Atrial Natriuretic Peptide a Possible Clue to UARS, and Obesity

Guest post by Dr. Deborah Wardly.

Recently, my hypothesis paper on Atrial Natriuretic Peptide (ANP) was published, which discusses various actions of ANP and how they might relate to the clinical presentation of OSA and UARS.  ANP is known to be elevated in OSA as a result of intrathoracic pressure changes during apneas.  This has been noted to be a cause of nocturia in OSA, but there may be other previously unrecognized effects.  For example, ANP is very important in lipolysis; the breakdown of fat.  But in obesity, there is ANP resistance; meaning that even if there’s lots of ANP around, the body doesn’t see it, so the effect is as if the levels are low.  Therefore, ANP resistance might be the key to understanding the obesity in OSA (as well as obesity in general, depending on how prevalent we believe OSA to be); there is evidence that hypoxia may lead ultimately to ANP resistance, suggesting that in OSA, it is the OSA that CAUSES the obesity, and then this becomes a vicious cycle, since we know that obesity makes OSA worse.

Other effects of ANP implicate its possible role in “adrenal fatigue”, due to the fact that ANP suppresses the hypothalamic-pituitary-adrenal axis.  In the absence of hypoxia, as in UARS, this would be more prominent and ANP levels and effect should be much higher than in OSA because there would be no ANP resistance.  This would also explain why those with UARS are thin, as lipolysis would be activated by the high ANP levels.  A hallmark of adrenal insufficiency is orthostatic hypotension, something seen in UARS.  ANP would explain the blood pressure differences seen in UARS and OSA: ANP itself lowers blood pressure, explaining lower blood pressures in UARS and then with ANP resistance in conjunction with other factors, the fact that blood pressure rises in OSA.  ANP levels go up with exercise, and would explain the exercise intolerance seen in fatiguing illnesses.  This theory argues that UARS underlies potentially ALL cases of adrenal fatigue, and possibly most cases of chronic fatigue syndrome.  It also argues that the increase in somatic symptoms seen in UARS are mainly due to the actions of ANP.

A high level of ANP doubles the excretion rate of magnesium from the kidney, putting those with sleep disordered breathing at higher risk of magnesium deficiency.  Magnesium deficiency from sleep disordered breathing may implicate its involvement in the development of obesity, insulin resistance, atherosclerosis, preeclampsia, hypertension, arrhythmia, inflammation, migraine, and asthma.

There are gender differences in ANP secretion that might explain the gender differences we see between OSA and UARS.  For example, testosterone completely eliminates stretch induced release of ANP.  Therefore, according to this theory, men with sleep disordered breathing and adequate testosterone levels, would have lower levels of ANP caused by their apneas, and therefore fewer somatic symptoms, compared to women.

There are also polymorphisms of ANP that would lead to much higher levels of ANP in some individuals; might these be the people we see with severe UARS?

As patients with OSA, what has been your experience?  Did you have sleep problems only after you gained weight, or did your sleep problems precede your weight gain?  If you are a man with UARS, do you have a low testosterone level?

Please note: I reserve the right to delete comments that are offensive or off-topic.

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8 thoughts on “Atrial Natriuretic Peptide a Possible Clue to UARS, and Obesity

  1. This article is fascinating. You have synthesized so much research related to ANP (and other hormones) and UARS/OSA in a detailed but readable publication. You have uncovered what are potential mechanisms for the confusing clinical situations we see (UARS primarily in thin patients) and pointed the field to future investigations that would examine some of the unanswered questions in more detail. I look forward to reading more about this in the years ahead.

  2. Sleep problems (UARS), fatigue, and excessive daytime sleepiness preceeded weight gains. However, proceeding my Retraction Orthodontics, did I find health related problems such as hypertension, anxiety, depression, social and behavoir and cognition disorders.

  3. Very interesting. Thanks for making time to share what you know. From Wikipedia: The appellation of “Doctor” (from Latin: teacher)…

    Also, thanks SO much for lining up Dr. Bonuck! I can’t wait to register. Sleep has made a huge difference on my daughter’s behavior and your and her work helped set us on that track.

  4. well, she (Dr. Gominak) seems a little over-focused on vitamin D, and hasn’t yet made the connection between her patient’s headaches in OSA and increased intracranial pressure. I am impressed that she looked deep enough in her headache patients to find that 9 out of 10 of them had abnormal sleep studies. the sleep apnea problem in humans is much deeper than being caused by a vitamin deficiency and I think it more likely that it is OSA that contributes somehow to vitamin D deficiency. I just haven’t figured out how yet. but what is not in my paper is the fact that ANP inhibits the hydroxylase enzyme in the kidney that converts 25 hydroxyvitamin D to it’s active form. this would not account for low 25 hydroxy vitamin D levels, but might account for low 1, 25 hydroxy vitamin D levels.

  5. Interesting. But please keep in mind it’s not a vitamin deficiency. Vitamin D is not a vitamin, it’s a hormone. You’re comment about being “deeper than a vitamin deficiency” reflects the bias Dr. Gominak exposes as problematic. (I recommend viewing her video lectures on YouTube.) There’s another doctor, Lacarin, finishing up a phase 2 trial in France on sleep apnea and vitamin D, but he did it wrong–giving a single bolus of 400,000 IU 25(OH). This is a very unnatural way to for human beings to experience vitamin D. But his reasoning makes a lot of sense; low vitamin D must be involved in “reduced upper airway muscle tonus and/or unstable neuromuscular output.” If a person’s body is trying to conserve energy yet suck in oxygen during sleep, any slight disruption in physical airflow (from narrow jaw, large tonsils, etc.) or muscle function (low D) is bound to lead to symptoms of sleep apnea. They may complement each other (or is “conspire” a better word).

  6. thank you, this is fascinating. she has some very good points. she references a paper that showed that ANP is modulated by vitamin D. I have to wonder if there is some negative feedback regulation such that if the ANP level goes abnormally high, it suppresses D absorption. she still doesn’t seem to understand that all humans have OSA, that this is what is causing the sleep disorder, and maybe D deficiency just makes this worse somehow. there are lots of things that will make people feel better, despite underlying OSA. she didn’t mention if she repeated the PSG after D supplementation and clinical improvement. but again, I applaud her investigations, observations, and ability to think outside the box.