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Unread 05-21-2008, 07:02 PM
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Question d-chiro-inositol or d-pinitol supplementation when reintroducing carbs?

Lyle, in The Ketogenic Diet you mention a couple of times that, after starvation, fasting, or ketogenic dieting (including PSMF), people will experience some symptoms of insulin resistance as they begin to reintroduce carbs into their diet. This is because certain enzymes that play a part in carb metabolism have been downregulated, & take a bit of time to "wake up" again after eating carbs again (5 hours in the liver, 24-48 hours in muscles).

I'm wondering if you know of any studies or even just anecdotes of people coming off fasts or low-carb diets who might have supplemented with d-chiro-inositol (DCI) or d-pinitol (both forms of the B-vitamin inositol) to offset this problem? Apparently DCI is one of the substances that gets downregulated with fasts (see fourth study listed below). Turns out that DCI is already deficient in insulin resistant people.

It at least seems worth a try. Here are the details I gathered yesterday/last night.

Yesterday on an email list someone mentioned d-chiro-inositol (DCI) (part of the B-vitamin group), which I'd never heard of before, but which plays a part in carbohydrate metabolism as some sort of helper to insulin. It turns out insulin resistant/Type 2 diabetic people in general, & women with polycystic ovarian syndrome (PCOS) in particular (which affects about 10% of all women, including me), have been found to have deficient levels of DCI in their bodies.

It's theorized that this is due to an impairment in whatever it takes for the closely related myo-inositol to be changed into d-chiro-inositol in the body. Furthermore, studies have shown that women with PCOS & Type 2 diabetics who are given supplements of DCI have improvements in insulin sensitivity, blood sugar levels, blood insulin levels, etc. -- as well as improvement of the additional symptoms (high androgen levels, irregular to nonexistent menstrual periods, infertility) that tend to accompany PCOS. On an anecdotal level, there are a number of women at the forums at Soulcysters.com (a major PCOS support site) who report having successfully regulated their menstrual cycles & achieving pregnancy (as well as other improvements) through supplementation with DCI. The word "miracle" tends to show up. (Well, I guess miracles do happen when deficiencies are addressed. That's how sailors must've felt when they learned all they had to keep from getting scurvy was to eat citrus fruits.)

Here's some relevant studies. All of these have full-text available online:
Unfortunately there are few sources of DCI supplements, & they tend to be expensive (e.g., Chiral Balance). Apparently the mega-pharmaceutical companies haven't found it worth their while to bring their own versions to market. Less expensive supplements called simply inositol or myo-inositol seem to be helpful for some people, but since the problem insulin resistant people seem to have is in changing myo-inositol to DCI, it's really DCI that needs to be supplemented. Another supplement that might work, though, is d-pinitol (aka D-chiro (+)-o-methyl inositol), which is available under the trade name Inizitol (New Zealand company, but there are distributors in the U.S. & Canada); this is also recommended as a possible supplement for PCOS by Richard Bernstein in Dr. Bernstein's Diabetes Solution. Apparently d-pinitol is also used a lot by athletes and affects whole-body creatine retention. More info on d-pinitol & DCI from a PCOS-suppement supplier here.

The food source with the highest level of DCI is buckwheat (which is actually a rhubarb relative, not a grain), especially in buckwheat bran (farinetta) (available in quantity from Minndak.com). Apparently some other legumes (e.g., garbanzo beans) also contain small quantities of DCI. People at Soulcysters, who have become quite expert at creating recipes containing these foods, have also mentioned carob syrup & soy lecithin -- I think those are supposed to be sources of pinitol. Carob syrup is something of a problem since it's got a lot of sugar.

... Since I'm insulin resistant & have PCOS, I probably have this deficiency in d-chiro-inositol, so I am likely going to get some of this stuff no matter how expensive & experiment with it when I get back from my trip.

-- Mel
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Progress log (RFL cat. 3) Blog
5-1/4" (160 cm), 55, female, insulin resistant
Restart 17 Mar 2014: start 198.2 (89.9 kg) > current 180.8 (82.0 kg) (post-diet break) > goal 140 (63.6 kg)

Last edited by yksin : 05-21-2008 at 07:06 PM. Reason: typo
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Unread 05-22-2008, 10:07 AM
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arguably the primary effector for the fasting issue is PDH downregulation

has anybody shown that this stuff will work orally?
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Unread 05-22-2008, 04:59 PM
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Quote:
Originally Posted by lylemcd View Post
arguably the primary effector for the fasting issue is PDH downregulation
Okay, thanks, I'll look at that.

Quote:
has anybody shown that this stuff will work orally?
Yes, at least in PCOS, Type 2 diabetes, & general insulin resistance, both in human studies & anecdotally. Anecdotally, d-pinitol (Inzitol) is getting some attention in athletic/bodybuilder circles.

d-chiro-inositol

One of the central studies seems to be one in the New England Journal of Medicine (Nester, et al. Ovulatory and metabolic effects of d-chiro-inositol in the polycystic ovary syndrome. New England Journal of Medicine 340 (1999): 1314-1320). They used 1200 mg. oral doses of D-chiro-inositol in the form of a product-in-development called INS-1 from Insmed Pharmaceuticals. 22 women with PCOS were matched against a placebo group of 22 women also with PCOS. Conclusions: "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 research: Insmed was developing INS-2 for use in PCOS, diabetes, & dyslipidemia (high blood lipids) & ran Phase II clinical trials in 2001-2002. But they discontinued development of INS-2 in Sept. 2002, saying that "INS-1 was safe and well tolerated but did not achieve statistical significance on its primary efficacy measures" -- in spite of earlier press releases about the same trials that said there were statistically significant improvements (in Type 2 diabetes; in obese women w/ PCOS & nondiabetics with dyslipidemia). Anecdotally, women on the Soulcysters PCOS board reported participating in the clinical trials & experiencing big improvements on INS-1 -- for example, regular periods (which sometimes go by the slang term "AF" meaning "Aunt Flo") & ovulation, lower hirsutism, better skin, no more hypoglycemia -- that went away after the trials ended & they were no longer getting the INS-1. People have also reported better weight loss. All of which makes me think that Insmed's decision to discontinue was premature. Sure was from the PCOS-sufferers POV. (I'm not trying to get preggers myself, but a lot of women with PCOS are, & inability to have periods or to ovulate creates a problem.)

Anecdotally, women at Soulcysters eating food sources of d-chiro-inositol such as "PCOS-blaster" muffins containing buckwheat bran brings improvements, & so do the oral DCI supplements from the company Chiral Balance. Chiral Balance is a small company run, I gather, by a couple of biochemists who seem to be approaching DCI supplementation from a nutritional supplement rather than drug/pharmaceutical angle. Unfortunately, it's still expensive, & nutritional supplements aren't usually covered by health insurance.

Other studies in humans with related to DCI -- Iuorno et al. 2002 (DCI supplementation in PCOS);
Baillargeon et al. 2004
(metformin for PCOS seems to increase DCI-containing inositolphosphoglycan). There still seems to be a lot of study of DCI's mechanisms in insulin metabolism in mice & other animals too.

D-pinitol

An alternative oral supplement is d-pinitol (3-O-methyl-chiroinositol) -- which it seems d-chiro-inositol can easily be made from, possibly even in insulin resistant people. (I'm still trying to understand the science -- I'm smart enough I guess, but not a biochemist.) Pinitol is found in high concentrations in some legumes (such as soy), plants, fruits, and parts of pine trees like the sugar pine. Two manufactured supplements containing: Inzitol & ViTAL Nutrients d-Pinitol 600. (About $120 per 60-cap bottle on Amazon -- just about as expensive as Chiral Balance's DCI. But $79.95/bottle at this point from this source.)

Inzitol is found in a product called Meta-Cel, which also contained creatine & is aimed at bodybuilders. Also apparently in another bodybuilder supplement called Nitro-Tech that makes all kinds of claims. Also apparently in some products from PVL Nutrients, but it's not readily apparent which ones. A Google search on Inzitol brings up a lot of hits about the use of Inzitol in athletics, including bodybuilding, where it's alleged to help with creatine utilization. E.g., this interview with someone at the New Zealand company that makes Inzitol.

In one human study on pinitol I found in PubMed, pinitol was found to increase levels of d-chiro-inositol in the body (14-fold increase in DCI levels with 20 mg pinitol per kg of body weight per day for four weeks in diabetic patients), but not to improve insulin sensitivity (Davis et al. 2000). Another found it didn't help insulin sensitivity in nondiabetic older people (Campbell et al. 2004). On the other hand, Kim et al. 2007 in a study of poorly controlled Type 2 diabetics, found "fasting glucose, post-prandial glucose levels, and hemoglobin A1c were significantly decreased." Similarly, Kang et al. 2006. (Both these latter two studies uses pinitol from soy sources, not sure what the other studies used. I believe Inzitol is manufactured from pine tree sources.)

Mechanism

From the best I understand, the proven low levels of d-chiro-inositol in Type 2 diabetics & women w/ PCOS (& other insulin resistant people) appears to be a deficiency caused by an inability to transform myo-inositol into d-chiro-inositol within the body. Whether that's from some sort of genetic problem or due to environment (hyperglycemia &/or hyperinsulinemia, perhaps) isn't clear. But I'm thinking it's quite similar to how we as human beings are supposed to be able to change the omega-3 DHA found in flax seed into the essential omega-3s EPA & DHA. But, we're pretty inefficient at it, & many people can't seem to do it at all, so therefore we eat fish oil in order to get enough EPA/DHA. Most people can make DCI in their own bodies, but insulin resistant people's bodies are lousy at it; so we need supplementation.

So... this might not have that much utility as I thought it might for insulin sensitive ketogenic/PSMF dieters, who probably don't have this deficiency... but for those of us who are insulin resistant.... The bodybuilder supplement industry seems to be embracing Inzitol, anyway. At any rate, for anyone who wants to experiment, seems that both DCI & pinitol are different from metformin (glucophage) as insulin-sensitizers in that they are naturally found in the human body, & all reports seem to be that oral supplementation is well-tolerated & doesn't give the nasty side effects metformin often does.

According to Joseph Larner, who's been studying d-chiro-inositol for a couple of decades, DCI was "originally discovered as a component of a putative mediator of intracellular insulin action, where as a putative mediator, it accelerates the dephosphorylation of glycogen synthase and pyruvate dehydrogenase, rate limiting enzymes of non-oxidative and oxidative glucose disposal." Further explained, most of it understandable even to non-biochemist-me, in the journal article of his I posted yesterday, D-chiro-inositol – its functional role in insulin action and its deficit in insulin resistance. International Journal of Experimental Diabetes Research 3(1) (2002): 47-60.

-- Mel
__________________
Progress log (RFL cat. 3) Blog
5-1/4" (160 cm), 55, female, insulin resistant
Restart 17 Mar 2014: start 198.2 (89.9 kg) > current 180.8 (82.0 kg) (post-diet break) > goal 140 (63.6 kg)

Last edited by yksin : 05-22-2008 at 05:07 PM. Reason: typo
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