Inositol, Choline and Insulin Resistance

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.

Magnesium

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.

Inositol (About)

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 [4]. 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].

Article’s references:

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

The following is from Online Holistic Health’s article: “Vitamin B-8: Inositol” (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 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.”

Regarding inositol:

NOTE: When not designated as myo- (MI) nor chiro-inositol (DCI), myo-inositol is usually meant.

Inositol is vital for (1a):

    • 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.

Other roles of inositol (from reference 1a, if not noted otherwise):

  1. Inositol increases the effectiveness of Vitamin E, an important anti-oxidant.
  2. It 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.
  3. 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 online Holistic Health article (1a) 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.”
  4. 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).
  5. Inositol also plays a role in the amount of fat stored in the liver; too much of that fat is known as Fatty Liver Disease. For lots of great information about this disease, see the Liver Cleansing Diet article (15). See also my notes in the “About Fatty Liver Disease” section, below (I will eventually move it to a separate article).

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.

  1. Choline is  important for the brain and other neurologic tissue. From a Mercola article (12; see his article for his references 7, 8 and 9): “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, other scholars outlined data to support the hypothesis that cholinergic dysfunction contributes to Alzheimer’s.

By 2008, 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. 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.”

About Fatty Liver Disease:

Consider moving the following personal text to separate article.

There are two forms: AFLD (alcoholic fatty liver disease) and  NAFLD (non-alcoholic fatty liver disease). If your doc says you have fatty liver disease, he will ask how many alcohol beverages you drink: if 2 or less, it is NAFLD; if more than 2, it is AFLD, but NAFLD’s relationship with insulin resistance may also play a role. 

My discoveries and experience with NAFLD

When I was first diagnosed with insulin resistance, I was also diagnosed with NAFLD, but the myo-inositol link between these two diseases was not yet known. In 2015, I started a ketogenic eating plan which greatly improved my health (by no longer craving sugar/starch), but I didn’t lose any weight, despite my body’s use of fat for fuel (ketosis).

In 2018, I started taking a low-dose (¼ tsp/day) of Pure Encapsulations brand of myo-inositol powder* for my insulin resistance (as recommended by my naturopath). I was 70 pounds overweight before I started the inositol. After I started the inositol, I lost 30 pounds in 2½ months (about 0.4 lb/day, average). But even tho I continued to take the inositol and followed my keto eating plan, I did not lose any more weight. Now, in 2020, it occurred to me that my NAFLD might be playing a role in my inability to lose more weight.

‘* Recommended (cited) dose of myo-inositol:

Compare 2 different brands, per info on product label:

  1. Pure Encapsulations brand, see Amazon ASIN B002HZ5MRM for photo of the label:
    • 2 scoops or 2 tsp, 1 – 2 times daily.
    • each scoop (1 tsp) provides 2.1 g of myo-inositol.
    • my current daily dose of ¼ tsp provides 525 mg.
    • 1 jar provides 120 1-scoop (1 tsp) servings, or 480 servings of ¼ tsp each, for cost of $41 per jar or $0.09 per ¼ tsp serving. (total of 252 g per jar)
    • This is the brand recommended by my naturopath
  2. For comparison: Lake Ave Nutrition brand, see iherb code LKN-01669 for photo of label:
    • ¼ tsp provides 730 mg of myo-inositol (total of 43.8 g/jar)
    • 1 jar provides 60 servings of ¼ tsp each, for cost of $16 per jar, or $0.27 per ¼ tsp serving; however, each ¼ tsp serving provides 1.4 times more inositol than Pure Encapsulations (730/525=1.4)…. If you use this brand, you will need less than ¼ tsp/day. Best to measure by mg on a scale, rather than by volume in a teaspoon.

See the following articles for more:

    • Nexus News Feed article: Fight the Effects of Fatty Liver with Myo-inositol (13) for more about “fighting the effects of fatty liver with myo-inositol”
    • Fitness Edge article: Inositol and Weight Loss (14).
    • Liver Cleansing Diet article: Fatty Liver Causes: AFLD and NAFLD, In-depth (15)
    • livercleansing-diet.org/fatty-liver-causes/

What I can do next

2020: First, I must note that I currently eat a good-quality diet, by eating locally grown/produced Organic plant foods and locally-raised, pasture-fed animal ingredients whenever possible. I avoid processed foods that contain GMOs, oxidized fats, sugar, starch, etc.

My diet includes meats, eggs, milk/cream/butter, nuts, fruits, veggies, and small amounts of whole grain foods (preferably sprouted or sourdough). I use real olive oil and coconut oil for cooking; I follow a cyclic-keto diet plan (as recommended by Dr. Mercola: 4 days of keto and 3 days with more carbs/less fat each week). See Diet for Health, Part 2: Cat’s diet summary for more.

I’ve continued to take the low-dose of myo-inositol so that I don’t start to regain that 30 pounds, and perhaps will begin to lose weight again.  Now that I’m considering NAFLD as a possible influence in my lack of weight/fat loss, I will gradually increase my dose to that recommended on the Pure Encapsulations container (see above), which is 4 – 8 times my current dosage); I hope to see some progress. Here’s my increase plan:

    • Start with increasing to ½ tsp daily (divided between 2 doses, one in AM and one in evening), for about 2- weeks; then
    • Increase to ¾ tsp daily divided between 2 doses, for 2 weeks; then
    • Increase to 1 tsp daily, divided between 2 doses, for 2 – 4 weeks.
    • If that doesn’t start the reduction in liver fat, I’ll continue the slowly increase until I’m taking full dose of 2 tsp daily, divided between 2 or 3 doses..

But I also need to detox my liver. I’ve been taking an herbal tincture for detoxing and supporting the liver (contains dandelion and burdock roots and milk thistle seed); I can also do a 5-day Veggie Juice Fast (that I learned at the Wellness Education Center), or at least add a bottle of their veggie juices to my daily eating plan.

need more

some articles to check out:

References

  1. Online Holisitic Health
    1. onlineholistichealth.com/vitamins-2/vitamin-b8-inositol.html
    2. onlineholistichealth.com/inositol-deficiency-linked-to-depression/
    3. onlineholistichealth.com/choline-too-crucial-to-ignore/ (about non-alcoholic fatty liver disease (NAFLD) being reversed by addition of choline to the diet)
  2. Theralogix: How Inositol benefits 6 health conditions,
  3. Restart Med: How to Use Inositol for Weight Loss
  4. (moved to 8G)
  5. Online Holistic Health:
    1. onlineholistichealth.com/choline-too-crucial-to-ignore/
    2. onlineholistichealth.com/inositol-deficiency-linked-to-depression/
  6. optimallivingdynamics.com/blog/the-little-known-nutrient-that-can-help-treat-anxiety-and-depression-ocd-inositol
  7. onlineholistichealth.com/inositol-deficiency-linked-to-depression/
  8. ncbi abstracts:
    1. ncbi.nlm.nih.gov/pubmed/7622343
    2. ncbi.nlm.nih.gov/pubmed/6278902
    3. ncbi.nlm.nih.gov/pubmed/22986984
    4. ncbi.nlm.nih.gov/pubmed/9169302
    5. ncbi.nlm.nih.gov/pubmed/3017301
    6. ncbi.nlm.nih.gov/pubmed/8131066
    7. (4) ncbi.nlm.nih.gov/pmc/articles/PMC2972396/ (2010 research abstract on D-chiro-inositol as a secondary messenger to insulin)
  9.  westsidebehavioralcare.com/article/inositol-and-the-treatment-of-obsessive-compulsive-disorder-ocd/
  10. glytech-inc.com/glycan/what-are-glycans/
  11. hindawi.com/journals/ije/2016/8720342/
  12. Mercola: articles.mercola.com/sites/articles/archive/2020/05/25/choline-missing-link-in-preventing-dementia.aspx
  13. nexusnewsfeed.com/article/climate-ecology/fight-the-effects-of-fatty-liver-with-myo-inositol/
  14. fitnessedge.net/inositol-and-weight-loss/
  15. livercleansing-diet.org/fatty-liver-causes/

About Cat

See my 'About' page
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