Mary's PCOS Treatment FAQ |
Copyright © 2006 Mary Kate Roget |
Contents |
Introduction |
This is information that I have collected on PCOS treatments, and I wanted to share it. Who am I? I am Mary Kate Roget. I am not a doctor. I am trying to learn as much as I can about PCOS, just like many of you are. If you find an error or omission on this page, I will appreciate Disclaimer: I am not a doctor. Consult your doctor before using any treatments. Many treatments listed here are extremely dangerous. Nothing in the FAQ should be taken as advice. Please use this information only as a starting point for doing more research and for topics to discuss with your doctor. If your doctor disagrees with these treatments, look up the published studies and show them to her. Everything here has at least some studies or other data to back it up, or it's a mistake. If you are interested in a study reference for any statements made in this FAQ, Treatment is important because, according to webmd.com, "The risk of developing diabetes is five times greater in women with PCOS. These women will also develop diabetes at a younger age." "There is no cure for PCOS, but controlling it lowers your PCOS risks of infertility, miscarriages, diabetes, heart disease, and uterine cancer." I have a bias. I want to look and feel healthy. I am not so much interested in simply inducing ovulation as I am in weight loss and appearance. This FAQ does not cover fertility issues. Also, I do not have high blood sugar or triglycerides, yet. So, I do not consider treatments that increase insulin secretion to be beneficial for someone like me, even though they may be beneficial for anyone who does have high blood sugar. This FAQ does not cover surgical options. |
Information Sources |
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Biochemical Features in PCOS |
Increased Fasting Insulin Decreased Glutathione Lipolytic Catecholamine Resistance Possible Adrenal insufficiency There is conflicting evidence for some of the features listed above. Everyone will have different features and symptoms. Many women will not have high blood sugar, for example. That may come in later stages after insulin resistance takes its toll. As one study put it: "Polycystic ovary syndrome describes a conformational ovarian state that may be the final common manifestation of several pathogenic pathways." These features share many features in common with diabetes and hyperinsulinemia. If you know of other PCOS features not listed above, please |
Diagnostic Criteria |
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Two definitions of PCOS are commonly used today[1]:
Despite the name, not all women with PCOS have polycystic ovaries and they are unnecessary for diagnosis. "Witness the changing definition of 'polycystic ovaries' and the 10% to 30% of women with PCOS who do not demonstrate polycystic ovaries on ultrasound."[2] "In the full-blown syndrome (classic PCOS), the clinical symptoms provide the most powerful indication and the association of the three components (hyperandrogenism, anovulatory dysfunction and metabolic abnormalities) has a strong diagnostic potency."[3] Hyperandrogenism is a key feature, yet "only half of women with PCOS exhibit elevated serum free T concentrations."[4] So, blood tests are great and help in understanding what is going on but they are actually not necessary to diagnose PCOS, except maybe to rule out other causes. References: [1] The Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003
consensus on diagnostic criteria and long-term health risks related to polycystic
ovary syndrome (PCOS). Hum Reprod. 2004 Jan;19(1):41-7. |
Treatment Target |
The treatment target is basically to reverse the features listed above. Some features are more upstream from others. Elevated C-Reactive Protein can be caused by increased TNF-alpha. Low SHBG is probably a consequence of hyperinsulinemia which inhibits its production. TNF-alpha may increases MMP-9. High blood sugar results, over time, from insulin resistance and hyperinsulinemia. But, many are closely interrelated, and there is no consensus as to what exactly is the root cause. High insulin causes high testosterone, and the reverse is also true. High TNF-alpha causes increased insulin, and the reverse is also true. Most of these features are so tightly related that if you treat one, you are likely to improve all the others. Lowering lipid levels, improves antioxidant status and decreases inflammation and increases insulin sensitivity. Insulin inhibits SHBG production, so anything which lowers insulin levels should also improve SHBG levels. There are many more examples. The one most people know is that if you lower insulin, you lower testosterone, and the reverse is true to a lesser extent. Insulin resistance appears to be the most important feature, but it does not explain everything. The two main targets are androgens and insulin. Most treatments are targeted at blocking androgens and increasing insulin sensitivity. Increasing insulin sensitivity is good for everyone, and it appears to be especially important for those of us with PCOS. You cannot have too much insulin sensitivity. Insulin sensitivity generally decreases with age and is why the risk of developing Type 2 diabetes increases with age. There is no single treatment that will give you perfect insulin sensitivity. There are many treatments that increase insulin sensitivity somewhat and to varying degrees. One should do as much as possible to try to increase insulin sensitivity and not pin your hopes on any single treatment. Depression and bipolar disorder are common in PCOS. These neurological symptoms have some features in common with PCOS: insulin resistance, high blood sugar, increased TNF-alpha, C-Reactive Protein, homocysteine, lowered omega-3 fatty acids, lowered Magnesium, and dysregulation of the hypothalamo-pituitary-gonadal axis. There is evidence that treating these features can improve depression, along with PCOS. There is also evidence that any effective treatment for PCOS will improve depression as well. See my depression & mood disorder references page. |
Treatments |
Doses listed below are per day. Many supplements are better to take in divided doses, 2 or 3 times a day, as many have a short half-life. You may notice that some doses listed here are much higher than the recommended daily value. RDA or RDI dosages for nutrients are the amount needed to prevent disease. RDI dosages are not designed to treat any disease or disorder like PCOS or diabetes. If you want any vitamin, drug, herb or nutritional supplement to treat PCOS, you must be aware of the dose required for an effect. At the same time, be aware of doses that may be toxic. If your supermarket multivitamin has 1mg of something, and here is listed 1000mg, it should make you concerned, and you should seek out more information and ask your doctor. However, just because your multivitamin contains something, does not mean that it will have any effect. If a multivitamin's dose for a particular nutrient is nowhere near the dose shown to benefit PCOS, it is probably completely worthless as a treatment for PCOS. Each treatment is given my personal and totally subjective star rating based on 5 stars. I try to base the ratings on the published studies rather than on antidotal evidence. There may be treatments here that get very enthusiastic praise from people, and I only give them three stars or less. In that case, it's because I could not find studies to support the praise, but that doesn't mean the proponents are wrong. It has been noted that several treatments for insulin resistance take more than a month, to several months, to see any benefits. In fact, some treatments, especially those that increase insulin sensitivity may initially, briefly, increase body weight due to anabolic and fat storage effects of insulin. Keep that in mind if you are judging the effectiveness of any new treatment. Some treatments include references, others were omitted to save space. I have collected over 400 references. If you are interested in a study reference for any statements made in this FAQ, Disclaimer: I am not a doctor. Consult your doctor before using any treatments. Many treatments listed here are extremely dangerous. Dosages below may be inaccurate. Please use this information only as a starting point for doing more research and for topics to discuss with your doctor. |
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Exercise: Lifestyle, diet and exercise can be very effective and are often considered the first-line treatment. If you're not exercising or you're eating a high-calorie or high-glycemic-index diet, that's the first thing to correct. Lifestyle changes have been shown to be more effective than Metformin. Of course, you can add other treatments on top of lifestyle for further improvement. Exercise has been shown to increase insulin sensitivity and reduce abdominal fat, blood sugar, and insulin levels. It is much better to exercise a little every day than a lot every few days. Among other things, exercise will burn off blood sugar and prevent it from staying elevated and causing inflammation and all it's other negative effects. You cannot make up for skipped days and the effect on blood sugar by working out harder the next day. In the study referenced below under Metform, the lifestyle group engaged in physical activity of moderate intensity, such as brisk walking, for at least 150 minutes per week. Cardio training and resistance training each show destinct benefits. The quote below is from a review article that talks generally about many ways to increase insulin sensitivity. You can read the full article here. Quote: "Even an exercise routine as simple as incorporating brisk walking four times weekly
dramatically improves endurance fitness, decreases body fat stores, tends to reduce food
consumption, and decreases insulin resistance. Based on available evidence
it is likely an optimal program for improving insulin sensitivity might,
in addition to an aerobic component like walking, aim even more specifically
to selectively deplete body fat Reference: Kelly GS. et al. Insulin resistance: lifestyle and nutritional interventions. Altern Med Rev. 2000 Apr;5(2):109-32. Quote: "The results obtained indicated that ovarian morphology was almost normalised in the PCO exercise group; NGF mRNA and protein concentrations were normalised in the PCO exercise group; high numbers of NGF receptor expressing cells in PCO ovaries were lowered by exercise; and the number of immunopositive cells of the different AR subtypes were all reduced after exercise in the PCO group." Reference: Manni L, et al. Effect of exercise on ovarian morphology and expression of nerve growth factor and alpha(1)- and beta(2)-adrenergic receptors in rats with steroid-induced polycystic ovaries. J Neuroendocrinol. 2005 Dec;17(12):846-58. More References: |
Lower Carb Diet: Low glycemic index foods are more slowly absorbed and cause less insulin to be released. Quote: "On the balance of evidence to date, a diet low in saturated fat and high in fibre from predominantly low-glycaemic-index-carbohydrate foods is recommended [in the dietary management of PCOS]." Reference: Marsh K, et al. The optimal diet for women with polycystic ovary syndrome? Br J Nutr. 2005 Aug;94(2):154-65. Quote: "A moderate reduction in dietary carbohydrate reduced the fasting and postchallenge insulin concentrations among women with PCOS, which, over time, may improve reproductive/endocrine outcomes." Reference: Douglas CC, et al. Role of diet in the treatment of polycystic ovary syndrome. Fertil Steril. 2006 Mar;85(3):679-88. Monounsaturated Fats or polyunsaturated fat should replace Saturated fat (For example: replace butter with olive oil). Diets high in monounsaturated fats have been shown to increase insulin sensitivity. It will also slow digestion and lower the overall glycemic index of a meal. High fiber diets increase SHBG which binds to and lowers free testosterone. Fiber can lower PAI-1. Various fibers have also been shown to lower cholesterol and blood lipids. Unrefined, whole foods will generally have a lower glycemic index, more fiber, and more nutrients. Adequate protein diets have benefits. Low protein diets are shown to contribute to insulin resistance and adversely affect body weight. Compared to low protein diets, higher protein diets have been shown to increase weight loss and to help maintain that weight loss. Protein also slows digestion and lowers the overall glycemic index of a meal. Unfortunately, a high protein diet was shown to lower SHBG. Interestingly, carb intake itself was not associated with SHBG levels in one study. I don't know if this works, but if you're Starving? Try the "Two Gram Cure." |
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Antiandrogens: Antiandrogens are not covered in depth here. There's a lot more to know than I'm going to cover. Antiandrogens have been shown to substantially improve virtually every symptom of PCOS. No other treatment is more effective for hirsutism or hair loss. In fact, most other treatments are really not very effective for hair. Nonetheless, they have their drawbacks and side effects. Your doctor would probably have you take an OCP with an antiandrogen because of the birth defects they can cause, especially in males (males need those androgens). So, they are not an option if you are TTC. When using antiandrogens for androgenic hairloss, it's important to understand that the hair cycle is long, and it is practically impossible to see new hair growth before 3 to 6 months. Also, the hair cycle progresses through its stages in order. Hair enters the resting (telogen) phase, then the hair is a shed before a new hair starts growing (anagen). Any hair in telogen must fall out before it will start growing again. This means that any hair loss treatment that works will probably be associated with initial shedding as new hairs come out of telogen. This is naturally alarming to see. If you indeed have androgenic hair loss, and you are using something that is proven to treat androgenic hair loss, like any strong antiandrogen, and you are worried it is making things worse after a few weeks, it's probably only temporary (of course, you should ask your doctor in case it's something else). Also, if you started using a new treatment yesterday or last week and it looks like you have more hair, you're kidding yourself - it's the humidity or your shampoo or you're just in a good mood. The lesson here is, use something that is proven to work and then try not to think about it for a few months. Don't think you're going to try something for a couple weeks just to see if it works. A lot of studies on hair loss and hirsutism sound impressive, but really they aren't. In medical studies, the words "effective" and "significant" may only mean there was a tiny effect that was statistically significant. The word "significant" does not mean "a lot," it only means the effect, however small, was not due to chance. So, you can read a study that claims "this was an effective treatment for hair loss", and "there was significant new hair growth", and what really happened was a tiny, "non-cosmetic" improvement that you can't even see. The improvement could be a lot, but you have to read the details to know. It's my speculation, and from reading forums, that one could use an antiandrogen temporarily for, say, a year or two, and then taper off and stop taking it. After some time on an antiandrogen, you would reverse a lot of the hyperandrogenic symptoms. Then you could stop and hopefully the symptoms would not come back as long as you continued with your other treatments to keep your weight, insulin and androgens low, like with diet, exercise and insulin sensitizers. Because, if you're androgens are low enough and being kept in check with other treatments, your symptoms shouldn't come back to any large degree. At least, I hope. I could be wrong and I don't have proof. Flutamide (Eulexin) has many articles demonstrating liver damage and death. It's too bad because Flutamide is a very potent antiandrogen. However, in almost every case they are at doses above 350mg/day. Several studies show efficacy in PCOS at low to very low doses of flutamide (62mg to 250mg per day), and suggest that these doses are safe. If you take it, your doctor will probably watch your liver closely with blood tests. There is no doubt that it can greatly improve PCOS symptoms. Flutamide is the strongest antiandrogen and the most effective treatment for hirsutism and hair loss that I know of (except maybe for Dutasteride). Quote: "After only 6 months of therapy, flutamide caused a maximal reduction in the hirsutism score to a value within almost normal range; during the same period, spironolactone caused only a 30% reduction of the hirsutism score. Whereas flutamide caused a dramatic (80%) decrease in total acne, seborrhea, and hair loss score after only 3 months of therapy, spironolactone caused only a 50% reduction in acne and seborrhea, with no significant effect on the hair loss score." Reference: Cusan L. et al. Comparison of flutamide and spironolactone in the treatment of hirsutism: a randomized controlled trial. Fertil Steril. 1994 Feb;61(2):281-7. The enzyme your liver uses to process Flutamide is the same enzyme used to process caffeine, Prozac and Echinacea. It may be a good idea to avoid things that inhibit the CYP1A2 liver enzyme, if you are taking Flutamide. However, even though caffeine is metabolized by CYP1A2, it also increases the activity of CYP1A2 at the same time, and thus "caffeine increases its own metabolism". So, whether caffeine is good or bad to take with Flutamide is unclear - I doubt it matters. One study notes that "CYP1A2 index was 33% decreased in women who used oral contraceptives." Also, the antioxidant carotinoid, Astaxanthin has been shown to be a strong inducer of CYP1A1 and CYP1A2 liver enzymes. This implies Astaxanthin may help detoxify the byproducts of Flutamide. But, I have no idea if any of this matters in practice, and I may be confused. Spironolactone (Aldactone) is a good antiandrogen. It is safer than Flutamide (depending on the dose), but typically a little less effective. This drug is a potassium sparing diuretic and it also blocks aldosterone. In contrast to the glowing reference for Flutamide above, several studies showed no significant difference between Flutamide and Spironolactone - both were effective. Dutasteride (Avodart) is a 5 alpha-reductase inhibitor (both types 1 and 2) that reduces dihydrotestosterone (DHT). It is the most potent 5-ar inhibitor and will greatly lower DHT levels. Unfortunately, there are not many studies on Dutasteride yet and none specifically on hirsutism. The following case study shows a full reversal of androgenic hair loss. Quote: "After 6 months of therapy, significant improvement was observed and after 9 months the clinical diagnosis of androgenic alopecia could no longer be made in this patient." Reference: Olszewska M, et at. Effective treatment of female androgenic alopecia with dutasteride. J Drugs Dermatol. 2005 Sep-Oct;4(5):637-40. Finasteride (Proscar or Propecia) is also a 5 alpha-reductase inhibitor (type 2 only). Finasteride is less potent than Dutasteride. It probably has the least side effects, and is the least effective, but studies show that it has merit. Saw Palmetto extract (Serenoa Repens) may have effects similar to Finasteride. Two studies suggest it may be beneficial for hirsutism based on Saw Palmetto's ability to inhibit 5 alpha-reductase. A recent study comparing Saw Palmetto to Finasteride found Saw Palmetto was completely ineffective. Previous studies showed some effect, however. I have grouped this here with the antiandrogens, but I'd only give it 3-stars. My feeling is, if you want to take a 5-ar inhibitor, take one that really works. |
Metformin: (Metformin XR, Glucophage XR) Metformin is a glucose lowering and insulin sensitizing drug for the treatment of diabetes. Metformin has been shown repeatedly in published studies to increase insulin sensitivity, lower androgens, lower C-Reactive Protein, lower PAI-1, and raise D-Chiro-Inositol and SHBG in PCOS. Numerous studies show improvement in most every PCOS symptom with doses of 1500-2500mg. There are too many studies to list. Virtually every study on PCOS in the last 10 to 15 years discusses Metformin. Anecdotal reports in various PCOS forums suggest 2000mg or more may be necessary for some. Unfortunately, Metformin lowers folate and B12, and raises homocysteine and TNF-alpha. So, it would be wise to supplement Folate and B12, and possibly other homocysteine lowering agents, like B6, along with agents to lower TNF-alpha. Also, it may be unwise to supplement folate without B12, as folate can mask symptoms of B12 deficiency. Often, benefits begin to appear after months, not weeks. Metformin is a very safe drug. However, it does have some degree of toxicity. Kidney toxicity, and less commonly, liver toxicity, is possible. Reference: Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. In the study above, involving 3,234 people over an average of 2.8 years, Metformin (1700mg) alone was compared to a placebo, and to lifestyle intervention (diet & exercise). The results showed that lifestyle decreased the incidence of diabetes by 58%, and Metformin by 31%. So, Metformin was good, but diet and exercise was better. The number of deaths during this study was: Deaths (no./100 person-yr): Placebo:0.16 Metformin:0.20 Lifestyle:0.10 The number of deaths was not statistically significant. What's interesting, if you Google Metformin and life extension, you will find a lot of discussion about using Metformin to extend lifespan. There are actually people taking it who do not have diabetes or PCOS and are perfectly healthy and they take it because insulin sensitivity is one of the most important markers of lifespan. Metformin was shown to extend lifespan and decreased the incidence and size of mammary tumors in mice. Reference: Anisimov VN, et al. Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Exp Gerontol. 2005 Aug-Sep;40(8-9):685-93. To avoid nausea, it may help to start with a low dose and increase the dose very slowly. Nausea often goes away with time. The 'XR' form may also help reduce nausea. If you start out at some dose and experience nausea then talk to your doctor about lowering your dose temporarily and slowly increasing after you give your body a chance to adjust. Just because you can't tolerate a particular dose now doesn't mean it's just wrong for you or that you will never be able to tolerate it. Maybe, maybe not, but unless you give it a chance, you won't know. Metformin may also cause diarrhea. A study notes that, unlike nausea, diarrhea may occur later even when the dosage has been stable over a long period. Calcium supplementation may reverse the possible metformin-induced decrease of B12 absorption. Reference: Bauman WA, et al. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care. 2000; 23:1227-1231. Quote: "Only the obese subgroup showed a dose relationship (1.5 and 3.6 kg in 1500- and 2550-mg groups, respectively; P = 0.04). ... Weight loss is a feature of protracted metformin therapy in obese women with PCOS, with greater weight reduction potentially achievable with higher doses." Reference: Harborne LR, et al. Metformin and weight loss in obese women with polycystic ovary syndrome: comparison of doses. J Clin Endocrinol Metab. 2005 Aug;90(8):4593-8. Epub 2005 May 10. |
Actos: (Pioglitazone) Avandia: (Rosiglitazone) These are insulin sensitizing diabetic drugs. These have been shown repeatedly to increase insulin sensitivity, SHBG and other hormonal parameters, and improve PCOS symptoms. They were shown to decrease PAI-1. They can be used in combination with Metformin since they have a different mode of action. The combination has been shown to help PCOS subjects who were resistant to Metformin therapy alone. These are a class of drug called thiazolidinediones. Actos and Avandia appear to be safer than another discontinued thiazolidinedione, Rezulin. This class of drug is relative new. They are prescribed less often than Metformin for a couple reasons. There are still fears of toxicity and unknown long-term side effects. Also, these drugs do not appear to improve weight as Metformin can, and there may be weight gain with Avandia. References: |
Byetta: (Exenatide) Byetta's active ingredient, Exenatide, works by mimicking the effects of a human hormone called GLP-1, which is normally released after meals, stimulating digestion and insulin production. GLP-1 also discourages the liver from producing too much sugar. Studies show it increases insulin sensitivity. Stimulating insulin production is bad, unless you're not producing enough insulin. Reducing hepatic glucose release is good and is one of the things Metformin does. As long as the increased insulin is not more than necessary, and is only increased when there is not enough, it should be all good. Byetta is currently being tested for PCOS in a clinical study. We will know more when further studies are published. A major downside is that this is taken by injection just before breakfast and dinner. |
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Oral Birth Control Pills: OCPs are not covered in-depth here either. There are some good ones that are more antiandrogenic than others. For many years, oral contraceptives were the standard, first-line, treatment for PCOS. They can actually help with almost every symptom. They are not worthless, and some are better than others. Some have evidence of increased insulin resistance. So, you need to shop around if you want this treatment. Unfortunately, these may raise C-Reactive Protein and deplete Vitamin C. Perhaps the biggest reason to take these is that they can significantly increase SHBG, which decreases free testosterone. |
Precose: (Acarbose) Miglitol: (Glyset) These prescription drugs have been shown to be effective in the treatment of PCOS by decreasing glucose load which resulted in decreased insulin response, lower androgens and LH, and increased SHBG. These drugs slow the digestion of starches you eat by inhibiting alpha-glucosidase. You take them with the first bite every meal. You typically start out at a low dose until you get used to it and work up to 50-100mg per meal. Side effects were frequent abdominal distension, diarrhea and flatulence. Side effects may lessen over time. If you take these drugs it is important to understand that they will slow down the digestion of most starches and complex sugars, but not glucose, fructose or corn starch. References: Quote: "This is the first report showing a reduction of the acne/seborrhoea score in hyperinsulinaemic patients with PCOS treated with acarbose. This improvement was associated with a significant decrease of the insulin response to oral glucose load and of LH and androgen serum concentrations and with a significant rise of sex hormone binding globulin concentration." Penna IA, et al. Acarbose in obese patients with polycystic ovarian syndrome: a double-blind, randomized, placebo-controlled study. Hum Reprod. 2005 Sep;20(9):2396-401. Epub 2005 Jul 8. Quote: "A low dose of acarbose administered to obese patients with PCOS promotes a reduction in free androgen index and BMI and an increase in SHBG, with improvement of hirsutism and of the menstrual pattern, and is well tolerated by patients." |
D-Chiro-Inositol: This is shown in several studies to improve insulin sensitivity and PCOS symptoms. Why did the owner of the patent on its use for PCOS, Insmed, decide not to market it? This is Insmed's statement on record: "In recently completed clinical trials in patients with PCOS, INS-1 [(D-Chiro-Inositol)] was safe and well tolerated but did not achieve statistical significance on its primary efficacy measures. Although an overall increase in ovulation rates was not achieved, an increased number of pregnancies occurred in the INS-1 treated patients." This is really all we know. This was surprising since there are several other studies which found it was effective, including Insmed's previous phase I and IIa studies which involved more than 1000 subjects. Off record, the company is rumored to be trying to market DCI as a dietary supplement. Also, the doctor who discovered DCI's involvement in insulin action, Dr. Joseph Larner, told me by email that he is trying to make it available as a dietary supplement. The company is also reported to have said, off record, that the reason to discontinue DCI was a business decision. As late as Feburary 2006 it continues to be studied in relation to PCOS. I suspect that the business decision to discontinue FDA approval may be because it is not more effective than Metformin, or because you could take 3x the amount of Pinitol and get the same effect. Often (in studies that showed effectiveness), benefits began to appear after months, not weeks, as is the case with Metformin. D-Chiro-Inositol is something that your body makes. Some foods have it, but in minute amounts unless it is concentrated. The body will convert myo-inositol (the common form of inositol) to DCI. There is one study and one patent that suggests myo-inositol can help with insulin sensitivity too. But, it is also known that those with diabetes and PCOS are often inefficient at converting myo-inositol to D-Chiro-Inositol. This results in a higher ratio of myo-inositol to D-Chiro-Inositol. Pinitol (methyl-D-chiro-inositol), the methyl form of DCI, appears to be converted 33% to DCI. That says that 3600mg of Pinitol should be equivalent to 1200mg DCI. Reference: Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med. 1999 Apr 29;340(17):1314-20. Quote: "D-Chiro-inositol increases the action of insulin in patients with the polycystic ovary syndrome, thereby improving ovulatory function and decreasing serum androgen concentrations, blood pressure, and plasma triglyceride concentrations." More References: |
NAC: (N-Acetyl-Cysteine) NAC is the acetylated form of the amino acid L-Cysteine. Several studies show benefit in PCOS at 1200-1800mg. NAC has many other studies showing benefit in diabetes. It can improve insulin sensitivity. It lowers TNF-alpha, suppresses MMP-2 and MMP-9 and inhibits VEGF. It increases Glutathione. It is a potent antioxidant. It can reduce homocysteine. Normally it is a good idea to take amino acids on an empty stomach so they will not compete for absorption with other protein. However, NAC can cause nausea if taken on an empty stomach, which shouldn't happen if you take it with food in divided doses. As of this date, there are no adequate studies of NAC administration in pregnancy. There are at least three human studies that used 1800mg NAC which showed positive results. The first study listed below found that doses below 1200mg were beneficial, but in healthy people, 1200mg acted as a pro-oxidant and may lower glutathione. However, other studies at these doses and higher, including ones that post-date that study, found the opposite effect. Furthermore, PCOS is associated with an increased oxidative state, and if NAC can improve the parameters in PCOS, then it seems likely it would lower that oxidative stress caused by PCOS. NAC may increase urinary zinc excretion. A molybdenum deficiency (which is very rare) can cause an accumulation of sulfite from the catabolism of L-cysteine. References: Effects of oral N-acetylcysteine on cell content and macrophage function
in bronchoalveolar lavage from healthy smokers. Eur Respir J. 1988 Jul;1(7):645-50. Quote: "Combination of CC [clomiphene citrate] and NAC significantly increased both ovulation rate and [pregnancy rate] in women with CC-resistant PCOS (49.3% vs. 1.3% and 21.3% vs. 0%, respectively)." Kilic-Okman T, et al. N-acetyl-cysteine treatment for polycystic ovary syndrome.
Int J Gynaecol Obstet. 2004 Jun;85(3):296-7 Quote:"Insulin [area under curve] after [oral glucose tolerance test] was significantly reduced, and the peripheral insulin sensitivity increased after NAC administration, whereas the hepatic insulin extraction was unaffected. The NAC treatment induced a significant fall in T levels and in free androgen index values. In analyzing patients according to their insulinemic response to [oral glucose tolerance test], normoinsulinemic subjects and placebo-treated patients did not show any modification of the above parameters, whereas a significant improvement was observed in hyperinsulinemic subjects. CONCLUSION(S): NAC may be a new treatment for the improvement of insulin circulating levels and insulin sensitivity in hyperinsulinemic patients with polycystic ovary syndrome." |
Lipoic Acid: (Alpha Lipoic Acid) Many studies show improved insulin sensitivity at doses of 600-1800mg. Lipoic acid lowers TNF-alpha and suppresses MMP-9 and prevents increased VEGF. In some studies, doses below 600 were found to be ineffective, where higher doses were effective. It is a potent antioxidant. The other benefits are too numerous to list. This is sometimes characterized as an insulin mimic. If it is available, R-Lipoic Acid would be a better choice, and half the dose could be used. Lipoic Acid can compete with biotin, so you may want to take extra biotin with this. Lipoic acid has a short half-life and a couple studies suggest that sustained release tablets may have an advantage. However, another theory says that immediate-release (or "pulsed release") lipoic acid has an advantage by overwelming the liver and thus increasing plasma levels since it has such a high first-pass metabolism. Several studies show that when GLA is combined with Lipoic Acid it strongly enhanced the glucose lowering and insulin sensitizing effects beyond using either one individually. Lipoic Acid has been suggested as a treatment for depression in metabolic disorders. |
Fish Oil : (Eicosapentaenoic Acid/Docosahexaenoic Acid, EPA/DHA) Many studies show increased insulin sensitivity, decreased TNF-alpha, MMP-2, MMP-9 and other inflammatory cytokines, improved blood lipids. Numerous studies show improvement with omega-3 fatty acids in depression. The benefits are too numerous to list. All omega-3 oils are not the same. There are a huge number of studies showing a huge range of benefits from fish oil and especially from the EPA and DHA fatty acids. Other oils, like flaxseed oil, have far less evidence of benefits, and nowhere near the degree of benefit seen from fish oil. Despite being an omega-3 oil, Flax does not contain the omega-3 fatty acids EPA and DHA found in fish oil. Many studies show benefits from these specific isolated fatty acids. Flax primarily contains the omega-3 fatty acid alpha-linolenic acid which is partly converted to EPA by the body, and virtually none is converted to DHA. The EPA created by taking Flax can have some of the same benefits as Fish oil. However, fish oil will more effectively raise blood levels of EPA, and fish oil includes DHA which has shown similar, and distinct benefits. Flax lignands (found in flaxseeds not pure flax oil) may have additional benefits, however. It's probably best to take a fish oil concentrate to increase the amount of EPA and DHA in the fish oil and avoid excess vitamin A and D. Some supplements have names like "Max EPA" or "Super EPA". Using a concentrate will require far fewer pills than whole fish oil. There have been no reports of serious adverse events in those taking EPA supplements, even up to 15 grams daily, for prolonged periods of time. Those side effects that have been reported include mild gastrointestinal upsets such as nausea and diarrhea, halitosis, eructation, "fishy" smelling breath, skin and even urine. The blood-thinning effects can cause occasional nosebleeds and easy bruising. For many people, the gastrointestinal side effects often disappear after a few weeks. If you are bothered by the gastrointestinal effect, it is sometimes recommended to start with one pill per day, and very slowly increase the number of pills over weeks. Krill Oil is another option that may have similar benefits. The studies on Krill Oil are impressive, but I doubt any are peer-reviewed. |
Calcium: Vitamin D3: (Cholecalciferol) A study using Calcium and Vitamin D showed improved PCOS symptoms. Their are many other studies on using both together, and using them independently which show improvement in diabetes, insulin resistance, hyperinsulinemia, and glucose tolerance. Several studies show impressive weight loss with calcium supplementation. Vitamin D is also effective at lowering TNF-alpha. Vitamin D deficiency increases C-Reactive Protein, MMP-9 and MMP-2. Calcium may also be helpful in treating PMS. Coral calcium, which also contains magnesium, has gotten a lot of hype but so far there is no evidence that it is better absorbed or has any other benefits over the citrate or some other forms which are proven to be well absorbed. If you are allergic to shellfish, the Mayo Clinic says coral calcium can trigger an allergic reaction. Some people claim there is a potential for coral to contain heavy metals. Low levels of lead were measured in some samples of coral calcium, but they were within FDA limits. Calcium is not absorbed very well, in general. The absorption of Calcium Bisglycinate (44% absorption) > Calcium Citrate Malate (CCM) (36%) > Calcium Citrate (24%) > Calcium Carbonate (23%) > Hydroxyapatite (17%) > Calcium Hydoxide/Oxide (10%). You can't really compare the percents listed here because some of them are the percent absorption with meals and others were measured on an empty stomach. But, it should give you a rough idea. There is some evidence that Calcium carbonate cannot be absorbed and utilized until it is converted to calcium chloride in the stomach, and using stomach acid to convert it will interfere with B12 absorption and digestion of foods. The absorbability of calcium citrate is between 20% and 100% better than calcium carbonate, depending on who you ask. A study in JAMA found that calcium absorption from supplements increases about 10% when taken with meals. However, this may be less of a factor with Calcium Citrate than to other forms, as Citrate basically comes with its own acid to aid digestion. It's better to take 500mg or less at a time. The more you take at once, the less you absorb. As you take more, absorption becomes less and less efficient. Taking calcium with meals supposedly reduces the risk of kidney stones. Reference: Vitamin D and calcium dysregulation in the polycystic ovarian syndrome. Steroids. 1999 Jun;64(6):430-5. Quote: "Vitamin D repletion with calcium therapy resulted in normalized menstrual cycles within 2 months for seven women, with two experiencing resolution of their dysfunctional bleeding. Two became pregnant, and the other four patients maintained normal menstrual cycles. These data suggest that abnormalities in calcium homeostasis may be responsible, in part, for the arrested follicular development in women with PCO and may contribute to the pathogenesis of PCO." |
Chromium: Many studies show strong evidence of improved insulin sensitivity. Chromium may reduce fasting insulin levels. Several studies show increased fat loss, yet other studies found no effect on weight. Deficiency can cause insulin resistance. Chromium may lower total cholesterol and LDL-cholesterol. Chromium may have synergy when taken with Biotin. Several studies show no effect from 200mcg per day, while studies on 800 to 1000mcg have shown effect. In vitro studies and high-dose in vivo animal studies found Chromium Picolinate (as opposed to Polynicotinate or other forms) increased chromosomal damage. Other forms of Chromium were shown not to cause this DNA damage. However, in vivo human studies using various measures of DNA damage have not yet found Chromium Picolinate to cause this DNA damage. If you choose to take Chromium, you might as well avoid the Picolinate form and instead take the Polynicotinate, GTF, or Chelavite (glucose-tolerance-factor, chromium-niacin, or chromium-niacin-amino acid chelate) forms. The Chelavite form may be the most absorbable form. Chromium was recently studied specifically for PCOS. Quote: "Trivalent chromium (1000 microg), as chromium picolinate, given without change in diet or activity level, caused a 38% mean improvement in glucose disposal rate in five obese subjects with polycystic ovary syndrome who were tested with a euglycemic hyperinsulinemic clamp technique. This suggests that chromium picolinate, an over-the-counter dietary product, may be useful as an insulin sensitizer in the treatment of polycystic ovary syndrome." Reference: Lydic ML, et al. Chromium picolinate improves insulin sensitivity in obese subjects with polycystic ovary syndrome. Fertil Steril. 2006 Jul;86(1):243-6. Epub 2006 May 30. Chromium has been studied as a treatment for depression in metabolic disorders. |
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Oral Progesterone: Natural Progesterone Cream: I could not find many clear descriptions of its benefits or what improvements to expect in PCOS symptoms. Many people are enthusiastic about Natural Progesterone Cream and find it very helpful, and those people would give it a higher rating than I did. Oral Progesterone appeared to work better in one study that compared the Cream and Oral forms, but that may have been only because of the dose of cream used. There is evidence that both can lower LH and increase SHBG. There is some evidence that they may improve insulin levels as well. Several studies suggest it does not improve androgen levels. It has potential to help with many PCOS symptoms. It appears most useful for inducing ovulation and improving menstrual regularity. A study that used the cream at 100mg twice a day appeared to work better than 50mg twice a day. But, you don't use Progesterone every day of the month. If you plan to use this, you will need more information than is discussed here. I am not a big fan of this treatment, partly because the theory of Progesterone deficiency does not appeal to me as much as the theory of reduced sensitivity to progesterone and estrogen. Personally, I would rather treat the sensitivity problem rather than treating it as a deficiency. But, I could be wrong. Reference: Vaginal progesterone administration in physiological doses normalizes raised luteinizing hormone levels in patients with polycystic ovarian syndrome Gynecol Endocrinol. 1992 Dec;6(4):275-82. Quote: "The mean serum LH concentration had fallen significantly after 8 days of treatment, and continued to fall progressively until the end of progesterone administration. Serum LH concentrations had fallen into the normal follicular phase range by 14 days." |
Green Tea: (epigallocatechin gallate, EGCG) Many studies show improved insulin sensitivity. It lowers TNF-alpha and MMP-2 and MMP-9. It is a potent antioxidant. It may increase SHBG. A study shows 90mg EGCG taken 3 times per day resulted in impressive weight loss. EGCG (epigallocatechin gallate) is a major polyphenol or catechin in green tea that has been tested in may studies and is thought to be one of the most active ingredients. Every Green Tea extract will have a different concentration of EGCG. Some Green Tea extracts are only 10% EGCG. Some contain caffeine and some are (mostly) decaffeinated. The study below tested green tea extract in PCOS and found no significant effect. I haven't read the full study. I'm sure they studied it because they thought it would be effective because of the many of studies showing increased insulin sensitivity and other benefits in humans and animals. If I'm going to weigh all the evidence, I can't throw out green tea because of one study. It's certainly an interesting result and it begs for an explanation. Reference: Chan CC, et al. Effects of Chinese green tea on weight, and hormonal and biochemical profiles in obese patients with polycystic ovary syndrome--a randomized placebo-controlled trial. J Soc Gynecol Investig. 2006 Jan;13(1):63-8. |
Flaxseed Lignans: These are phytoestrogens. This is not flaxseed oil, though you can find high-lignan oil. A study found "Three anovulatory cycles occurred during the 36 control cycles, compared to none during the 36 flax seed cycles." Lignans may increase SHBG. They may be 5 alpha-reductase inhibitors, although the evidence is not strong. These may have many of the same benefits as soy isoflavones. |
Soy Isoflavones: These are phytoestrogens. There is evidence these can increase SHBG. They may inhibit TNF-alpha. Soy Isoflavones have been studied for prevention of breast cancer. However, there are few studies on their possible benefits in PCOS. One study shows it may contribute to menstrual irregularity. Most of the benefits are antidotal, but that may only mean the science needs to catch up. |
Cinnamon: The active chemical in Cinnamon is MHCP or methylhydroxychalcone polymer. This has been shown to lower blood glucose levels. Cinnamon has been in the news recently, but it has been known about for some time. The cinnamon used in the 2003 study in Diabetes Care was actually Cassia (Cinnamomum cassia) and not "true" cinnamon (Cinnamomum zeylanicum, or Cinnamomum verum). According to reports, the authors said the active agent is in all varieties sold as the spice. Cassia is cheaper and more common in the US. In the US, but not every country, Cassia is allowed to be sold and called Cinnamon. The authors suggested that 1/4 to 1 teaspoon daily may be useful for type 2 diabetes, but it's too soon to know for sure. Specifically, the study used 1, 3 or 6 grams of cinnamon, and all doses showed a response within weeks. It's recommended not to use cinnamon while pregnant, but I don't know why. Cinnamon was also found to lower triglycerides, LDL cholesterol, and act as an antioxidant. One study finds, "cinnamon supplementation does not improve glycemic control in postmenopausal type 2 diabetes patients." Other studies note the effect is only moderate. In the diabetes newsgroups, many people have tried it, people who watch their blood glucose very closely, and their results were nil, unimpressive, or even negative. References: Kannappan S, et al. Cinnamon bark extract improves glucose metabolism and lipid
profile in the fructose-fed rat. Singapore Med J. 2006 Oct;47(10):858-63 |
Biotin: Many studies show improved glucose tolerance and improved insulin sensitivity at doses of 8-16mg. These doses are much larger than you will find in a multivitamin. When taking large doses of any one B vitamin, it's usually recommended to take the rest of the B-complex with it. It may be a good idea to supplement with Biotin if you are taking either Lipoic Acid or Vitamin B5. |
Vitex: (Agnus Castus; Chasteberry; Chaste Tree) There are many enthusiastic users of Vitex who would give it a higher rating. Studies show it can increase LH, lower FSH, and thus raise progesterone. The raised progesterone raises the progesterone/estrogen ratio which may improve menstrual regularity and ovulation. Some experts argue that in the case of PCOS, Vitex works more by normalizing hormone levels than by simply increasing LH. It has also shown to help PMS symptoms. One study found reduced acne. The common advice is that this herb starts to work slowly over months. Vitex has also been shown to lower prolactin, which is increased in PCOS and may be partly responsible for infertility. There is evidence that Vitex decreases prolactin by virtue of it being a dopamine agonist. Prescription dopamine agonists like bromocriptine or cabergoline, have been shown to help induce ovulation, but they are not very effective at treating PCOS overall. The reason I did not give this a higher rating is the lack of evidence of weight loss, improved hirsutism, insulin sensitivity, or lowered insulin levels. Also, it may increase LH which is already increased in PCOS and lower FSH which is already decreased in PCOS. But, again, its been suggested that Vitex may not work this way in PCOS. Nonetheless, it appears to have benefits, and it may be that some of the benefits simply have not been studied yet. Interestingly, Vitex appears to stimulate melatonin secretion, which suggests that it could make a person sleepy. |
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Kidney Bean Extract: (Phaseolus Vulgaris Extract) This is a common ingredient in "carb blocker" type products. It inhibits the digestion of starch by inhibiting alpha-amylase. It has been shown in some studies to improve glucose metabolism. It may lower triglicerides. You take this with your first bite of each meal. A study by the Mayo Clinic confirmed that kidney bean extract can work to lower blood sugar, but that the commercial products they tested were not potent enough to have an effect. I don't know if there is an effective brand or not, or how much you would have to take. |
Vinegar: In a few studies, vinegar was shown to reduced the postprandial glucose and insulin responses probably by slowing digestion. Vinegar improves insulin sensitivity to a high-carbohydrate meal in subjects with
insulin resistance or type 2 diabetes. Diabetes Care. 2004 Jan;27(1):281-2. No
abstract available. |
Beta-Glucan/Guar Gum/Glucomannan: These are different types of soluble fibers. They can help lower postprandial insulin secretion and keep blood glucose lower by slowing gastric emptying. |
Pycnogenol: (pine bark extract) This has been shown to have some antidiabetic activity, including lowering blood glucose. It's a proven antioxidant. There is supposed to be a study showing that when combined with Metformin it lowers blood glucose more than with Metformin alone. The following study noted maximum improvement at 200mg, and no more improvement at 300mg. Liu X, et al. French maritime pine bark extract Pycnogenol dose-dependently lowers glucose in type 2 diabetic patients. Diabetes Care. 2004 Mar;27(3):839. Like Grape Seed Extract, this contains Procyanidins, so the two probably share
the same effects. |
Grape Seed Extract: The main ingredient in Grapeseed Extract are Procyanidins, which is the same as
Pycnogenol. Grape Seed Extracts may also contain a small amount of resveratrol.
There are only a few studies related to insulin in rats and in vitro. So, the
evidence is not strong, but taken with the evidence of Pycnogenol and it's better.
It's a great antioxidant. |
Sage: (Salvia officinalis) There are a couple in vitro and animal studies showing sage spice increases insulin sensitivity. Lima CF, et al. Metformin-like effect of Salvia officinalis (common sage): is
it useful in diabetes prevention? Br J Nutr. 2006 Aug;96(2):326-33. |
Taurine: Several studies show improved insulin sensitivity in animal models. Taurine can act as an antioxidant. It can decrease TNF-alpha and VEGF. It is neuroprotective. Taurine is lower in diabetics. Although the evidence is weak, it can increase the production of serotonin, and may be effective at treating bipolar disorder, depression, and anxiety. It has a calming effect on the nervous system. One study suggests that it may be beneficial to take Taurine with NAC. Because, on one measure of oxidation, Taurine by itself showed neutral or negative results, but when combined with NAC it was more beneficial than with NAC alone. Reference: N-acetylcysteine and taurine prevent hyperglycemia-induced insulin resistance in vivo: possible role of oxidative stress. Am J Physiol Endocrinol Metab. 2003 Oct;285(4):E744-53. Epub 2003 Jun. |
Magnesium: A study shows Magnesium deficiency in PCOS. There are many studies showing improvement in diabetes, hyperinsulinemia, and impaired glucose tolerance with doses of 500-2500mg. Deficiency can increase MMP-2 and MMP-9 activity, and TNF-alpha. A ratio of 2:1 (calcium to magnesium) is often recommended. In diabetes, and this probably includes PCOS, the recommendation is that the ratio should be closer to 1:1. Several studies show magnesium levels to be significantly reduced in depressed patients. Also, the calcium:magnesium ratio is often increased in depression. It has been shown to help treat several PMS symptoms, including mood changes. Magnesium can act as a laxative. If you plan to use a high dose, it may be a good idea to start slow. Some people cannot handle more than 300mg. Magnesium glycinate is a form that is supposed to be the most absorbable and have the least laxative effect. Magnesium citrate should have less of a laxative effect than magnesium oxide. |
GLA: (Gamma-Linolenic Acid found in Borage Oil or Evening Primrose
Oil) GLA is an omega-6 fatty acid normally made by the body by converting linoleic acid. Several studies show that when GLA was combined with Lipoic Acid it strongly enhanced the glucose lowering and insulin sensitizing effects beyond using either one individually. The strongest argument for its use in PCOS is in this combination with Lipoic Acid. There are conflicting studies on whether or not GLA by itself can increase insulin sensitivity. GLA can inhibit TNF-alpha and other inflammatory cytokines, which should, in theory, help improve insulin sensitivity, and is probably good for PCOS in any case. Several studies show benefit for diabetic neuropathy. When used alone, GLA may worsen lipid profiles. GLA has shown benefit in treating PMS in some studies. In other studies it has shown no benefits in PMS. If you take GLA, you might want to take an EPA/DHA fish oil supplement with it. A recent study suggested a slight increase in mammary carcinogenesis with GLA alone, but not when taken with fish oil. (Fish oil alone reduced the risk of mammary carcinogenesis.) Other studies suggested GLA may have anticancer effects. Several studies suggest GLA can act as a 5 alpha-reductase inhibitor, and thus lower DHT. However, those studies used free fatty acids, and were either in vitro or topically applied to skin. Digesting borage oil or evening primrose oil has no evidence of acting as a 5-alpha reductase inhibitor. |
Vitamin B5: (Pantothenic Acid; D-Calcium Pantothenate) This has been shown to lower blood lipids, increase fat loss, and dramatically improve acne at doses of 3-15gm. Such extreme doses may be unhealthy. These doses are much higher than the RDI. High-doses of B5 can lower Biotin. Besides that, the only known side effect of pantothenic acid at any dose is possible diarrhea. There is no known toxic dose of pantothenic acid. Normal doses may also improve insulin sensitivity, and inhibit TNF-alpha. B5 deficiency can cause depression and inadequate amounts of the brain chemical acetylcholine. B5 is needed for hormone formation. The argument made in some of the studies is that Pantothenic Acid is used by the body to make coenzyme-A. Coenzyme-A is necessary for lipid metabolism, and for hormone formation. Hormone formation is a high priority for the body, and the body will basically steal B5 away from other functions, like processing oil in your skin. If the theory is correct, since the body is making extra high levels of several hormones in PCOS, it seems possible that stores of B5 would be low. The adrenal glands also require Coenzyme-A. Large amounts of B5 are stored in the adrenal glands. Stress can deplete the body of B5. B5 may be useful in treating adrenal insufficiency, which may be associated with PCOS. B5 is a popular treatment discussed in acne forums, and the alt.skincare.acne newsgroup. It's efficacy and safety has been hotly debated over the last couple years. Some are very enthusiastic about it. Others are wary of it safety based on the fact that there are no multi-year long studies at these doses. There are only a couple studies, lasting less than a year that were not very in-depth. From antidotal evidence in acne forums, people responded to different doses, and the few studies also suggest this. For example, if acne has cleared at 2gm, then one may be able to take even less. If acne does not clear at 2gm, one may need more. After awhile at a dose that works, a lower maintenance dose may be possible, so one could try a lower dose again after some time. Calcium Pantothenate is not pure Pantothenic Acid. It is Calcium and Pantothenic Acid. Calcium Pantothenate contains 8.5% Calcium and 92% Pantothenic Acid. For each 1mg of Pantothenic Acid from Calcium Pantothenate there is 0.093mg of calcium. References: |
Pantethine: Pantethine is described as the active form of Pantothenic Acid (Vitamin B5). The body creates Pantethine from Pantothenic Acid. Pantethine is necessary for the metabolism of carbohydrates, proteins, and most importantly, fats. Several studies have shown that Pantethine can significantly lower levels of both cholesterol and triglycerides at doses of 600-1200mg. Though there are no studies directly showing increased insulin sensitivity from Pantethine, there are studies showing that when blood lipids level improve, it results in higher insulin sensitivity. If it means anything, Atkins includes Pantethine in many of their supplement products. Pantethine, which is a more direct precursor to coenzyme-A, may share many of the same benefits of Vitamin B5, including improvement in acne and adrenal insufficiency. In fact, if the theory is correct, Pantethine should be superior to B5 for acne. However, anecdotal reports are that Pantethine is not as effective for acne as high-dose B5. That may be because no one knows what dose of Pantethine to take for acne since there are no studies on it. And, no one wants to experiement with extremently high doses of Pantethine out of safety concerns. Unfortunately, Pantethine is expensive. |
Vitamin B12 : (Methylcobalamin) Folic Acid: (Folate) Vitamin B6: Several studies show elevated homocysteine in PCOS. B12, Folic Acid and B6 all work to lower Homocysteine. Metformin further increases homocysteine and is shown to lower B12 and Folic Acid. Methylcobalamin may be superior to other forms of b12 because it more readily gets to the brain. But, any form should be fine. Homocysteine is neurotoxic and accumulates in several neurological disorders. B12, B6 and especially folic acid have all been shown to help treat neurological disorders, including depression. A study shows that oral contraceptives can lower B6, and that lower B6 can contribute to depression. |
Acetyl-L-Carnitine: Many studies show increased insulin sensitivity. It can increase energy and fat loss, and lower TNF-alpha. It may be useful in depression and improving cognitive performance. Diabetics are often deficient in Carnitine, so it's likely lowered in PCOS as well. It is often recommended to take amino acids on an empty stomach so they will not compete for absorption with other protein. An animal study shows that Acetyl-L-Carnitine increased ROS (Reactive Oxygen Species) production in older animals. Lipoic Acid was shown to prevent the increased oxidative stress caused by Acetyl-L-Carnitine. |
Resveratrol: Many studies show Resveratrol lowers TNF-alpha and suppresses MMP-2 and MMP-9. It is an excellent antioxidant. |
Curcumin: This is a potent anti-inflammatory. It reduces TNF-alpha, and down regulates MMP-9 and MMP-2. It has anticancer effects. It is an excellent antioxidant. Perhaps its biggest drawback is that it is very poorly absorbed. Taking it with piperine has been shown to dramatically improve absorption, and then a lower dose could be used. |
Vitamin K: Vitamin K has been shown to be improve glucose tolerance, but the evidence is scant. Vitamin K is sometimes recommended to take with calcium and vitamin D for osteoporosis, and to keep calcium in the bones and not in blood vessels. Low vitamin K intake has been shown to induce a poor early insulin response, and late hyperinsulinemia. Doses range from 100mcg to 10mg. There does not seem to be consensus on what the best dose is. The average diet gets between 300 and 500mcg per day. |
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Vanadium: (Bis-Glycinato Oxovanadium Complex, BGOV, Vanadyl Sulfate) Vanadyl Sulfate is a more common and available form of Vanadium than BGOV. There appears to be no safe and effective dose of Vanadyl Sulfate. Doses shown in studies to be effective for insulin resistance and glucose tolerance are all 100mg or more. Yet, there is concern that 10mg may cause kidney toxicity. I could not find dose information for BGOV, but it is thought to be less toxic. At any rate, Vanadium supplements may not be very effective in patients with PCOS who are not yet diabetic. In one study, oral vanadyl sulfate improved insulin sensitivity in NIDDM but not in obese non-diabetic subjects. |
Glucosol: (banaba leaf, colosolic acid, corosolic acid, 2alpha-hydroxyursolic
acid, Lagerstroemia speciosa, Crataegus pinnatifida) Studies show improved insulin sensitivity and improved glucose transport, others show conflicting results. Pdrhealth.com notes "There are a few reports that colosolic acid lowers blood glucose levels in type 2 diabetic subjects. However, none of these reports has appeared in peer-reviewed scientific literature. ... Currently, there is no credible evidence to support any claim for the use of this substance in humans." Pdrhealth is sometimes a bit behind though. It may be good, but more studies are needed. |
L-Arginine: Several studies show increased insulin sensitivity and other improvements in diabetic conditions. In some cases it may decrease TNF-alpha. Arginine is a precursor to nitric oxide. PCOS is associated with decreased nitric oxide production. Nitric oxide is a chemical messenger used in many reactions in the body. Some believe that having extra nitric oxide available for your body to make when it needs it can have a positive impact on many conditions. It's often recommended to take amino acids on an empty stomach so they will not compete for absorption with other protein. This may be more useful for someone with high blood sugar. Hyperglycemia depletes SOD and nitric oxide and arginine. Supplementing arginine has been shown to reverse the inhibition of high glucose on nitric oxide production. |
B-Complex: It's often recommended to supplement the entire B-complex when supplementing any individual B vitamins. Most of the B vitamins may be useful in treating depression. |
Astaxanthin: Astaxanthin is a carotenoid with strong antioxidant activity. It has also been shown to have strong antiinflammatory activity and to inhibit TNF-alpha and suppress I-kappa B kinase activity. It was shown to lower LDL and raise HDL cholesterol. It may also be neuroprotective. There is some evidence that it may have anticancer activity. |
Vitamin E : (Gamma E, Gamma-Tocopherol) Vitamin E, especially Gamma E, has been shown to improve glycemic control, reduce TNF-alpha, decrease PAI-1, and reduce C-Reactive Protein. Vitamin E deficiency can increase MMP-2 and MMP-9 activity. It is a very good antioxidant. In one study Vitamin E was shown to protect hypothalamic beta-endorphin neurons from estradiol neurotoxicity, which may be an issue in PCOS. |
Probiotics: A couple studies suggest there may be some blood glucose lowering effect. One study suggests they may benefit fatty liver disease and lower TNF-alpha. Another suggests that probiotics may promote leanness. Yogurt has probiotics and there are some studies on weight loss and yogurt. Quote: "We also speculate that changes in microbial ecology prompted by Western diets, and or differences in microbial ecology between individuals living in these societies, may function as an 'environmental' factor that affects predisposition toward energy storage and obesity." Reference: Backhed F, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15718-23. Epub 2004 Oct 25. Quote: "...obesity affects the diversity of the gut microbiota and suggest that intentional manipulation of community structure may be useful for regulating energy balance in obese individuals." Reference: Ley RE, et al. Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11070-5. Epub 2005 Jul 20. Quote: "Oral administration of [Lactobacillus johnsonii] for 2 weeks also reduced the elevation of blood glucose and glucagon levels after an oral glucose load in streptozotocin-diabetic rats." Reference: Yamano T, et al. Effects of the probiotic strain Lactobacillus johnsonii
strain La1 on autonomic nerves and blood glucose in rats. Life Sci. 2006 Oct
12;79(20):1963-7. Epub 2006 Jun 29. |
Niacin: (Nicotinamide, Vitamin B3) Nicotinamide is a no-flush form of the B vitamin Niacin. The other form of Niacin is Nicotinic Acid. Nicotinamide may have benefits for PCOS distinct from Nicotinic Acid. Nicotinamide has been demonstrated, in one study, to affect glucose tolerance and slowing down diabetes progression. However, these benefits may only apply to type-1 diabetes. Among other benefits, Nicotinamide has been shown to have antioxidant activity. Nicotinamide has demonstrated a number of anti-inflammatory activities. Nicotinamide has been shown to inhibit TNF-alpha. Nicotinamide may have a calming effect and help with anxiety. In one study, high doses of Niacin (1gm or more) were shown to increase Homocysteine. |
Calcium Pyruvate: Calcium Pyruvate has some evidence of increased insulin sensitivity, fat loss, and lipid lowering effects. It may also have a positive effect on mood. The evidence is not strong for any of its reported effects. Some human studies show no effect. In studies that did show an effect on weight, the results were not impressive. Doses used were bulky: 6-44gm Pyruvate (that's just Pyruvate, not Calcium Pyruvate). 6gm Pyruvate was shown to be somewhat effective when combined with exercise. In powder form, this dose costs as little as $10/month. This can cause gas, bloating, and other intestinal distress. References: |
Vitamin C: There is minimal evidence that it can increase insulin sensitivity by reducing oxidative stress. Low levels of vitamin C and produce depression. OCPs can deplete vitamin C. Low Vitamin C can raise PAI-1, and high doses were shown to lower it. |
Garlic Extract: Several studies show antidiabetic, blood sugar lowering, and antioxidant effects. It may partly work by increasing insulin secretion. So, if you don't have high blood sugar, this may or may not have as much benefit. |
American Ginseng: Several studies show improved insulin sensitivity, glucose disposal, and weight loss. Apparently American Ginseng (Panax quinquefolius) is more effective for hyperglycemia than the Asian varieties. Ginseng may also have an unwanted estrogenic effect. |
Zinc: There is some evidence of increased insulin sensitivity, and lowered TNF-alpha. There is minimal evidence that these benefits are seen with zinc supplementation even in those who are not zinc deficient. High doses of 50mg or more were shown to elevate HbA1c levels, which is a sign of worsening diabetic symptoms. High intakes of zinc will decrease copper absorption. |
Selenium: (L-Se-Methylselenocysteine) L-Se-Methylselenocysteine is probably the best form of Selenium to take, but any common form should be fine. Several studies show increased insulin sensitivity, and lowered TNF-alpha and C-Reactive Protein. Selenium may act as an insulin mimic, but the evidence is weak. |
TMG: (Trimethylglycine, Betaine) This has been shown to reduce Homocysteine, treat depression by raising SAMe levels, and to treat and prevent nonalcoholic fatty liver disease. Insulin resistance and obesity are major risk factors for the development of nonalcoholic fatty liver disease, so it may be more common in PCOS. Doses in most studies range from 6-20gm. However, doses between 1.5-3gm have also been shown to have an effect. TMG is produced by the body. It is present in many foods but not in high amounts. References: There is a new study on fatty liver disease and PCOS: Reference: Setji TL, et al. Nonalcoholic steatohepatitis and nonalcoholic Fatty liver disease in young women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006 May;91(5):1741-7. Epub 2006 Feb 21. |
Tocotrienols: Tocotrienols have been shown to improve glycemic control and reduce TNF-alpha. They are excellent antioxidants. |
Coenzyme Q10: This has been shown to improve insulin resistance. However, there are several other studies showing no benefit, and one showing negative results. |
Gymnema Sylvestre: (gymnemic acid) This is shown to benefit diabetics who are not making enough insulin by causing increased insulin secretion. Studies show it does not improve insulin resistance. It has been shown not to cause hypoglycemia. So, it should not increase insulin secretion in those who do not have high blood sugar, and it should not contribute to hyperinsulinemia. This implies it will not be of any value if you don't have high blood sugar. |
Quercetin: This has anti-inflammatory and antioxidant effects. It reduces TNF-alpha, and inhibits MMP-9. It has benefits in some diabetic conditions. |
Manganese: This has shown benefits in some diabetic conditions in combination with other agents. |
Potassium: A Potassium deficient diet can lead to insulin resistance. Low potassium is also implicated in depression. If you are taking Spironolactone, you need to be careful with your Potassium intake. Excessive potassium intake may cause hyperkalemia in patients receiving Spironolactone. |
Avoid |
CLA: (Conjuated Linoleic Acid) This has conflicting evidence. Animal studies are encouraging, but some human studies are negative. References: (negative) Quote: "Overall, CLA appears to produce loss of fat mass and increase lean tissue mass in rodents, but the results from 13 randomized, controlled short term (<6 months) trials in humans revealed only little evidence to support that CLA reduces body weight or promotes repartitioning of body fat into fat free mass in man. However, from mice and human studies there is increasing evidence that the CLA isomer t10,c12 may produce liver hypertrophy and insulin resistance via a redistribution of fat deposition that resembles lipodystrophy." Effects of two conjugated linoleic Acid isomers on body fat mass in overweight humans. Obes Res. 2004 Apr;12(4):591-8. Quote: "A daily consumption of a drinkable dairy product containing up to 3 g of CLA isomers for 18 weeks had no statistically significant effect on body composition in overweight, middle-aged men and women." A study out in June 2004 suggests it is beneficial for weight loss after 1 year. Reference: (positive) |
Bitter Melon: (Momordica charantia) This has been described as being "structurally similar to animal insulin". Too high of a dose can cause hypoglycemia, which is further evidence that it acts just like insulin. The problem is, if it's too much like insulin, then it may contribute to insulin resistance and raise testosterone in PCOS. An insulin mimic can be a good thing if it only increases glucose uptake without any of the negative effects of insulin. This may be beneficial if you have high blood sugar. |
Trans-Fats: Trans-fats are especially bad -- worse even than saturated fats as far as their impact on diabetes. Trans-fats have evidence of decreasing HDL and generally increasing diabetes risk. Margarine is a major source of trans fatty acids. Reducing trans fats has been show to reduce the risk of developing diabetes. |
Saturated Fats: If not offset by adequate monounsaturated fats, saturated fat can be toxic to your pancreas by forming cerimide which kills pancreatic beta cells. |
Fructose: (and high fructose corn syrup) This is found in many junk foods. It may be worse than other sugars because it has been shown to raise triglycerides. |
High glycemic carbs: High glycemic carbs, like white bread, pasta, etc., can be just as bad, or worse, than refined sugar as far as its effect on insulin response and blood sugar. |
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Licorice: It may do some good things. There are at least two (supposedly there is a third somewhere) studies showing lowered androgens and improved menstrual regularity and ovulation. The problem is, it can dangerously raise blood pressure. It can lower potassium to life threatening levels, and cause fluid retention. If you plan to take this, you might want to have doctor supervision. Note that Licorice candy sold in the US does not have real licorice root in it unless it says so, and then it may have been deglycyrrhizinated, which may make it ineffective for PCOS applications. So, you need to make sure you are taking an effective form. If Licorice works by virtue of it being an antiandrogen, you may be better off using a prescription antiandrogen. Small doses are probably okay, but also probably not effective for PCOS. Higher doses which may be effective, appear dangerous. References: |
Coffee Berry: (CoffeeBerry, Caffeic Acid, Chlorogenic Acid) Coffee, and the coffee fruit it's made from, contains caffeic acid and chlorogenic acid. Chlorogenic acid was shown to inhibit glucose-6-phosphate translocase 1, which is involved in intestinal glucose transport, and may slow glucose absorption, which reduces the insulin response. However, some studies on whole coffee show a negative impact on insulin sensitivity. Caffeic acid was shown to lower blood glucose by raising insulin, which is not what you want to do in PCOS unless perhaps if you have high blood sugar. References: Johnston KL, et al. Coffee acutely modifies gastrointestinal hormone secretion and
glucose tolerance in humans: glycemic effects of chlorogenic acid and caffeine. Am
J Clin Nutr. 2003 Oct;78(4):728-33. |
Example Supplement Regimen #1 |
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Disclaimer: This example is not to be taken as advice. Consult your doctor before using any treatments. Dosages or pill counts below may be inaccurate. In choosing supplement products in this example regimen, I sought to include: NAC The supplements above appear to have the strongest evidence for treating PCOS, given my biased objectives. If they were easy enough to add without too much trouble or expense, I attempted to include: High-dose Biotin This example regimen includes the following seven products:
Purchasing these products from somewhere like iherb.com costs about $72 per month. If you know of a cheaper source, The combination provides the following totals per day:
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Example Supplement Regimen #2 (Powder) |
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Disclaimer: This example is not to be taken as advice. Consult your doctor before using any treatments. Dosages or pill counts below may be inaccurate. In this example we will be using supplements in powder form, where possible. Some people would consider this choice pretty extreme. However, anyone who has baked cookies and measured flour and sugar, can make a custom powder vitamin supplement. Using supplements in powder form has several advantages. First, it allows for exact dosing. You can adjust the amount of each powder to get the exact number of milligrams you want. Second, it allows you to more easily choose the form of each supplement you want to take. Third, it's faster to take vitamins in powder form. With pills, you have to open each container, remember how many you are supposed to take for that time of day, count out the number of pills, and swallow each one with plenty of liquid. If you have 15 pills to take, that takes several minutes and requires thought which can lead to mistakes ("Did I take 2 this morning, or only one?"). With a powder, you have one container to open, take one scoop (assuming you made a pre-measured scooper) and throw it into juice or other beverage, stir and drink it -- there is no swallowing of pills, no counting, and it only takes a matter of seconds. You can pre-mix several months worth at a time. Finally, buying bulk powders tends to be cheaper than buying pills. Somewhere, pills started out as powders. When you buy pills, you are paying the manufacturer to turn the powder into pills. When buying powders, you can avoid having to pay that cost. A disadvantage to powders is that you have to mix them beforehand. It would be easy to make a mistake when combining the powders and end up taking the wrong dose. You need to know what you are doing, and you have to get the numbers right. Powders are difficult to measure accurately because some can be packed down and it can be impossible to judge if you have measured correctly. To avoid this problem, you can use a highly accurate digital scale, but using a scale is tedious. It takes time to organize and measure each ingredient. It takes time to plan and calculate how much needs to go into a batch and the volume of a single serving. Some powders do not dissolve completely in water and you are left with stuff floating in your drink. Finally, some powders are tasteless, but others can taste pretty awful or are too alkali, or acidic and can burn your throat. Some things are much better to take in a capsule. This example includes the following products: Powders (3 servings per day):
Pills:
B-A-C is my abbreviation for beyond-a-century.com. Beyond-a-century sells many supplements in powder form at cheap prices. The other products are often cheaper elsewhere. From these sources, this regimen costs about $72 per month, which is the same price as Regimen #1. If you know of a cheaper source, The combination provides the following totals per day:
For the same price, this Regimen has several advantages over Regimen #1: Only 14 pills per day, compared to 21 pills in Regimen #1 |
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Copyright © 2006 Mary Kate Roget
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