Friday, 1 August 2014

Negative feedback loops, Tolerance, Dependence & Withdrawal.

I couldn't find the plot that I was looking for, but this electrical plot is equivalent.

eA represents the amount of a substance that perturbs one of the body's negative feedback loops. The amount oscillates between 0V & 100V.

eR represents the effect of the substance on the body. 100V represents maximum effect and -100V represents maximum anti-effect.

The very first time that the substance is taken, there is 100V of effect, initially. As the time-constant of the negative feedback loop "kicks-in", the effect decays exponentially. Just before the substance is discontinued, the effect is down to 36.8V. Just after the substance is discontinued, the anti-effect is -63.2V. If the input continues to oscillate between 0V & 100V, the effect & anti-effect eventually become equal in magnitude. This is known as "cycling".

If the substance is applied continuously, the effect decays exponentially to 0V. When the substance is discontinued, the anti-effect is -100V initially, but decays exponentially to 0V.

This is analogous to drug tolerance, dependence & withdrawal, where eventually, the user has to take the drug just to feel normal, and discontinuing the drug gives the worst withdrawal symptoms ever, initially. After the drug has been discontinued for a while, the withdrawal symptoms decay exponentially to zero.

The above also applies to supplements that perturb one of the body's Hypothalamic Pituitary NFB loops e.g. the HPA (Adrenal), the HPG (Gonadal) or the HPT (Thyroid) Axes, or any other system (as everything in the body is regulated by a negative feedback loop).

This explains why a supplement can work really well at first, then its effect decays exponentially, until there is zero effect. The loop has compensated for it.

EDIT: If a loop is broken, due to zero secretion of one of the hormones controlling it, then a prescription drug/hormone restores the loop's output level to normal. E.g.

1) Prednisone for a broken HPAA (primary, secondary or tertiary hypoadrenalism) e.g. Addison's Disease.
2) Testosterone (men) or progesterone (women) for a broken HPGA (primary, secondary or tertiary hypogonadism).
3) Levothyroxine for a broken HPTA (primary, secondary or tertiary hypothyroidism) e.g. Hashimoto's thyroiditis.

I'm on 2) & 3), due to a broken pituitary gland. Luckily, it's not completely broken, so I don't need 1).


weilasmith said...

Hi, Nigel. i wrote on wooo's blog that you were only just trying to help me, that you were not trying to dominate. then she freaked out, so i deleted my nasty comebacks and have decided not to engage her on her blog. i'm here cuz i want to ask you about all this 'autie' stuff. do you really have asperger's? what about wooo is autistic? my brother has a step-son with asperger's and he has a very sweet nature. i'm just curious if all this autie talk is for real or are you guys just throwing it around to insult each other.

Nigel Kinbrum said...


I haven't been officially diagnosed by a doctor, but three people (two psychologists and one woman who works with Autistic children) told me in casual conversation that I had Aspergic traits.

I took it as a compliment. I've always been into gadgets rather than people. See and for some insight.

I don't know what Wooo's problem is, as I'm not qualified, but she's definitely got a problem, including a severe lack of self-awareness. She's very nerdy, so I suspect that she's like me i.e. a very-high-functioning autie.

I think that a lot of her "followers" encourage her behaviour, as it's entertaining for them. Just my opinion. Wooo & I used to get on. See

Anyway, that's enough about me. Let's talk about you!

Kathy said...

So are you saying adrenal and thyroid replacement supplements have a built-in fail? I tried weaning myself off adrenal replacement (Cytozyme AD) but was miserable without it -- aren't they necessary for treatment and healing?

Nigel Kinbrum said...

Sorry to keep you waiting - I was having a mid-afternoon nap!

The effect of a supplement depends on whether the loop is working normally, or whether it's broken.

I have a dysfunctional pituitary gland, so my HPTA & HPGA are broken, due to zero secretion of TSH & LH. I take thyroxine & Testogel to raise my FT4 (also FT3) and Free Testosterone levels into the Reference Range.

Bodybuilders sometimes take T3 as a "fat-burner". The problem with that is that it perturbs the HPTA, so TSH is suppressed. If enough T3 is taken, TSH becomes completely suppressed and the closed loop becomes an open loop, where more T3 raises metabolic rate.

When the T3 is eventually discontinued, the zero TSH level means that there is a temporary crash in thyroid hormone levels until TSH secretion restarts.

The same sort of effects occur with Prednisone. It's fine if the loop is broken due to zero secretion of ACTH, but if it's used on a working HPAA, it'll suppress ACTH secretion.

Hope that helps.