Insulin Resistance & Weight Loss Resistance.
Understanding The Role of Insulin

What is Insulin | Insulin Resistance | Supplements | Chromium Picolinate | Alpha Lipoic Acid | Inositol | Berberine HCL | Gymnema Sylvestere | Cinnamon Bark Extract | Fenugreek Seed Extract

Insulin resistance causes weight loss resistance. It is one of the commonest reasons why most people struggle with weight loss.
Each and every cell in the body is involved in metabolic and biochemical reactions that serve two major purposes - to consume energy or produce energy.
Energy-consuming processes are classified as anabolic and energy-producing processes are classified as catabolic.

Tip: Think of "Anabolic" as ENABLE (Build) and Catabolic as CUT (Consume, burn, breakdown into small pieces) :-)

Anabolic reactions utilize available energy to build cellular components and tissues.
For example, when you consume essential amino acids, your body can use them (and available energy) to synthesize new muscle tissue.
On the contrary, catabolic reactions break down substrates/molecules (like sugar) to produce energy when the body needs it to carry out essential biological processes (such as contracting muscle tissue so you can move or even things as simple as breathing).
A multitude of factors affects when and where these cellular reactions take place, such as hormones, neurotransmitters, nutrition, exercise, immune function, and much more.
So, now that we have a rudimentary understanding of what cellular metabolism entails, we are going to zero in on a fairly misunderstood and controversial peptide hormone - insulin.
Let’s dive into how insulin regulates energy storage and can ultimately impact your weight loss efforts.

What is Insulin

Insulin is a peptide hormone (meaning it’s made up of a specific sequence of amino acids) that is produced in the pancreas as needed to help clear glucose (sugar) from the bloodstream.
As such, insulin is considered a “storage hormone” because it essentially helps cells absorb and store glucose (and other substrates).
However, insulin doesn’t necessarily do this on its own, but more so it signals to other cellular molecules to move sugar out of the blood and into the cell.
Specifically, insulin upregulates the activity of glucose-transport proteins (GLUTs), which help facilitate the uptake of sugar across cell membranes so that they can be absorbed and used to produce energy (as ATP).
Moreover, insulin is a potent anabolic hormone in muscle tissue since it stimulates protein synthesis, especially when amino acids are replete.¹
Even when amino acids are limited, insulin works as an anti-catabolic hormone in muscle tissue by preventing the breakdown of muscle protein.
Naturally, insulin is a very essential hormone for us as humans since it helps us build and maintain lean body mass, but this isn’t to say that the more insulin you produce (and the more sugar you eat), the better.
Eating a carbohydrate-rich diet can lead to rapid gains in body fat if you’re not careful. Your body can only store so much glucose (as glycogen), and once you surpass that amount, the sugar in your bloodstream is more likely to be converted to fat and subsequently stored in adipocytes, especially in the liver.
This drastically increases the risk of fatty liver disease, which is a serious condition that can make losing weight a much more arduous task.²
Thus, diets higher in carbs (and sugar) are generally not ideal for weight loss, particularly if you’re not highly active.
This doesn’t necessarily mean you have to avoid carbohydrates altogether, but as with most any substance, the difference between medicine and poison is in the dose.

Insulin Resistance and Weight Loss

If you continually eat a diet rich in sugar/carbs, the pancreas will need to work harder to produce enough insulin to keep blood glucose levels in a normal range.
Eventually, this can cause cells to become resistant to the effects of insulin, leading to a condition called “insulin resistance.”
This feeds into a sort of vicious cycle where your pancreas keeps trying to produce more insulin to compensate for the high blood glucose content and impaired insulin signaling.

This consequently damages the pancreas, causing it to stop producing insulin - this condition is known as type-2 diabetes.
If dietary and lifestyle changes aren’t made at this point, chronic hyperglycemia (elevated blood glucose) can damage the vascular system and harm vital organs.
Once this happens, you’re likely to experience a myriad of debilitating symptoms, including:

1. Lethargy
2. Bloating
3. Nausea
4. Headaches
5. Dizziness
6. Lightheadedness
7. Cold sweating

Obviously, this not going to be conducive to helping you lose weight.
Moreover, type-2 diabetes and hyperglycemia are major risk factors for cardiovascular disease, stroke, myocardial infarction, peripheral neuropathy, and a host of other health conditions.³
This is different from type-1 diabetes, which is generally an inborn condition where your pancreas doesn’t produce any insulin but your cells still properly respond to insulin, meaning if you take insulin medication you can safely consume carbohydrate-rich foods (in moderation).
Hence, type-1 diabetes is sometimes referred to as insulin-dependent diabetes, whereas type-2 diabetes is non-insulin-dependent diabetes.
This all might make insulin sound like a “bad” hormone when it comes to weight loss, but the reality is that insulin - when functioning properly - is actually somewhat of a good thing for losing body fat since it helps protect lean body mass.
The promising news is that exercise, diet, and certain nutritional supplements can effectively reverse insulin resistance and restore healthy pancreas function in those with type-2 diabetes.
When the body is more insulin sensitive, you’ll be able to lose weight easier and faster (even while eating a modest amount of carbohydrates).

Supplements that Promote Insulin Sensitivity

Make no mistake that there is an immense body of research that shows there’s a strong correlation between insulin resistance and type-2 diabetes and fat gain.^4,5
In other words, it becomes much harder to lose weight when the cells are resistant to the effects of insulin and/or if your pancreas isn’t functioning as it should.
Not only that, but you’ll be more likely to gain body fat if you don’t make changes to your eating and exercise habits.
On the flip side, being highly insulin sensitive means your cells readily respond to insulin’s signals so that your blood glucose remains in a healthy range.
Essentially, if you’re insulin sensitive, your body will be more efficient at putting carbohydrates to “good use” (e.g. using them for energy) and less likely to convert them to adipose tissue.
Now, before you try using any dietary supplements to improve your insulin sensitivity, be sure that you make the necessary changes to your nutrition plan and exercise regimen.
Supplements can certainly help and work wonders for many people, but they are meant to be used in conjunction with a healthy diet and active lifestyle.
For most people who are insulin resistant/type-2 diabetic, the main thing is to keep carbohydrate and total calorie intake low.
You want to emphasize healthy fats and quality protein sources since these have minimal impact on insulin secretion and the body doesn’t need insulin to properly use these nutrients for energy.
Very-low-carb diets, like the ketogenic diet, have actually been shown to prevent diet-induced hyperglycemia and reverse type-2 diabetes without the use of medication.⁶
With that in mind, here are some of the best supplements to take for promoting insulin sensitivity and weight loss:

Chromium Picolinate

Chromium is an essential trace mineral that has many functions in the human body, serving as an electrolyte and intermediate in a variety of metabolic pathways. While chromium has been shown to promote insulin sensitivity, it’s also beneficial for helping reduce sugar cravings and improving mood by regulating the actions of serotonin and cortisol.⁷
The key is to use a supplement that features bioavailable forms of chromium, such as chromium picolinate and chromium polynicotinate.⁸ These are known as chelated forms of chromium, which are much better absorbed than salt forms of chromium, such as chromium chloride.⁹

R-Alpha-Lipoic Acid (R-ALA)

The R (+) isomer of alpha-lipoic acid (ALA) is the more bioactive form of this key thiol and antioxidant. Be aware that If an ALA supplement label does not specify R-ALA as the active ingredient, then it contains a racemic mixture of both R (+) and S (-) isomers of ALA, meaning the product will be less effective - per milligram - than a pure R-ALA supplement.
A large body of evidence suggests that R-ALA may:^10,11

1. Boost levels of glutathione - a crucial endogenous antioxidant in virtually all cells
2. Neutralize reactive oxygen species and mitigate oxidative stress
3. Enhance nutrient delivery to lean tissue (such as skeletal muscle)
4. Restore (and maintain) healthy insulin sensitivity
5. Support cardiovascular function by scavenging free radicals

Myo-Inositol & D-Chiro Inositol

Inositol is the collective term used in reference to a group of nine isomers that are cyclic polyols - a form of sugar alcohol.
Inositol was formerly known as vitamin B8 but is no longer considered a compound in the B vitamin family.
Inositol is a fairly ubiquitous molecule throughout the body, often bound to phosphate moieties that serve as a crucial component of the intracellular insulin-mediated activity.
We obtain insignificant amounts of inositol through diet; not nearly enough to have therapeutic effects.
In fact, most of the inositol found in the body is produced endogenously from glucose.
Thus, if you are on a low-carb/ketogenic diet, supplementing with inositol is a wise decision.
The most researched forms of inositol are called myo-inositol and D-chiro-inositol, which are typically sold either in capsules or as a sugar-like powder.
These particular forms of inositol hold significant promise as both insulin-sensitizing nutrients as well as a mood enhancers and stress fighters.^12,13

Berberine HCL

Berberine is a plant-derived compound with a variety of beneficial properties. Research suggests that berberine has intrinsic blood sugar-regulating properties, particularly by supporting healthy blood sugar and glucose transport protein (GLUT) function.¹⁴
As such, supplementing with berberine can support carbohydrate utilization and blood sugar balance.
Moreover, berberine appears to have selectivity towards muscle cells as opposed to fat cells when clearing nutrients from the blood.¹⁵
Muscle tissue serves as a favorable location for carbohydrate storage in the body since it is more likely to be used for energy rather than being converted to lipids and stored in adipose tissue (body fat).

Gymnema Sylvestre Extract

Gymnema sylvestre is a woody shrub natively found in tropical regions of India, Australia, and Africa.
This plant has been used in Ayurvedic/alternative medicine for thousands of years as a remedy for chronic inflammation and is now thought to be a potent herbal treatment for type-2 diabetes.
As research has grown, findings show that Gymnema sylvestre can not only inhibit the absorption of carbs and sugar but reduce cravings for sweets and enhance insulin sensitivity.¹⁶
Some clinicians have even gone to the length of calling Gymnema sylvestre “nature’s anti-diabetic drug”.
The major active constituent on Gymnema sylvestre responsible for these effects is gymnemic acid. It has been shown to block taste bud receptors that sense sweetness, reduce the intestinal absorption of glucose, and promote insulin sensitivity.¹⁷
This is the ideal supplement to take if you’re insulin resistant and plan on eating a carb-heavy meal.

Cinnamon Bark

Cinnamon, especially cinnamon bark, has been researched heavily in recent years due to its unique and beneficial profile of phytoconstituents.
Findings suggest that the antioxidants and compounds in cinnamon bark support healthy blood glucose levels after consuming a carbohydrate-rich meal by inhibiting the activity of the enzymes alpha-amylase and alpha-glucosidase.¹⁸
These enzymes are involved in carbohydrate digestion and glycolysis; thus when they are inhibited, carbohydrate digestion is delayed and/or blocked altogether, which supports healthy post-meal blood glucose values.
Theoretically, cinnamon bark supplements should pair well with Gymnema sylvestre extract supplements for helping block carb absorption and enhancing insulin sensitivity.

4-Hydroxyisoleucine (from Fenugreek Seed Extract)

4-hydroxyisoleucine is an atypical branched-chain amino acid (BCAA) found in fenugreek (Trigonella foenum-graecum) - a plant that has been used for medicinal purposes in civilizations dating as far back as 4000 BC.¹⁹
Recent research suggests that 4-hydroxyisoleucine is a natural remedy for metabolic syndrome as it helps stimulate secretion and ameliorate insulin resistance in both skeletal muscle tissue and the liver by promoting insulin receptor-associated phosphoinositide 3 (PI3) enzyme activity.²⁰
As such, stacking D-chiro-inositol and/or myo-inositol (which serve as precursors to PI3) with 4-hydroxyisoleucine would make for potent insulin-sensitizing supplement combination.

Key Takeaways about Insulin and Weight Loss

All in all, if your goal is to lose weight and keep it off, then you want your insulin sensitivity to be high. If you continually eat a sugar- and carb-rich diet while living a sedentary lifestyle, you put yourself at a higher risk of becoming insulin resistant and subsequently type-2 diabetic (making weight loss much more challenging than it should be).
However, losing weight with insulin resistance or type-2 diabetes is still very achievable with a sound diet (preferably one lower in carbs and higher in protein), diligent exercise several times per week, and the use of supplements that promote insulin sensitivity, as we discussed in this article.
Always be sure to consult with your primary care doctor if you’re diabetic and are planning on making drastic changes to your diet and/or dietary supplement regimen. It might help to purchase a blood glucose meter so you can assess how your blood sugar levels change quantitatively after you change your diet and start using supplements.

References

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2. Gholam, P. M., Flancbaum, L., Machan, J. T., Charney, D. A., & Kotler, D. P. (2007). Nonalcoholic fatty liver disease in severely obese subjects. The American journal of gastroenterology, 102(2), 399.
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8. Rabinovitz, Friedensohn, Leibovitz, Gabay, Rocas, & Habot. (2004). Effect of chromium supplementation on blood glucose and lipid levels in type 2 diabetes mellitus elderly patients. International journal for vitamin and nutrition research, 74(3), 178-182.
9. Chen, N. S., Tsai, A., & Dyer, I. A. (1973). Effect of chelating agents on chromium absorption in rats. The Journal of nutrition, 103(8), 1182-1186.
10. Saengsirisuwan, V., Perez, F. R., Kinnick, T. R., & Henriksen, E. J. (2002). Effects of exercise training and antioxidant R-ALA on glucose transport in insulin-sensitive rat skeletal muscle. Journal of Applied Physiology, 92(1), 50-58.
11. Ghibu, S., Richard, C., Vergely, C., Zeller, M., Cottin, Y., & Rochette, L. (2009). Antioxidant properties of an endogenous thiol: alpha-lipoic acid, useful in the prevention of cardiovascular diseases. Journal of cardiovascular pharmacology, 54(5), 391-398.
12. Mukai, T., Kishi, T., Matsuda, Y., & Iwata, N. (2014). A meta‐analysis of inositol for depression and anxiety disorders. Human Psychopharmacology: Clinical and Experimental, 29(1), 55-63.
13. Kennington, A. S., Hill, C. R., Craig, J., Bogardus, C., Raz, I., Ortmeyer, H. K., ... & Larner, J. (1990). Low urinary chiro-inositol excretion in non-insulin-dependent diabetes mellitus. New England Journal of Medicine, 323(6), 373-378.
14. Derosa, G., Maffioli, P., & Cicero, A. F. (2012). Berberine on metabolic and cardiovascular risk factors: an analysis from preclinical evidences to clinical trials. Expert opinion on biological therapy, 12(8), 1113-1124.
15. Cicero, A. F., & Ertek, S. (2009). Metabolic and cardiovascular effects of berberine: from preclinical evidences to clinical trial results. Clinical Lipidology, 4(5), 553-563.
16. Sugihara, Y., Nojima, H., Matsuda, H., Murakami, T., Yoshikawa, M., & Kimura, I. (2000). Antihyperglycemic effects of gymnemic acid IV, a compound derived from Gymnema sylvestre leaves in streptozotocin-diabetic mice. Journal of Asian natural products research, 2(4), 321-327.
17. Leach, M. J. (2007). Gymnema sylvestre for diabetes mellitus: a systematic review. The Journal of Alternative and Complementary Medicine, 13(9), 977-983.
18. Beejmohun, V., Peytavy-Izard, M., Mignon, C., Muscente-Paque, D., Deplanque, X., Ripoll, C., & Chapal, N. (2014). Acute effect of Ceylon cinnamon extract on postprandial glycemia: alpha-amylase inhibition, starch tolerance test in rats, and randomized crossover clinical trial in healthy volunteers. BMC complementary and alternative medicine, 14(1), 351.
19. Basch, E., Ulbricht, C., Kuo, G., Szapary, P., & Smith, M. (2003). Therapeutic applications of Fenugreek.(Fenugreek). Alternative Medicine Review, 8(1), 20-28.
20. Jette, L., Harvey, L., Eugeni, K., & Levens, N. (2009). 4-Hydroxyisoleucine: a plant-derived treatment for metabolic syndrome. Current opinion in investigational drugs (London, England: 2000), 10(4), 353-358.