for years, but to burn fat rapidly and to keep it off definitely without drug support, by a change in lifestyle, such as eating better and being more active. As a comparison, many smokers stopped definitely only with the initial support of nicotine patches. Do they have to use nicotine patches for the rest of their life? Of course not. The same applies to weight loss obtained through initial support of ephedrine.
 Cypess A, et al. Cold but not sympathomimetics activates human brown adipose tissue in vivo, PNAS USA Early Edition 10.1073/pnas.1207911109
 Ouellet V, et al. Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J Clin Invest. 2012;122(2):545–552
 Plutzky J, et al. Retinaldehyde dehydrogenase 1 regulates a thermogenic program in white adipose tissue, Nature Medicine 18, 918–925 (05/06/2012) 10.1038/nm.2757
By Mike Budd