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Stress, hunger, leptin and BMI
01 Feb 2014, 23:57
I've just come across this very interesting paper about leptin (a hormone that controls appetite: low leptin stimulates appetite). It's not that recent a study but I believe it offers a bit of an insight into what may be happening for some people.

We have studied the effect of food and fasting on circulating leptin levels in 20 subjects of normal body mass index (BMI range 18-25) and in a group of 12 moderately-severely obese subjects (BMI range 34-61). We also studied the effect of food and fasting in a patient both before and after the successful removal of a pancreatic insulinoma as a model of excess insulin secretion.
Mean leptin levels were significantly higher in the obese than in the lean group (42.7 +/- 3.41 vs 5.35 +/- 1.55 micrograms/l, mean +/- SEM; P < 0.001), and showed a positive correlation with body mass index (r = +0.71; P < 0.001). Frequent (every 20 minutes) sampling for 3 hours after food did not show any acute changes in circulating leptin levels. On the fasting day we observed a small but significant fall in circulating leptin levels in the last 4 hours of a 20-hour fast in our subjects as a group (92 +/- 0.03% of basal, P = 0.03); however, in the lean subjects the fall was greater (86 +/- 0.04% of basal, P = 0.02) than in the obese, where it did not reach statistical significance (96 +/- 0.05% of basal). Pre-meal and peak insulin levels showed a positive correlation with circulating mean leptin levels (r = +0.65; P < 0.001 and r = +0.78; P < 0.001, respectively) in all subjects, while pre-meal and peak serum cortisol levels showed an inverse relation with leptin levels (r = -0.53; P = 0.002 and r = -0.41; P = 0.02, respectively); this effect was independent of BMI in the obese subjects. In the patient with the insulinoma the markedly elevated insulin and leptin levels measured before the operation returned to normal after removal of the tumour, in accord with reports of experimental animal data that long-term insulin excess per se is associated with increased circulating leptin concentrations.
Leptin is a robust indicator of BMI and insulin levels, both basal and stimulated, but does not change acutely following food. Fasting causes a proportionately greater decline in leptin levels in lean subjects than in obese subjects. Circulating leptin is inversely correlated with the activity of the hypothalamo-pituitary-adrenal axis: whether this is a direct influence of leptin on hypothalamo-pituitary-adrenal activity, or whether both are indirect indicators of body fat stores, requires further investigation.

Fasting for 20 hours caused a drop in leptin in the last 4 hours of the fast which was greater in lean than overweight people. Leptin levels are lower when cortisol is raised.

This implies that fasting for more than 16 hours may increase appetite in lean individuals (perhaps linked to the set point idea in that the body tries to prevent weight loss when you get slim). It also implies that stress, which increases cortisol will also cause increased appetite.

I think this study provides a mechanism for the famine reaction and how it's possible to fast too much and how stress interferes with weight loss.
Stress, that big bugbear of mine, plus lack of sleep ( a cause of stress), another bug bear of mine. Its no wonder I have plateaued.
Interesting. This backs up the practical advice in that article you bumped a few days ago (the "you're not doing it right" article) where the length of the fast should be less when you do it more-often. I wonder if a 16:8 more than 3 or 4 days per week might be pushing it for some, especially if they are already lean?

Might be something to think about, carorees, as you (and I, hopefully right behind you) transition from weight loss to maintenance.
I feel that running 5:2 and 3x16:8 for a couple of months together might have played havoc with my weight loss. I wasn't thinking my losses would be massive but thought by using 16:8 as a control for my eating on normal days as was in a hungry patch , Was that famine effect kicking in even then. Maybe I would have done better with one or the other not both with the wisdom of hindsight. Also have been stressed and don't sleep well like Julie. Hope everything returns to my earlier weight loss patterns one day soon.

Very appreciative to read any research in this area
I suppose I could be considered 'lean' and I eat in a 16:8 pattern most days. Strangely enough I feel less hungry on the days when I go to the gym in the morning and could easily extend my fast for another couple of hours after I've exercised.
callyanna wrote: I suppose I could be considered 'lean' and I eat in a 16:8 pattern most days. Strangely enough I feel less hungry on the days when I go to the gym in the morning and could easily extend my fast for another couple of hours after I've exercised.

There is an inverse relationship between exercise and leptin resistance. Interesting article below: ... tance.aspx

As I understand it, leptin resistance can develop in overweight and obese people in a way similar to how insulin resistance develops. When your body becomes leptin resistant, high levels of leptin in the body will not suppress your appetite. Combined with the study results that carorees put in the OP, this suggests a natural combination of daily fasting and exercise may work very well with obese people when it comes to hunger management.

So exercise during fasting (say, just before you break a fast) is indirectly appetite suppressant in people with leptin resistance by (temporarily?) making them less-resistant to leptin's effects on appetite.

Good stuff. :grin:

Edit to add: One thing that strikes me about these things is the relationship between leptin resistance and insulin resistance. I'm sure @carorees has already made this connection through all the stuff she's posted before, but I'm a little slow on the uptake apparently. :oops:

Another edit: pasting the link to the article carorees recently bumped: ... -it-wrong/

And a quote from it:

[M]y general rule is the longer the fast the longer the recovery time that’s needed before the next fast.

My rough template looks like this:

5-7 times per week – fasts should be between 12 and 16 hours long.

3-4 times per week - fasts should be between 16 and 20 hours long.

1-2 times per week - Fasts should be between 20 and 24 hours long.

1-2 times a month – Fasts should be between 24 and 72 hours long.

Any longer than this and you’re looking at something you should do every other month at the most, and if it’s much longer than 72 hours you should consider doing so under medical supervision.
Here is another leptin article: Crave foods? Could be your leptin
I read this thread and one by BruceE(?) yesterday and suddenly lots of things made sense. I have been trying to 5:2 and 16:8 everyday and I am feeling fatigued by it all. As I am in maintainence it was all too much for me and I think 16:8 is the way to go as I don't eat breakfast now. I am feeling relieved that I have realised this as it was all becoming a bit much and I was finding that I didn't eat for ages and then crammed loads in I felt muddled. What with low carbing too it was too much to take on board. So I am simplifying and feel much relieved. :)
scubachick wrote: Here is another leptin article: Crave foods? Could be your leptin

Excellent article, thanks @scubachick!

I would add that there is some evidence that intermittent fasting can restore leptin levels. Some studies of Ramadan fasting found an increase in leptin levels after the month of daily fasting, but others found no difference. The least we can take from the Ramadan studies is that fasting itself does not appear to adversely affect leptin levels, and it might even improve them. Given the effects of fasting on lowering appetite that we have all experienced, this seems a fair conclusion to draw.

I would also say that the high protein breakfast is probably not necessary unless you are struggling with hunger issues! It is certainly worth experimenting with if you are. I might add this info to the "why am I so hungry" article I wrote: ... fast-days/
@Carorees, are you the right person to ask questions about hormones and leptin? I am approaching an age where I am becoming more aware of my hormones. I think that I read leptin is the master hormone, so a lot of the other hormone levels depend on this. Am I right in thinking this? If so, then I am wondering if, as I approach my goal weight, would my recent hormonal issues be due to low leptin, which is due to fasting? The hormone issues I am having is basically turning me into a moody teen, but I am 40, so coming out yhe other side. My moods have been a bit more erractic for the last couple of months.
I'm not sure that any hormone can rightly be called the master hormone! They all interact with each other in complex ways. Thyroid hormones are vital and are affected by weight loss and energy balance. Leptin is of course important, but I believe mainly controls hunger. The stress hormone, cortisol is also sensitive to energy balance as well as other stressors such as family and work stresses, exercise stresses, illness etc. As you lose weight you release oestrogens from the fat stores that can also affect mood. Then insulin too could have a role. So many things affect the levels of these hormones from the food you eat, the stresses you are under, how well you sleep, your age, time of month, and even the time of year!

If your problems are moodiness possibly it is an imbalance in sex hormones. The weight loss and the time of year and your age might influence this.
If your problems are hunger and cravings that is more likely to be insulin, leptin etc.
Cortisol build up can affect both.

I think the answer lies in observing your moods closely. Do you think you notice any kind of link between your moods and fasting? (Are they better/worse on fast days? Better/worse when you have eaten well? Are your moods affected by certain foods?) Think about your sleep, stress etc situation. Then maybe see if you can tweak your fasts, foods, sleep, stresses in some way to reveal whether these are the source of the problem.

Sorry not to be of more help...
That is great help, thanks @Carorees. As usual, I learned a lot from your post. :like: I have noticed that I am short tempered with the kids much more on fast days. Since starting this woe I have also experianced more pms moodiness too. That might be coincidental with things happening because of my time of life. Im just trying to figure out what is actually going on. I was with my gp today for bloods, including a hormone check, but I gather that it is difficult to say if hormones are "in balance" or "normal" because there are so many variables. High Corisol and liw serotonin may be playing a part as my insomniac kids have me up most nights :sleepy: of course, it could be my crash course in endocrinology that is keeping me up too :grin: all that study!
If you want more study, try the science section in the fasting pages!
About reducing leptin levels...

From page 182-183, Volek/Phinney "The Art And Science of Low Carbohydrate Living":

"Leptin levels in plasma are significantly increased in obesity and insulin resistance but the presence of leptin resistance prevents its normal actions (increased energy expenditure, decreased food intake, increased muscle and liver fatty acid oxidation). We recently showed a marked reduction
in leptin in response to a low carbohydrate diet (-42%) compared to a low fat diet (18%)[56]
. The greater decrease in Ieptin concentration persisted after normalization of values to account for the greater reductions in body mass and fat mass in the subjects consuming a low carbohydrate diet, suggesting an improvement in Ieptin sensitivity. Emerging evidence has shown proinflammatory effects of Ieptin implicating it in the pathogenesis of inflammatory conditions [108], and thus lower Ieptin is consistent with an overall anti-inflammatory effect of carbohydrate restriction (discussed later in this chapter)."

Full-text references:

[56] = ... 09-170.pdf

[108] = ... tent-block
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