What causes and influences PCOS?

What causes PCOS?


Many of the PCOS “experts” out there do not understand the connection between the endocrine system and the reproductive system.  Because of this, they miss a very important link between metabolic syndrome and PCOS.  I have read maybe a dozen books about PCOS that recommend nothing but taking birth control pills in response.  This puts a patch on a problem that is, in the authors’ views, a simple result of genetics. Some idiots go so far as to recommend a low fat, low carbohydrate, moderate protein diet.  WTF is left?

Others—the real doctors, not the one’s publishing books—understand that PCOS is a disorder of the endocrine system.  It is not just an ovarian problem, but is rather a problem of hormone signaling to and within the ovaries.  This means that ovarian hormone production, pituitary action, and even hypothalamic action are all crucial for proper reproductive health.  Check out the Journal of Endocrinology’s 681 articles on PCOS if you want to know more about that.


What makes PCOS so hard for doctors to figure out is not just 1) the grab bag of symptoms but also 2) the heterogeneity of its population.  There are two primary groups of PCOS patients.  In the first group are about 60 percent of the patients, all of whom are overweight.  More importantly, they are insulin resistant.  High levels of insulin in these patients shift hormonal balances away from estrogen and towards testosterone.  Insulin directly stimulates testosterone production.  It’s pretty clear to endocrinologists how to fix this problem.  Lose weight, and create better insulin sensitivity.  Low carb (specifically low fructose!) diets, exercise, and intermittent fasting are all excellent means by which to do this.  The issue is much more complicated than this–really, it is, and many overweight women still have some issues when they lose weight–but it can more or less be boiled down to these steps.  On the other hand, the problem is a fair bit more complicated for the other 40 percent, the “thin cysters.”   If it’s not overt insulin resistance causing their issue, what is it?

It’s a lot.  I’m a thin cyster, and, by gods, have I tried everything to shake this damn condition or what.  For the last couple of years I have spent the majority of my free time researching PCOS.  This was mostly because I wanted to get rid of my acne, but infertility, insulin resistance, diabetes, heart disease, and ovarian and endometrial cancer aren’t risks to laugh at, either.  Up to this point I have learned a shit ton about the endocrine system (but certainly not everything and I am NO expert), and I want to share with you as much as I can.

Things that give people PCOS and why

 Overweight, metabolic derangement and/or insulin resistance

        Like I just mentioned, metabolic derangement is the single greatest cause of reproductive derangement in women.  Insulin makes ovaries produce testosterone.  This is bad news.  We all need testosterone—it’s the crucial hormone for generating sensation in the clitoris!—but too much can entirely derail that.


Dramatic weight loss

        Fat cells are major players in endocrine systems.  This means that any kind of weight fluctuation can significantly disrupt endocrine function.  Primarily, this is an estrogen problem.   Estrogen is produced in fat cells.  When people gain weight, their estrogen levels increase (obese PCOS patients might have elevated testosterone AND estrogen).  When they lose weight, they decrease.  I have discussed androgenicity a lot so far, and it is the most universal element in diagnosing PCOS, but estrogen levels are crucial for proper reproductive signalling with the pituitary gland.  Moreover, higher levels of estrogen can “block” harmful effects of androgens, such as acne.  For these reasons,  it may be more important to have proper balance between testosterone and estrogen rather than having good absolute value of both hormones.  For example, when I was first tested for PCOS, my testosterone was slightly elevated and my estrogen was slightly depressed.  These weren’t alarming numbers in either case, but combined they spelled serious issues.

The jury is still out on the long term impact of weight loss.  Can someone lose weight slowly and maintain reproductive health?  Does the speed with which she loses weight matter?  If someone loses a significant amount of weight, will her ovaries ever “learn” to make up for the estrogenic load her fat cells used to give her?

From what I can tell from my own experience and talking with others, the answer to each of those questions is “sort of.”  I used to be at a BMI of 25 (5’2, 130 pounds).  In three months I dropped to approximately 18 (105 pounds) and today sit around a BMI of 20, perhaps, 113ish pounds.  I prefer not to know.  In any case, I am not malnourished and I certainly look healthy—much more so than I did before when I was supermodel thin–but this has not increased my estrogen levels at all.  In fact, they have continued to drop.  This is probably due to some other factors, which I’ll get to later, but putting on weight hasn’t been the answer.   If it were, I would have seen a bit of normalization with my increase from 105 to 115 pounds.   In this time period, my estrogen has dropped but my testosterone dropped, too, which is good, and LH and FSH remained normal.  Moreover, I have been experiencing irregular periods and symptoms of low estrogen such as insomnia and hot flashes since I was a young girl, and I have also been amenhorreic at 137 pounds.  Clearly my issue goes deeper than simple weight loss and weight gain.    Weight fluctuations trigger the surfacing of some my problems, but it is not what planted them there.


Excessive exercise or super low body fat– or maybe even just weight loss in sensitive individuals

        This issue is virtually the same as the one above, except the literature on it is more extensive, and it relies less on the actual production of estrogen in fat cells and more on being in starvation mode.  When you burn calories at a high rate, and when you consume a low calorie diet (and also if you’re consuming too much fructose!) your leptin response is restricted.  This means that less satiety is reaching your hypothalamus.  The hypothalamus is in charge of telling the rest of the body how nourished it is, and whether or not it should be running on “conserve” mode and shutting down peripheral systems such as reproduction.  To do this, it releases Gonadotropin Releasing Hormone, which signals to the Pituitary to release FS and LSH, the hormones that tell the ovaries to produce sex hormones.  Without leptin, GRH is impeded, and the entire neuronal cascade is impeded.  No proper balance of pituitary hormones is produced.

It is absolutely crucial to convince the body that it is not starving in order to mitigate PCOS.  The problem comes with how exactly to do that.  There’s no formula.  Exercise less, eat more.  Eat different foods.  Not fruit.  Seems as though other carbohydrates — glucose — have the highest of all leptin responses.  I’m not sure, and I’ve spent a hell of a lot of time trying to figure it out.  It has been my experience that a higher carbohydrate diet, even though it makes me want to eat more and puff up a little bit, increases my sex drive and vaginal lubrication (both indicators of estrogen production).  As I mention below in the diet section, this result cannot be truly trusted, however, since legumes (containing phytoestrogens) were included in my high carbohydrate diet experiments.



        Sex hormones are produced in our bodies via two axes: the first is the specifically reproductive axis which includes the pituitary gland and the ovaries, and the second is the adrenal system.  If a body has fatigued adrenals in any significant fashion, it’s hormone cascade can be seriously disrupted.  Cushing’s disease, an adrenal disorder that causes abnormal cortisol production, often causes PCOS in its patients.

Literature seems to show, however, interestingly, that cortisol hinders testosterone function.    When women present to evolutionary medicine folks (and regular medicine folks) with symptoms of estrogen dominance, such as PMS or abdominal fat, they are advised to reduce stress.  So then: should you stress yourself out because you want your testosterone to decrease?  No, Crazies.  What is ideal is hormonal balance, and the endocrine system is so complicated and our understanding of it so limited that reducing stress should be the number one on everyone’s health agenda, period.


Metabolic derangement during puberty

        Check out the book Ancient Bodies, Modern Lives by Wenda Trevathan for an excellent book on fertility in general.  It’s where I first read this theory, that whatever physiological state a girl is in in when she begins menstruating can affect her cycle for the rest of her life.  Trevathan proposes that conditions of famine and bounty are determined by this metabolic state, such that deviating from the start-of-puberty norm triggers famine or bounty responses in a woman’s body.  For example, many rail thin women in the world, particularly in developing countries, menstruate their entire lives.  But when someone who has a BMI of 25 loses 15 pounds, or maybe has less of certain micronutrients in her system, and also has some metabolic derangement from other sources, her hypothalamus might think this is a period of starvation and turn off her reproductive response.

A lot of evidence in the pathogenesis of PCOS, specifically in thin women, points to problems during puberty, childhood, and even the womb (if someone’s mother’s hormones are messed up, hers will be, too.)  Menstruation is kicking into gear earlier and earlier in young girls.  The middle teen (~14-16 years old) menarche that used to be the norm is now considered “late,” and the average age of menarche in American girls is 11 years old.  Evolutionarily, this is quite young.  This is partly because young girls are heavier than they used to be.  Menstruation starts when a certain estrogen level is reached in the body, and estrogen is not just produced in the ovaries but also in fat cells.  The problem therefore is that the ovaries sometimes start out with a handicap, as I touched on above.  They are dependent on the fat cells.  So any time weight fluctuates, ovaries necessarily have to adjust, and often do so poorly.

Another factor is related: childhood insulin resistance.  Having high testosterone levels at a young age primes the body to always act in that fashion.  This spells trouble for the entire endocrine system.  Please feed your children real food.



        I explored the link between hypothyroid and PCOS for a while last year, and I wrote about it here.  I abandoned my quest when I didn’t see much improvement and may have overdosed on iodine, unknowingly taking upwards of 2000 percent of the daily allowance for a significant amount of time, but I have remained aware of how important the thyroid hormone is for reproductive function.  If you want to really learn about thyroid functioning, visit www.chriskresser.com.  His work is brilliant and thorough.

Thyroid hormone is made in the thyroid gland.  First, however, thyroid stimulating hormone, TSH, is produced by the pituitary (after being signaled by the hypothalamus) and sent to the thyroid gland.  This instructs it to make T4.  T4, though it accounts for 99 percent of the thyroid hormone in the bloodstream, is inactive, and rather just floats around in until the body needs more of it.  T4 is converted to T3, which is then used by every cell in the body.  In this way, T3 is the hormone of primary interest.  Things can go wrong at any step in this process.  TSH can be underproduced, and either or both of thyroid hormones can go missing.  T4 can be underconverted to T3.  Someone can be dealing with an inflamed system, menopause, or Hashimoto’s thyroiditis (accounting for approximately 90 percent of hypothyroid cases), and in each case the functioning of every cell in the entire body is impaired.  T3 is as crucial for cellular function perhaps as ATP, so you had best have your thyroid health in mind no matter what your presenting condition.  This can be bolstered by proper iodine intake, high dose iodine in the form of iodoral, or supplementation with T3 or T4.  Whichever step one takes depends on where her endocrinologist sees the problem occurring.

Because every cell is dependent on T3, and because bodies try to optimize its T3 resources, peripheral systems such as reproduction can be shut down in favor of protecting other systems.  If the thyroid is malfunctioning, the hypothalamus may reduce signalling to the pituitary gland in order to protect the thyroid system as much as possible.  This is analogous to the phenomena of starvation.   Another possible point at which hypothyroidism influences PCOS is at the level of cellular functioning.  If there isn’t enough thyroid hormone in a cell, it will shut down or become sluggish independently.  Reproductive tissues, such as those in the ovaries, might therefore not have enough energy or resources to produce estrogen at the proper rates.

PCOS patients who present with subclinical levels of thyroid hormone begin ovulating once regular thyroid functioning is achieved.  One of my favorite articles (because it gives me hope) reports that thyroid hormone replacement therapy achieves a “significant reduction in total as well as free testosterone,” and also states that “ovarian volumes of patients with hypothyroidism were significantly great compared with controls, and their magnitudes diminished significantly during thyroid hormone replacement therapy.”

BPA, environmental toxins, and endocrine disruptors

        I mentioned before that thin women with PCOS present with greater gland and endocrine dysfunction than overweight women.    What is the root of this malfunction?

One plausible answer is environmental toxins. The primary ones about which we should be concerned are pesticides and BPA.  Almost all fruits and vegetables are covered in chemicals that act as phytoestrogens in the body, and over time, specifically when young, these can have a major impact on reproductive physiology.  Some foods are worse than others.   This information is easily accessed via google.  The way to mitigate this is to eat organic, to peel your vegetables, or to wash them.  A great way to wash them to make sure the endocrine disruptors get mitigated is by soaking them in vinegar for several minutes.  Vinegar binds with some of these toxins and will help chelate them off of the skin of your vegetables.

A second endocrine disruptor, perhaps the most prevalent one in American lives today, is BPA.  BPA is a polymer leached from plastics that disrupts endocrine function in a way not entirely yet understood, but appears to have “estrogenic” effects.

When rats are exposed to BPA, their male offspring have decreased fertility, and only after exposure to small doses.  Of the male rats, one study concludes:

“The BPA exposed males had a suite of reproductive deficiencies that collectively created subfertility in the rats. Some of these included lower sperm counts, poor sperm motility and cellular defects within the testes. Circulating levels of testosterone, estrogen and other reproductive hormones were also significantly lower.

The BPA exposed males were also significantly heavier than unexposed controls.

Mating behavior was also negatively impacted. The BPA-exposed males took longer to copulate with females and a few failed to copulate at all. These observations suggest that the males had lower sexual motivation.

Potentially most concerning, is that the sons and grandsons of the exposed males were also subfertile, indicating that the germ line itself was damaged by the initial exposure to BPA. The mechanism for this transgenerational effect is unclear.”

Female rats are affected just as strongly, if not worse.  THEY GET PCOS.    Not only do they present with cystic ovaries, but they have increased testosterone and estrogen levels, and also decreased progesterone.  Recall that progesterone is THE crucial hormone for menstruation.   They also have lowered fertility and higher BMIs than non-exposed rats.

If that doesn’t convince you BPA is bad, note that this result has also been reported in human females.  A high correlation has also been shown between mothers with high levels of BPA having children with mood, behavior, and personality disorders.

Moreover, women with PCOS, both lean and overweight women, have 40 percent higher levels of BPA in their blood than those without.  However, the levels are even more markedly increased in thin women with PCOS.  In thin women, PCOS patients had 1.6 times ordinary BPA levels, and in overweight women the ratio was just 1.3.  Some researchers speculate that this is because BPA is being stored in fat cells, while other posit that BPA causes brain-related hormone signaling dysfunction, which could explain why thin people end up having PCOS at all.  The question of causation rather than just correlation remains, however: does BPA cause increased testosterone levels or do increased testosterone levels inhibits the body’s ability to clear BPA out of its system?  Erring on the side of caution, I decided to eliminate all of my consumption of BPA-touching foods, and specifically to stop drinking (and microwaving!) ALL OF MY WATER out of a plastic mug.  Idiocy, I know.  The result?  One week later the bumpy acne on my forehead disappeared, after having been persistent for years.  While other factors are always at play, I didn’t change anything else.  It was as controlled an experiment as I was going to get.

All that said,

Hard plastics, the polycarbonate plastics such as #7, are worse than soft plastics.  Plastics 1, 2, and 4 seem to be BPA free.  Heated plastics leach at much higher rates than cold ones (such that buying frozen vegetables is not as scary as one might originally imagine.)   However, just because a plastic is free of BPA does NOT mean it is free of estrogenic activity.  All plastics have EA–Estrogenic Activity–just from different chemicals and in different amounts, with not any of them yet measured significantly.  Finally, research has shown that BPA gets into bodies in even higher doses from eating out of aluminum cans than out of plastic.  Cans are lined with BPA on the inside, so viritually everything you eat out of a can is swimming in BPA.   Here’s a  list of consumer tips if you’re interested:  http://www.ewg.org/bisphenol-a-info.

Another source of environmental estrogens is body applications.  Parabens are phytoestrogens and are one of the most common elements in lotions and soaps.  Consume organic here, or check labels, or, even better, stop washing altogether.  I promise I don’t smell.  Also importantly, there’s a fuckton of BPA in receipts. I know!  So if you’re a cashier, seriously, you can ask your boss to let you wear gloves and she had best say okay.


Liver dysfunction

        Glands get hormones pupming into the bloodstream, but the liver filters them.  I’ll talk more about what one can do with a liver below.


Pituitary or hippocampal tumors

        This speaks for itself.  If your LH, FSH, TSH, or Gonadotropin Releasing Hormone levels are significantly impaired, tell your doctor you want an fMRI.



1)        Limit insulin responses, especially if you are overweight or insulin resistant.  Lowering insulin decreases testosterone production.  How to do this is really complicated, though fasting and low carbohydrate diets seem to do the trick.  Be careful, however:  Notably for paleo and low carb dieters: low carbohydrate diets can reduce the conversion of T4 to T3 in the liver, inducing hypothyroidism.  Look out for this if you’ve been low carb for a significant period of time, if you have a low body temperature, and/or if you are a thin PCOS patient.

2)        DON’T EAT SOY.   Soy is a phytoestrogen.  Phytoestrogens resemble– but are NOT THE SAME as– estrogen in the body.  This leads to confusion in the endocrine system (and, significantly, breast cancer.)   Remarkably, soy may play a greater role in endocrine disruption than BPA.  Phytoestrogens can help mitigate some side effects of low estrogen levels such as hot flashes, but they cannot perform the proper signaling functions of true estrogen.  This means that exposure to BPA results in a body totally devoid of proper estrogen.  When the body detects “estrogen” in its bloodstream, it stops producing it on its own.  In this way, phytoestrogen consumption decrease estrogen levels at the time of ingestion.  Perhaps more importantly, however, it might also impair the body’s ability to produce estrogen, since the ovaries essentially get out of practice.  This is similar to the issue of gaining or losing weight.  Soy, like excess weight, is a “crutch” for the ovaries.  But it goes beyond that simple role in that it is a malfunctioning crutch, only working in certain circumstances.

One study done measured phytoestrogen levels of different foods, and while some vegetables had an order of magnitude greater than others, soy itself has 10,000 units per gram, rather than 4 or 5 hundred like other potent vegetables.  (I just spent a half hour looking– I know it’s on ScienceDirect– I’m sorry!)  Soy is the number one food you want to avoid if you have PCOS.

3)        Legumes, nuts, and seeds also act as phytoestrogens.

4)        Don’t eat dairy.   Pregnant cows produce a protein that inhibits testosterone blocking within our own systems, such that dairy is the most androgenic food out there.  Don’t eat dairy if you have PCOS or if you are worried about your androgen levels at all, especially if you want to decrease your acne.  I mean it.  Dairy also has a significant insulin response, which can irritate acne and PCOS.


Other foods have less dramatic impacts but may be important to consider for hypersensitive PCOS patients.  My hormone levels probably wouldn’t be all that different if I ate a more varied diet, but because I am so careful to avoid androgenic and phytoestrogenic foods, I have managed to get my acne under pretty good control while I begin playing with clinical methods of treating my PCOS.   I seem to be quite sensitive, so it’s definitely worth a shot if you think you are.


5)        Factory farmed meat is injected with Bovine Growth Hormone, which can increase insulin-like growth factor 1 in humans.  This is bad.  Other hormones such as estrogen and testosterone are approved by the FDA for injection into the animals via an earpiece each animal is implanted with at birth.  The FDA claims that even with supplementation the animal’s hormonal profile falls within normal ranges, but I’m skeptical.   Aside from noticing that my acne gets worse whenever I eat meat, chicken, or any other farmed animal (not fish), I also noticed that while in Taiwan I rarely got new cysts, except for one day I ate hamburger meat from Costco.  I don’t know if they put anything nefarious in the meat, but I had volcanoes all over my face the next morning.  It’s also possible that natural levels of hormones in all meat affect me just as much as the factory-farmed sort.  I haven’t done any experiments to check.

6)        Cruciferous vegetables.  These veggies not only act as goitrogens and can decrease thyroid functioning when eaten raw, but they also promote the activity of cytochrome P450 enzyme CYP1A2.  This enzyme resides mostly in the liver and is responsible for clearing estrogen out of the system.  People often say that “excessive consumption” of cruciferous vegetables should be avoided, but that didn’t stop me from eating a pound or two raw per day.  It was hard not too, considering how limited my own diet is  (I eat primarily vegetables and fish, and wild game when I can get my hands on it).  In any case, my estrogen levels have continued to plummet over the last year, despite putting on a bit of weight, and I think this might have something to do with it.

The one food that has been found to reverse this “on” effect on cytochrome P450 enzyme CYP1A2 of cruciferous vegetables in the liver is grapefruit.  This is well documented in the medical literature.  Grapefruit is the only food that promotes estrogenic activity without acting as a phytoestrogen, so far as I can tell.   Be careful since this enzyme also inhibits the processing of a wide variety of drugs, but if you’re low on estrogen, don’t eat soy, eat grapefruit.

7)  Experiment with low carbohydrate (fructose!) and high carbohydrate diets.   Carbohydrate elicits a greater leptin response than fat.  Leptin is the hormone responsible for signalling to the hypothalamus that the body is sufficiently fed.  Without leptin, the body feels very hungry and might think it is living in a time of starvation.  This is one of the primary causes of amenorrhea and PCOS, presumably, as I described above.  That said, if you are a thin PCOS patient and are not insulin resistant, you might want to try eating a high carbohydrate (Safe starch!  Potato, taro, sweet potato, yam, white rice!) diet.  If you are an overweight PCOS patient, you probably want to eat a lower carbohydrate (again, most importantly, fructose) diet to limit insulin in your body as much as possible.

This past fall I experimented with higher carbohydrate diets.  I experienced greater vaginal discharge and sex drive when I ate a higher carbohydrate diet.  However, there were legumes involved in this diet, so there are too many variables to draw proper conclusions.  I remember one night in particular in which I ate a lot of potatoes, and I felt great,  wanting-to-skip-down-the-hall-to-my-room-every-thirty-minutes aroused, hah, for the rest of the next day.  But that’s all I’ve got so far as anecdotes go.

8) Experiment with fasting.  Fasting decreases leptin levels.  If you are overweight, intermittent fasting can really help you increase your insulin sensitivity and lose weight.  It can help you decrease testosterone.  Yet if you are thin, fasting might further convince your body that you are starving.  I really love to fast, but I have begun experimenting with addressing my hunger immediately.  Unfortunately I have nothing concrete to report on this point: it’s too soon to tell.


What can somebody with PCOS eat?  Whatever they want, I suppose.  EXCEPT FOR SOY AND DAIRY AND SUGAR, holy crap it’s just not worth it.  In any case, it entirely depends on the patient, how much of a perfectionist she is, and how she reacts to certain foods.  It depends on her medication, her doctor, and her choices.  Experimentation is key. It’s taken me ages to figure out what I can eat to minimize my acne and to maximize the function of my ovaries.  With the drugs I’ve started taking, I imagine I’ll be able to start integrating in other foods such as cruciferous veggies, meat, and maybe even a bit of dairy in a few months.  This is a part of why PCOS treatment is important.  It enables you to eat a diet rich in all of the nutrients.  In the next post I’ll expound a bit more on food and on the different treatment options for PCOS.

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01 2012

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  1. Whitney #

    Thank you so much posting this! I have PCOS but all my doctors, family and freinds don’t take meor my symptoms seriouly becuse I am under weight. I really hope I can heal myself.

    • 2

      There are some excellent doctors in the Philadelphia area that could be of help if you are near there.

      Also – it is my understanding that the adrenal release of testosterone plays a big part in thin women with PCOS. You might want to try things that support the adrenals like licorice extract and adrenal cortex extract (try this second). Also, skullcap can decrease ACTH output and along with licorice can decrease the stimulation on the adrenals. I am trying this on a few patients and will let you know. Also try to keep stress low if possible – cut out coffee, don’t overexercise, exercise on an empty stomach (except at most 30-45 minutes at a low intensity), don’t skip meals, and get enough sleep. If insomnia is a problem, try Jarrow Stress Tame.

  2. Amy Todd #

    Thanks! I have had PCOS symptoms recently, on and off and I am curious about it. I have been Paleo for about a year and experience it probably more now than before, so that makes me a little frustrated. I have removed so many other bothersome symptoms on Paleo, but now this is most noticable. At least I notice it more now since I have lost weight and I am more in tune with my body. As of right now, I can feel a little twinge down there and I am late with my cycle and no I am not pregnant!! Thanks so much for doing the research, I too have researched so much for my health, but I haven’t researched PCOS as much, seems a bit daunting, so thanks so much for sharing! I am definitely staying tuned.

  3. Gabe A. #

    You come to some interesting conclusions. It does sound like your hormonal history has been a roller coaster ride, a shame. It is hard to sort out the endocrine system and HPA axis, so keep digging. For one, thyroid status is paramount and the most difficult due to the lack of effective pharmaceuticals. T4 often does not do the trick and can worsen symptoms. T3 needs to be given in proper proportion to T4, but is not available in an extended release form. One may have to take bits of one tablet throughout the day to achieve a desired effect. Also, desiccated glandular thyroid used to be the best but is now formulated differently which may require crushing for proper absorption. Supplementing iodine can be good but must be accompanied by selenium as well to prevent toxicity.
    I think estrogen is the main culprit and by this I mean unopposed estrogen. You hit the nail on the head when you mention progesterone (the real “female” hormone). I’m not talking about progestins which are synthetic and have been linked along with estrogen to some really awful conditions. Proper thyroid hormone function is required to utilize cholesterol for pregnenolone production in the mitochondria (mitochondrial health is VERY important). The cells may then produce progesterone and other steroid hormones from this. The problem is estrogen opposes thyroid function in a complicated way as it is tied to increased cortisol (sensitive to unstable blood sugar, stress, infectious burden, etc.) The problem with this is that high cortisol causes the release of free fatty acids which suppresses thyroid and impairs insulin sensitivity and begets higher insulin levels which beget increased estrogen production and the vicious cycle continues. These free fatty-acids tend to be polyunsaturated which can be poisonous to the thyroid, mitochondria, and increase AGEs. All this leads to hormonal imbalances. The “high carb” diet helped you in this respect due to its mitigation of the stress response pathway and increased the turnover of cholesterol to beneficial sex hormones (pregnenolone, progesterone, testosterone, DHEA). This is not too detailed but the best I can do for now.
    Leptin is a strange character. Many think of it as a satiety “hormone” but recent evidence is grouping into the cytokine family related to IL-6. IMO it has a more pronounced effect with glucose based “carbs” because it functions partially to protect the body from glucose/lipotoxicity. An unnerving issue is its effects on the aromatase enzyme, as it has been shown to increase it’s activity thus increasing peripheral estrogen production. Many associations get muddled due to the multifunctional aspects of physiologic “messengers”.
    Lastly I will say this. I don’t believe insulin is THE problem so much as it is the chronically heightened level due to the stress response and chronically high cortisol levels. Remember, proteins such as leucine have a profound insulin secreting effect. This gets lost as the focus of insulin revolves around glucose as if it was it’s only role. This is why I don’t condemn dairy as it has beneficial protein and sugar to stimulate insulin so that energy is delivered to the cells (bodybuilders often use it to extreme effect). Also, the high calcium from dairy helps to balance the phosphates in the diet which suppresses the parathyroid response. Enough said, sorry so long. I would love to share ideas in the future if you would be interested.

    • pepper #

      I like your comment about the complexity of the insulin issue. You’re right, we do well by minimizing it, and clearly epidemiologically this method works for a lot of people, but it’s not as simple as I have portrayed it.

      What do you think are the most important foods, actions, meds etc for mitochondrial health?

      • Scott Roland #

        Mitochondrial health will be supported by any compound that helps reduce organic matter into energy, and of course, there are several internal mechanisms and exogenous nutrients that aid in this process. Metformin should help in this regard, but it doesn’t always have a harmonious relationship with the liver—only at higher doses, though. But for the sake of reducing cognitive strain, I think mitochondrial health can be simplified to the mechanical activation of adenosine receptors—or reducing the heart rate, and increasing the utilization of phosolipids—which can be accomplished by using compounds that have an affinity for members of the protein kinase C signaling cascade. However, it’s easier if you just think in terms of inhibition, and activation. For instance, since dopamine affects utilization of sodium, then sodium should influence the utilization of dopamine. Or since the utilization of gamma amino butyric acid is affected by magnesium, then gamma amino butyric acid should influence the utilization of magnesium. So what it really comes down to is relaxing, maintaining a good sleep architecture, and trying to moderate your body’s arousal.

    • Scott Roland #

      For the synthesis of thyroxine, iodine is indeed critical, but tyrosine is needed as a cofactor. But to be reduced to the more biologically active triiodothryonine, selenium is needed for this reaction. As you suggested, one has to be very careful with dosing, because too much selenium will alter the rate of synthesis of thyroxine, and vice versa with thyroxines cofactors.

      Anyway, physiology, like nature is deeply resistant to attempts to generalize systemic processes through monocausality. So I think it would be prudent to worry less about the hormonal culprit, and rather, focus more on the correlates of messengers and mechanisms. I think we can agree that main problem is the proliferation of ovarian cysts, and to arrest this process, there needs to be a focus on reducing the rate of transcription. Since thyroid hormones should influence the kinases that take part in this process, I don’t think it would be advisable to try to upregulate its synthetic mechanisms. Rather, I think the a reduction of the following variables—all of which are interconnected—should restore homeostasis, and thus, sensitivity: glucose, oxidative stress, blood pressure, catecholamines, glutamate, dopamine, sodium, and estrogen.

      As for leptin, I wouldn’t group it with the IL-6 family of cytokines—whose expression is strongly influenced by adipose tissue, but rather, as complementary to hunger regulating hormones like ghrelin. Additionally, I agree that dairy is a good source of protein, but based on its relative amino acid content, I don’t think its necessarily the most exceptional source. In my opinion, eggs would be more deserving of this rank—and especially if the criterion is BCAAs per 100g. And to counter the effects of phosphorus—which is critical for cellular energy, it would be much safer to rely on Vitamin K dense foods, since calcium ions can’t bind to bone structures without Vitamin K.

  4. Gabe A. #

    Well, you probably won’t like this but I feel sugar is important from fruits (tropical/citrus/low pesticide) and one may supplement with it if fruit is temporarily unavailable. Sugar along with protein and salt are very good at suppressing the stress response and one needs them in amounts based on their individual stress levels. Foods that come to mind are eggs, dairy (milk & cottage cheese), beef/lamb/goat, gelatin for broths and as potein supplement, seafood from leaner wild fish, shrimp, scallops, squid, crab, oysters, etc. For sugars, pineapple, melons, citrus (fresh squeezed pulp free OJ), some in milk, potato (also a protein source!), and some white rice. All the above prepared in different combos and if cooked use a tablespoon of half butter/coconut oil or either on their own. Don’t forget SALT from pickling salt or unrefined sea salt (2-3 teaspoons/day). The salts will help body get rid of bromide as well as the iodide supplement. Lastly, targeted micronutrient supplementation is very important to balance all minerals like iron, copper, zinc, magnesium, calcium, selenium, manganese, boron, choline, etc.

    • pepper #

      No, that’s totally interesting. Why is sugar good for the stress response? I have heard often that it helps the liver by preventing it working too hard in gluconeogenesis, but maybe there are other aspects of which I am unaware? And why is fruit better than other sources such as glucose?

      • Scott Roland #

        All sacharides should help to modulate the effects of stress, but their negative effects are related to the complexity of their structure—so glucose should be the most deleterious.

  5. Gabe A. #

    The way I understand it is the liver functions best when replete with glycogen. Sugars from fruits and sucrose have been shown to be more effective in doing this. I used “sugar” as a general term regarding stress, but glucose would have been fine too. The other potential issue is that sugars from fruits and milk are absorbed higher up in the small intestine leaving less for gut bacteria further down in the intestinal tract. For some, resistan starch from undercooked potato or from other starches may aggravate the gut microbiome. Some interesting topics to research are LPS (bacterial endotoxin), leptin’s pro-inflammatory role, and tryptophan conversion to serotonin (a stressor), all interesting things.

    • pepper #

      Ah, right. I thought that might be your idea. The thing is– we really don’t need all that much for liver glycogen. And fructose is SO potent at restoring the glycogen we’d hardly need to each much of it at all. I eat far more vegetables than I need, probably far more than is healthy, honestly.

      I like your point about upper and lower intestines. Chris Kresser claims he’s never known anyone with a skin condition who doesn’t also have a gut problem. I don’t really think I have a gut problem, though I know I faced some issues many years ago.

      Serotonin a stressor?

      • Scott Roland #

        Intermittent fasting, and increasing glycolysis—through various compounds—is probably the most practical way of restoring glycogen.

  6. Gabe A. #

    I think the issue of liver glycogen storage isn’t as easy as one might think. Also, fructose is not all you’re ingesting when eating fruit or sucrose. Lastly, sucrose and corn syrup/HFCS are two entirely different animals. HFCS, for instance, was found to have 4X the calories as sucrose when subjected to hydrolysis, probably due to oligosaccharides forming in production. That would mean much of that is reaching the colon and causing GI issues. One has to remember that liver glycogen is not all sugars are used for and that the body needs upwards of 600-800 calories per day of sugars to meet its minimal glucose requirements.

    • pepper #

      That’s fascinating! Forgive my ignorance, but why would the formation of oligosaccharides increase calories? How would hydrolysis create such an energy leap? It’s been a while since my orgo so I’m struggling. My biggest problem with understanding, though, is the HFCS comparison with sucrose. Fructose to glucose seems much simpler. HFCS is 55 percent fructose, and sucrose is 50 percent fructose. That’s a fair difference.

  7. Gabe A. #

    Carbohydrate Analysis of High Fructose Corn Syrup (HFCS) Containing Commercial Beverages
    Paulin Nadi Wahjudi1, Emmelyn Hsieh1, Mary E Patterson2, Catherine S Mao2 and WN Paul Lee1,2
    1 Los Angeles Biomedical Research Institute, Torrance, CA
    2 Pediatric, Harbor-UCLA Medical Center, Torrance, CA


    The carbohydrate analysis of HFCS is based on methods which first hydrolyze the syrup into simple sugars before quantitative analysis. We have examined whether HFCS can be hydrolyzed under the same conditions suitable for hydrolyzing sucrose. A new GC/MS method for the quantitation of fructose and glucose as their methoxyamine derivatives and 13C labeled recovery standards was used to determine the carbohydrate content of HFCS in 10 commercial beverages. Samples were analyzed before and after acid hydrolysis. The carbohydrate contents in commercial beverages determined without acid hydrolysis were in agreement with the carbohydrate contents provided on the food labels. However, the carbohydrate contents of beverages determined after acid hydrolysis were substantially (4–5 fold) higher than the listed values of carbohydrates. As fructose and glucose in HFCS may exist as monosaccharides, disaccharides and/or oligosaccharides, analysis of the carbohydrate content of HFCS containing samples may yield widely different results depending on the degree of hydrolysis of the oligosaccharides. With inclusion of mild acid hydrolysis, all samples showed significantly higher fructose and glucose content than the listed values of carbohydrates on the nutrition labels. The underestimation of carbohydrate content in beverages may be a contributing factor in the development of obesity in children.

    • pepper #

      Oh I see– so the extra calories were “hiding” in the initial analysis, and revealed in hydrolysis. Thanks!

      • pepper #

        But also I don’t think they are asserting that fructose is 4-5x more caloric than sucrose, as was your implication (?). It says here that the beverages as HFCS are 4-5x more caloric than “the listed values of carbohydrates,” which I take to mean the calories listed on the nutrition label, which is also HFCS. I read the abstract as pointing out the nutrition label is wrong on caloric content, not comparing fructose to sucrose.

        • Scott Roland #

          The saccharides produced by the hydrolysis of HFCS shouldn’t have a direct impact on the most proximate mechanisms to weight regulation, but because of the relative quantity of metabolites, they can have a greater impact on receptors that play a role in hunger—like the NMDA receptors. But really, the reaction has been quite hysterical, and in many ways analogous to the aspartame controversey,

    • Scott Roland #

      I would be circumspect about the credibility of the sources that you cite.

  8. Scott Roland #

    There’s a great deal of potential with fermented foods, which among other properties, has the virtues of strengthening innate immunity, restoring an equilibrium to excitatory/inhibitory mechanisms, and up regulating acetylcholine transferase—whose dysfunction is a critical correlate in the pathogenesis in neurodegenerative disorders. Subjectively speaking, the most effective foods would be sauerkraut, kefir, and dark chocolate—which is quite palatable when combined together. Additionally, it would be wise to supplement with prebiotics like inulin—which can be procured at all drug stores.

    Although I probably shouldn’t need to remind you, you’re quite an impressive individual, and I would be quite dismayed if you found yourself subject to your physiology. So putting my cantankerous comments aside, I think it’s imperative that you conquer your own nature, and make a contribution that’s worthy of your evident talent.

  9. Gabe A. #

    You mean my source, lol. I often wonder how much of the evidence condemning sugar is confounded by corn syrup, HFCS, etc. I also feel that sugar in fruit is only one aspect of their dynamism in the diet. Many fruits are also high in salycilates and inositol, which may be beneficial nutients in the context of inflammation and insulin resistance. Lastly, if the above analysis is reproducible then it would mean that HFCS containing foods would contain many more calories from “sugar” than previously thought.

  10. Gabe A. #

    I wish I knew more about neurodegeneration. As far as fermented foods, chocolate? Also, considering lactate, might it be possible that it has a protective effect against energy excess? If I recall correctly lactate requires the consumption of glucose to further it’s metabolism. This would act as a moderate ‘stressor’ and force the liver to expend slightly more energy in return for less, would it not? Anyways, good stuff and thanks?

  11. Zingzap #

    When my symptoms started I was rail thin. As a child I was super skinny. So skinny that every time I got sick family worried even more because I had so little body fat and got even skinnier when I got sick. I hit menarche at 10 and everything went haywire. I had all the symptoms of what is now recognized at PCOS but no one told me anything. I was treated with estrogen birth control and when things got worse, recommended to consume massive amounts of soy and given antidepressants. I went vegetarian and even vegan trying to turn my health around and it just got worse. I went from being very thin to a bit chunky (I was the only one who gained weight in basic training for the AF in my flight). The chemical sensitivities got worse. After I had my kiddo it went even further downhill. Just this very negative spiral. I kept complaining and kept being told it was all in my head. In little less than a year I went from 140lbs to 235lbs after having my gallbladder out and then a hysterectomy four months later. Thirteen years, more than 25 doctors later, I’ve just now been told I have PCOS, hypothyroid and adrenal insufficiency. My hormones are a mess. I feel so angry and betrayed by the medical industry. I’m hoping I can turn it around now that I have a doc willing to listen. Thank you for putting yourself out there and sharing what you’ve learned. Maybe it will help others from ending up suffering for so long.


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