By Cat, May 2019
Insulin resistance is a metabolic disorder that is the precursor to Type-2 Diabetes. It means that the insulin receptors on cell walls no longer respond to insulin, starving the cells of glucose for fuel. This typically starts as hypoglycemia (low blood sugar), but eventually leads to weight gain and hyperglycemia (high blood-sugar, or Type-2 Diabetes), if not resolved at the cellular level.
For me, I first noticed the symptoms of hypoglycemia such as crankiness, light-headedness, impatience, and shaky hands when I was in my early 20s. This was before medical science acknowledged that hypoglycemia was a real problem at the cellular level. My doctor said it was “all in my head.” I knew that it had something to do with my diet primarily comprised of sugar and starch, with very little protein and fat, because I was unemployed and couldn’t afford a better diet.
I wasn’t diagnosed with insulin resistance until my mid 40s, but even then, my doctors didn’t know what caused it nor how to treat it. So I started researching the literature. I learned it meant that while my cells needed fuel, they were unable to respond to insulin when it knocked on the cellular door (insulin receptors), and thus could not take-up the sugar waiting for the door to open. But what kept the receptors from doing their job? Now, in my 70s, I’m finally beginning to find answers.
- Includes: 1. Inositol (About); 2. Importance of Inositol and Choline;
- See also: 1. Choline & Lecithin; 2. Notes on Insulin Resistance (IR); 3. Magnesium (About); 4. Reversing Insulin Resistance (IR) (from old iWeb – Health-Disease section; link may no longer work)
This mineral plays a significant role in insulin resistance, as discussed in my article: Magnesium (About). It is a difficult mineral to absorb, so may of us just aren’t getting enough. Science is just beginning to understand the importance of insufficient magnesium in people with type-2 diabetes and heart disease, both of which are out of control in our modern society.
I first learned about taking inositol for my insulin resistance, from my naturopath, Dr. Steven Gordon; he suggested taking 1/16 – 1/4 tsp daily. It has had amazing benefits for me, including:
- Weight loss around my middle;
- Resolving my food sensitivity to alpha-lipoid acid and to MgCl2 supplements;
- My March 2019 blood tests for fasting insulin and glucose levels indicate some improvement; I’m no longer in the pre-diabetic category!
But I still have a ways to go. And now I’m learning about related dietary factors that will help, and I record them here (I anticipate many updates to this posting as I learn more).
There are two natural forms of inositol: Myo- and D-chiro-inositol (MI and DCI, respectively). DCI is made from MI in the body. When it comes to supporting insulin uptake and transportation, both are essential parts of separate glycans, that act as secondary messengers to insulin. (8G)
[Glycans are chain-like structures that are composed of single sugar molecules (monosaccharides) such as glucose, fructose and galactose linked together in a single-chain or branched-chain structure, and are usually found attached to proteins and lipids in living organisms. Their constituent monosaccharides, their combination and bonding position, and the type (or absence) of branching can all affect the properties and roles of these “glycoconjugates.” (10)]
- One glycan is comprised of MI, glucosamine, galactose and ethanolamine;
- The other glycan is comprised of galactosamine and DCI.
I’m still trying to learn how the role of each glycan is different. I believe the answer is in the 2010 research abstract on D-chiro-inositol as a secondary messenger to insulin (8G), but it is very technical with lots of abbreviations, so will take some serious study before I “get it.”
Another research abstract (11) states (note: the reference numbers 4, 5, and 6 are not my references but rather those of the article’s writers; I’ve copied their references below the quote) :
“DCI and MI have different physiological roles since the former is crucial for glycogen synthesis while the latter increases cellular glucose uptake . Each tissue has its own MI/DCI ratio, which is maintained through the conversion of myoinositol to D-chiro inositol occurring in tissues expressing the specific epimerase. High DCI levels are present in glycogen storage tissues, such as fat, liver, and muscle, whereas very low levels of DCI are typical of tissues with high glucose utilization, such as the brain and heart [5, 6].
4. L. C. Huang, M. C. Fonteles, D. B. Houston, C. Zhang, and J. Larner, “Chiroinositol deficiency and insulin resistance. III. Acute glycogenic and hypoglycemic effects of two inositol phosphoglycan insulin mediators in normal and streptozotocin-diabetic rats in vivo,” Endocrinology, vol. 132, no. 2, pp. 652–657, 1993.
5. A. Bevilacqua, G. Carlomagno, S. Gerli et al., “Results from the International Consensus Conference on myo-inositol and D-chiro-inositol in obstetrics and gynecology—assisted reproduction technology,” Gynecological Endocrinology, vol. 31, no. 6, pp. 441–446, 2015.
6. F. Facchinetti, M. Bizzarri, S. Benvenga et al., “Results from the international consensus conference on Myo-inositol and d-chiro-inositol in obstetrics and gynecology: the link between metabolic syndrome and PCOS,” European Journal of Obstetrics and Gynecology and Reproductive Biology, vol. 195, pp. 72–76, 2015.
Importance of Inositol and Choline
NOTE: When not designated as myo- (MI) nor chiro-inositol (DCI), myo-inositol is usually meant.
The following is from Online Holistic Health (1a). You may not be familiar with the term “phospholipids” used in the quote. These are primarily fatty acids linked to a phosphorous group, and comprise the majority of molecules in the cell membrane:
Inositol is vital for:
- Prevention of fatty build-up in the liver and heart;
- Promotes healthy hair growth;
- Aids in the metabolism of nutrients into energy;
- Vital for nerve transmissions, and an essential nutrient for the brain; and
- Increases effectiveness of Vitamin E, an important anti-oxidant.
Inositol and choline, though quite different chemically, appear to work synergistically; they are both essential components of phospholipids, the most important lipids (fats) in plants and animals. Together, inositol and choline make what’s known as lecithin. Lecithin assists in the absorption of Vitamin B1 (thiamin) and Vitamin A, indirectly making inositol and choline crucial vitamins.
It has also been observed that inositol increases the effectiveness of Vitamin E, an important anti-oxidant.
Inositol helps with nutrient transport across cell membranes and inside the cell. Like choline (Vitamin B4), inositol is a precursor of phospholipids which are the primary component of cell membranes. Nutrient transport involves receptors such as insulin receptors which make uptake of glucose by the cells from the blood possible.
Inositol also plays a key role in neurotransmission, and can also have profound effect on people with depression and depressive disorders (7). Note, the author of the article did not provide a reference for the following quote; see below for more, that include references.
“An Israeli study found that inositol is an effective treatment for depression currently being treated with serotonin-specific reuptake inhibitors (SSRI’s):
“These results suggest that inositol has therapeutic effects in the spectrum of illness responsive to serotonin selective re-uptake inhibitors, including depression, panic and OCD, [but] is not beneficial in schizophrenia, Alzheimer’s ADDH, autism or ECT-induced cognitive impairment.””
Studies show that inositol can increase GABA-A receptor function and enhance serotonin receptor sensitivity, working similarly to anti-anxiety (benzodiazepines) and antidepressant (SSRIs) medications. (8A) It can also help with OCD behavior (6,7,8B-8F,9).
Regarding choline: Among many of its advantages is its ability to reverse non-alcoholic fatty liver disease (NAFLD), which results from increase in blood glucose from insulin resistance (1C). It may also be the missing link in preventing dementia such as Alzheimer’s disease.
Choline is important for the brain and other neurologic tissue. From a Mercola article (12):
“As explained in a recently published paper, scientists analyzed the effect proton pump inhibitors have on the development of dementia. They recognized indicators pointing to cholinergic dysfunction in the development of dementia. In a review article from 1999,7 other scholars outlined data to support the hypothesis that cholinergic dysfunction contributes to Alzheimer’s.
By 2008,8 the research community had identified areas of the brain where cholinergic dysfunction may influence dementia. Subsequently, acetylcholine was recognized for the central role it plays in the nervous system.9 It requires an enzyme to synthesize from acetyl-COA and choline. That enzyme is choline acetyltransferase.
Cholinergic synapses are found throughout the brain, including the basal forebrain, which is severely damaged in those who have the disease. With further research,10 scientists found using cholinesterase inhibitors could increase acetylcholine in the brain, which has proven to be clinically useful in the treatment of Alzheimer’s dementia.”
some articles to check out:
- ncbi.nlm.nih.gov/pmc/articles/PMC3601486/ (has to do with NAFLD)
- ncbi.nlm.nih.gov/pmc/articles/PMC2478565/ (DCI and IR)
- lpi.oregonstate.edu/mic/other-nutrients/choline (especially section on Structural Integrity of Cell Membranes)
- Online Holisitic Health
- onlineholistichealth.com/choline-too-crucial-to-ignore/ (about non-alcoholic fatty liver disease (NAFLD) being reversed by addition of choline to the diet)
- Theralogix: How Inositol benefits 6 health conditions,
- Restart Med: How to Use Inositol for Weight Loss
- (moved to 8G)
- Online Holistic Health:
- ncbi abstracts:
- (4) ncbi.nlm.nih.gov/pmc/articles/PMC2972396/ (2010 research abstract on D-chiro-inositol as a secondary messenger to insulin)
- Mercola: articles.mercola.com/sites/articles/archive/2020/05/25/choline-missing-link-in-preventing-dementia.aspx