Monday, October 20, 2014

L-Cysteine as a Satiety Trigger: Sign. Ghrelin & Appetite Suppression in Rodents & Humans - Which Foods Are High in Cysteine & Will They Really Help You Lose Weight?

Egg whites are among the best dietary sources of cysteine
You've read about the satiety effects of several amino acids, like arginine, lysine and glutamic acid, about which you've read approximately one year ago right here at the SuppVersity (learn more). That cysteine, an semi-essential amino acid that can be biosynthesized in humans from methionine, would have the same effects, however, is news - even for seasoned SuppVersity veterans.

The news comes right from laboratories of London's King's and Imperial College, where McGavigan  and colleagues investigated the effects of oral and intraperitoneal administration of a range of amino acids on food intake in rodents.
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In their preliminary studies, McGavigan et al. identified l-cysteine, a conditionally essential amino acid that acts as a precursor for biologically active molecules such as hydrogen sulphide (H2S), glutathione and taurine, as an anorectic agent. Needless to say that they felt inclined to further investigated the effects of l-cysteine on appetite in rodents and humans and the mechanisms mediating these effects.
Figure 1: The effect of oral administration of L-andD-cysteine in rats (left) and the effect of intraperitoneal (middle)
and oral (right) administration of L-cysteine on 0–1-h food intake during the early light phase after an
overnight fast in male in male C57BL/6 mice (McGavigan. 2014)
As you can see in Figure 1 the administration of different dosages of l-cystein, but not d-cysteine (Figure 1, left), lead to a significant reduction in 0–1-h food intake in the early light phase following an overnight fast. This effect was identical, but required higher dosages of l-cysteine (human equivalent 0.036 or 0.072g/kg when it was administered orally vs. via intraperitoneal injection.
Where do you find cysteine in foods? Egg whites, whey protein (concentrate, Bounous. 1989) beef and milk are the best sources with 1.2g, 1.15g, 1.0g, and 0.72g per 200kcal serving. Cottonseeds, sprouted lentils, soy protein isolate and defatted sunflowers flour are top sources for vegetarians with 0.7g, 0.65g, 0.63g and 0.58g cysteine per 200kcal serving (nutritiondata.com).
Figure 2: L-cysteine suppresses plasma acyl ghrelin levels in rats. Plasma levels of (a) acyl ghrelin and (b) l-r: GLP-1 and PYY, 30 min after oral gavage of water or 4 mmol/kg l-cysteine (n=7–8), (c) acyl ghrelin and (d) l-r: GLP-1 and PYY, 30 min after intraperitoneal administration of saline or 2 mmol/kg l-cysteine (McGavigan. 2014)
Next to the effects on food intake, the rodent study revealed that an increase in respiratory exchange ratio (=more CHO vs. FATs were burnded) and an increases neuronal activation in the rat brainstem without negative behavioral side effects. What the researchers did not observe, though, was an a reduction in gastric emptying that would be the most straight forward explanation for the reduction in food intake. Against that background, the reduced levels of the hunger hormone ghrelin (see Figure 2) appears to be the most likely mechanism by which the l-cysteine gavage may have lowered the animals' food intake.

This hypothesis is supported by the fact that l-cysteine didn't reduce the food intake of the gen. modified mice which overexpress ghrelin (data not shown in Figure 2).
The effects remain significant with repeated administration: Even when the "trick" is repeated thrice daily for five days, the administration of l-cysteine still lead to an acute reduction in food intake and a corresponding decrease in the cumulating food intake over the 5-day study period in rodents - in view of the short study period obviously without reductions in body weight.
Now we all know that mice are no little men. Therefore, the important question that's rightly preying on your mind now is: Did this work in humans, as well? The answer is pretty straight forward: Yes, it did!
Figure 3: 0.07g/kg l-cysteine in 200ml water lead to significant reductions in hunger ratings and acyl-ghrelin in humans as the corresponding dose in rodents (McGavigan. 2014)
As you can see in Figure 3, the administration of either "vehicle" (=placebo) alone or the same 200 ml drink containing 0.07 g kg/1 l-cysteine in a single-blind (participant) randomised order lead to similar decreases in acyl-ghrelin (hunger hormone) and hunger ratings in the healthy men and women who participated in McGavigan's study.
If you haven't done this, already, it's time to check out the results of the previously cited study by Jordi et al. (2013), now | learn more
Bottom line: Luckily, McGavigan et al. did all the work for me and compared the effects of cysteine in the study at hand to the previously reported effects of arginine & co, I referenced in the introduction and found that "l-cysteine is more anorectic than l-arginine and l-lysine." (McGavigan. 2014)

Furthermore, the researchers point out that "[i]f l-cysteine does have a physiological effect on appetite, then it is likely to act in concert with other products of protein digestion, and thus the effects of l-cysteine per se may be difficult to detect." (McGavigan. 2014) In other words, the repeatedly demonstrated satiety effects of high protein diets may - in parts - be mediated by their cysteine content.

In view of the fact that the effects occur at dosages that do not trigger taste aversion or evoke abnormal behaviour, it may even be possible to administer l-cysteine supplements to overweight individuals before every meal to reduce their food intake and trigger (probably) slow, but persistent weight loss. Since the real-world food intake wasn't measured in humans, yet, this would have to be confirmed in future trials, though | Discuss this article on Facebook!
References:
  • Bounous, Gustavo, Gerald Batist, and Phil Gold. "Immunoenhancing property of dietary whey protein in mice: role of glutathione." Clin Invest Med 12.3 (1989): 154-61.
  • Jordi, Josua, et al. "Specific amino acids inhibit food intake via the area postrema or vagal afferents." The Journal of physiology 591.22 (2013): 5611-5621. 
  • McGavigan, A. K., et al. "l-cysteine suppresses ghrelin and reduces appetite in rodents and humans." International Journal of Obesity (2014).