Insulin Resistance, Parkinson's Disease, Consequences And What To Do About It

[chartist]

The topic of insulin resistance (IR) in PwP is not often discussed. Has your MDS or neurologist ever tested you for IR?

It is estimated that two thirds of people with PD who are not diabetic, have IR and very likely are not even aware they have IR as discussed here :

parkinson.org/blog/science-....

Here are some relevant quotes from the article :

' This study suggests that nearly two thirds of non-diabetic people with PD may be insulin resistant, despite having normal blood sugar, and in some cases, despite being lean. Thus, the big take-away from this study is that people with PD may want to have a more sensitive insulin test conducted, such as the HOMA-IR, to see if they have undiagnosed insulin resistance. There are several other IR tests as well. Which of these tests, or combinations thereof, might be best to evaluate a person’s IR is something to be discussed with one’s health care provider. '

' Another important take-away (although not specifically addressed in the Hogg et al. (2018) study), is that there are an increasing number of studies suggesting that IR negatively impacts dopamine functioning in the brain. Parkinson's symptoms, including tremors, stiffness, and slowness of movement, are caused by a lack of dopamine in the brain. This is particularly noteworthy for two reasons: One, the cornerstone of therapy for PD is the drug levodopa (also called L-dopa). Levodopa works by converting into dopamine and replenishing the brain's reduced supply; straight dopamine has difficulty crossing the blood/brain barrier. Two, IR is thought to precede the development of T2D by 10 to 15 years. Thus, having advanced notice of possible IR has great value, as IR is usually reversible. And while the jury is still out as to whether – and to what extent – having IR increases one’s risk for developing PD, taking proactive steps to mitigate one’s risk for developing T2D has profound long and short-term health benefits. '

ncbi.nlm.nih.gov/books/NBK5...

The list below is from the above article link.

So even if you don't have diabetes and you have a lean body, you can still be insulin resistant and this can affect PwP and people in general, negatively. IR can cause any of the following :

1. Hyperglycemia

2. Hypertension

3. Dyslipidemia (Elevated cholesterol and triglycerides)

4. Visceral Adiposity

5. Hyperuricemia (Elevated uric acid levels in the blood)

6. Elevated Inflammatory Markers

7. Endothelial Dysfunction

8. Prothrombotic State (Blood clotting)

9. Arterial Damage

10. Diabetes

iherb.com/blog/insulin-resi...

Many people who are insulin resistant are not even aware that they are and if your doctor doesn't test you and tell you that you are insulin resistant, how will you even have a clue? There are signs that can help you determine if you should ask your doctor to test you for IR. Here is a list of common ones :

High blood pressure (hypertension)

Overweight

Obesity

Skin tags (especially the neck or groin)

High cholesterol

High triglycerides

Fatty liver

Prediabetes

Diabetes

Enlarged prostate

Heart disease

Polycystic ovarian syndrome (abnormal periods)

I would look at IR as one step, higher up in a cascade of negative health steps where almost all roads lead to a worsening of health such as diabetes, CVD or organ damage! This cascade also involves ever increasing oxidative stress levels and elevated inflammatory markers in the body. This is a path that none of us want to go down or stay on and PwP certainly don't need IR.

So, what can we do to reduce insulin resistance and improve insulin sensitivity? A healthful diet is a very good starting point if you are able to stick to it, but for various reasons, people are often not able to maintain such a diet.

Regular exercise is another effective means to reduce insulin resistance while increasing insulin sensitivity. For some PwP, exercise is a difficult proposition if not almost impossible.

BERBERINE

There are also supplements that can help to reduce IR. One that I have written about before is Berberine which can reduce insulin resistance while increasing insulin sensitivity as discussed here:

ncbi.nlm.nih.gov/pmc/articl....

Here is a relevant quote :

' Berberine improves physiological stimulation of glucose via cascade reaction of insulin-like growth factor-1 (IGF-1), thus inducing secretion of insulin in the body, reducing insulin resistance, and improving sensitivity of liver, muscle tissues and fat to insulin (16). '

Berberine has also been discussed at length on this forum as being beneficial for PD via multiple pathways and mechanisms. Similarly, berberine is also useful for AD.

GRAPE SEED PROANTHOCYANIDIN EXTRACT

Another supplement that has shown the ability to reduce insulin resistance in people is Grape Seed Proanthocyanidin Extract (GSPE) as discussed in the following human study :

pubmed.ncbi.nlm.nih.gov/333...

Here is a relevant quote from the randomized controlled trial (RCT) :

' Forty-two participants completed the trial. After the intervention, the age, sex, baseline values, energy intake and physical activity as a covariate adjusted using ANCOVA for determine differences between groups. The MD (mean difference ±SEM) of HOMA-IR between the GSE group (-1.46 ± 0.45) and the placebo group (-0.48 ± 0.47), (p = 0.020), and the MD of insulin between the GSE group (-7.05 ± 2.11) and the placebo group (-1.71 ± 2.12), (p = 0.024), were significant. Although changes were observed in other variables, they were not statistically significant. '

Interesting about this GSPE study above, is the dose they used. Just 100mg per day to reduce IR. I take a minimum of 1200 mg/day.

MAGNESIUM

Another supplement that has shown the ability to reduce insulin resistance is Magnesium. Magnesium is significantly negatively correlated with IR. Magnesium is highly underrated for diabetes. The following study (2021) is interesting :

pubmed.ncbi.nlm.nih.gov/345...

Here is an interesting quote from the study :

' HOMA-IR increases as the Mg level decreases in advanced ages without obesity, especially in men with low eGFR.'

eGFR is a marker for how well the kidneys are filtering.

In this next study magnesium is shown to significantly lower insulin resistance in rheumatoid arthritis(RA) patients thus potentially reducing their chances of getting diabetes. RA patients are at increased risk of getting diabetes.

ncbi.nlm.nih.gov/pmc/articl...

Here is a relevant quote from the study :

' Statistically significant differences were found between FBS, insulin and HOMA-IR before and after consumption of oral magnesium (p<0.05). Our data suggested that magnesium supplementation reduces FBS, insulin and HOMA-IR in patients with rheumatoid arthritis. Thus, magnesium supplements may be an alternative method for prevention of type 2 diabetes in RA patients. '

CEYLON CINNAMON

The next supplement I want to mention for IR is Cinnamon, and of course the preferred form is Ceylon Cinnamon. Cinnamon also significantly lowers IR as discussed in the following study :

ncbi.nlm.nih.gov/pmc/articl...

Here is a relevant study quote :

' Weight and BMI decreased significantly in all intervention groups. The consumption of metformin and cinnamon significantly decreased insulin resistance (HOMA-IR) in comparison to the placebo and ginger groups (P < 0.05). '

VITAMIN D

The last supplement I would like to discuss and possibly the most important based on its multitude of positive health effects is vitamin D.

The following study discusses how in recent years it is becoming clearer through studies and research that vitamin D is a very significant factor when it comes to IR and vitamin D was shown to improve insulin sensitivity in this study at 5000 iu/day:

eje.bioscientifica.com/view...

Here is an important quote from the 6 month study in humans :

' At 6 months, mean 25(OH)D reached 127.6 ± 26.3 nmol/L and 51.8 ± 16.5 nmol/L in the treatment and placebo groups, respectively (P < 0.001). A beneficial effect of vitamin D3 compared with placebo was observed on M-value (mean change (95% CI): 0.92 (0.24–1.59) vs −0.03 (−0.73 to 0.67); P = 0.009) and disposition index (mean change (95% CI): 267.0 (−343.4 to 877.4) vs −55.5 (−696.3 to 585.3); P = 0.039) after 6 months. '

The M-value mentioned above is the value used for insulin sensitivity and the study shows a statistically significant positive change.

Here is another relevant quote from the study :

' In conclusion, this study showed that high-dose vitamin D supplementation for 6 months significantly improved peripheral insulin sensitivity, as assessed by the hyperinsulinemic-euglycemic clamp, and β-cell function in individuals at high risk of diabetes or with newly diagnosed type 2 diabetes.

So these five supplements have all shown the ability in people to decrease insulin resistance and or increase insulin sensitivity which is a healthful venture for people in general, whether you have diabetes or not and especially if you have PD or other disease.

There are many supplements that can reduce insulin resistance, but these five have very good safety profiles, studies to support their use for this purpose, are relatively inexpensive and have the ability to offer other health benefits with less chance for negative side effects.

Art

[park_bear]

Ceylon cinnamon beneficial in Parkinson's also:

healthunlocked.com/cure-par...

[MarionP in reply to park_bear]

7Indeed, I ran across that somewhere and I forgotten it, excellent idea. I would have been using it long before now except I just don't like cinnamon, have never been able to get round it. It's okay on cinnamon rolls with some sugar frosting, once in awhile and that's about it as far as cinnamon goes for me. Too bad. In fact, the aversion goes this far: I very much loved the whole Dune original book series greatly, except for that he chose cinnamon as the centerpiece, kept thinking why couldn't he have chosen hashish.

[MBAnderson]

Art, will you be my doctor?

[chartist in reply to MBAnderson]

Dear Marc,

Regarding if I can be your doctor :

Possibly, but I have to make sure we accept your insurance first. You'll have to contact my office manager during regular business hours. We're open from 11:00 am ~ 2:00pm and of course we are closed from 12:00 pm to 1:00 pm for lunch, but if your insurance is acceptable, we can probably squeeze you in by early 2025 and as always, if this is a medical emergency, dial 911 immediately. 😂😂😂😂😂

Art

[MBAnderson in reply to chartist]

ha

[MarionP]

Hey Art Very interesting, important, timely post, really important and I'm not just making that up. Excellent thinking excellent association, we should all be thanking you.

[chartist in reply to MarionP]

Thank you, for saying so!

If you delve just a little deeper, it will be a bit surprising to see how many diseases have IR as an often seen component.

Art

[MarionP in reply to MarionP]

Yes, that's part of why I realized we should be thanking you, I'm aware of quite a bit of that and we don't do enough to realize that insulin resistance is kind of one of those keystone linchpin type situations like vitamin D and zinc and B12 and magnesium and such like.

[chartist]

I'm not positive, but I believe the FDA does not actually have a drug that is specific for IR, but several diabetes drugs like metformin do reduce IR, however that would be considered off label usage and I think some doctors are going to be reluctant to prescribe a diabetic drug for off label use possibly due to liability issues, so this may partially explain why doctors don't test for IR on a regular basis? None of my doctors have ever tested me for IR.

Yes, I just looked and this link says that there is no drug specifically approved for IR :

diabetes.org/healthy-living....

I wonder if that means that the FDA does not consider IR important enough or enough of a problem to deal with?

Art

[JustJeff]

As a type 2 diabetic with PD this is very interesting " increasing number of studies suggesting that IR negatively impacts dopamine functioning in the brain"

[chartist in reply to JustJeff]

JJ,

Yes, that is sometimes mentioned, but testing for it seems to be not very common and that is too bad because insulin resistance seems to be treatable without too much trouble and that simple treatment seems like it should help protect dopamine and lower the excess oxidative stress as well as inflammation seen in PwP and that seems like it would slow progression.

Art

[chartist in reply to JustJeff]

JJ,

Several very good supplements for diabetes are berberine at 1500 mg/day in three divided doses of 500 mg each at breakfast lunch and dinner.

Magnesium glycinate at the daily RDA of elemental magnesium which requires 3 to 4 capsules per day to get into that range with most magnesium glycinate supplements.

Vitamin K2M7 at 200 mcg/day minimum.

Vitamin D at 5000 iu /day minimum.

Synbiotics at high dose. Fermented foods.

These can all improve the diabetic state and improve IR.

Art

[Nikosmom]

thanks for your posting. Very thought provoking.

[chartist in reply to Nikosmom]

I'm glad you found it thought provoking!

Art

[Pegcity]

Fenugreek can also help with IR. Indian studies under "methi," often consumed by soaking in water and drinking the liquid, recommend it to reduce blood glucose and IR.

[chartist in reply to Pegcity]

Thank you for another insulin resistance lowering method using fenugreek!

Art

[Stillstandingstill]

Mirabegron/Betmiga, which I am on for my pesky bladder, seems to have some potential side benefits with regards to IR.

mdpi.com/2673-4168/2/4/32#:....

[chartist in reply to Stillstandingstill]

Does it also help for the purpose you are using it for?

Art

[Stillstandingstill in reply to chartist]

It has helped. Better and safer for cognition than tolterodine too. I am keeping an eye on my BP though as it can increase that.

[chartist in reply to Stillstandingstill]

Glad it is working for that purpose because it seems like it can be a nuisance to deal with.

Art

[rebtar]

Art, is the triglyceride/HDL ratio a good indicator? My A1C and triglyceride/HDL are nice and low.

[chartist in reply to rebtar]

Yes, the tg/hdl ratio is considered a good indicator for IR, but the list in the original post are also considered potential indicators for IR.

Art

[slimweiss]

is there a recommended dosage for each of these? Also what form of magnesium?

[chartist in reply to slimweiss]

The dosage for berberine is generally 1500 mg/day in three divided doses of 500 mg at breakfast, lunch and dinner.

GSPE, most bottles are 400 mg capsules and that is generally the recommended dose, but the bottle I take has 400 mg capsules also, but they recommend taking 3 a day or 1200 mg/day and that is what I take.

The RDA for magnesium is 400~420 mg for men and 310~320 mg for women. This is for elemental magnesium, but many manufacturers add other components which can seem like a lot of magnesium, but it isn't. As an example, I take magnesium glycinate which is considered a very bioavailable form of magnesium. You have to pay attention to what the bottle label shows though with each manufacturer. My bottle say 400 mg on the label, but in order to get that 400 mg, you have to take 4 capsules and each capsule is about 500 mg because of the added glycinate.

Same with another popular form of magnesium called magnesium l threonate. You have to take roughly 2000 mg worth of capsules in order to get around 400 mg of actual magnesium. Most products suggest 3 to 4 capsules a day in order to get roughly 400 mg of magnesium.

Cinnamon at the label suggested dose.

Vitamin D, you can get tested for by your doctor to get into the upper half of the reference range which is 30 to 100 ng/ml . I take 5000 iu to 10,000 iu per day, but this can vary from person to person and that is why it is better to test.

Art

[slimweiss in reply to chartist]

thank you so much. I will be ordering all of these today! I would have you as my doctor too! 👍🙏🤣

[chartist in reply to slimweiss]

With the berberine, I would start with one cap per day with your main meal to make sure you tolerate it and then if no problem work up to two and then possibly three. The 1500 mg/day amount is what is suggested for diabetics.

The same with GSPE start with 400 mg/day and add only if you think you are tolerating it well and need more. Keep in mind that the GSPE study that I linked to in the original post only used 100 mg per day to good effect, so 400 mg/day may be sufficient.

Art

[slimweiss in reply to chartist]

I think I could bump up the berberine as I have already been taking it. Same for my hwp. We also do Liposomal Vit. D already at 5000ui. We take magnesium L-threonate so I'll add the one you suggest along with the others. thank you!!!

[chartist in reply to slimweiss]

Good luck !

Art

[Sydney75 in reply to chartist]

Berberine did work for my HWP lowering A1C too. (He's not diabetic). However, I after about 3 months he did develop some stomach upset which is a side effect. Interestingly, the following comments on the Natural Database (Natural Medicines subscriber site) has listed the following interaction with probiotics and as he takes the PS128, I don't want to reduce any benefit bc its $$.

PROBIOTICS: The growth of some probiotic species is inhibited by berberine, which might reduce probiotic effectiveness.

- Details

In vitro research shows that berberine can inhibit the growth of certain probiotic species, including Bifidobacterium longum and B. bifidum, but not Lactobacillus acidophilus or L. casei (34200). Theoretically, berberine may inhibit the beneficial effects of probiotics containing Bifidobacterium species. See other products with probiotic activity here.

Also it interacts with CBD

Theoretically, berberine might cause QTc prolongation when used with CBD.

- Details

Laboratory research suggests that berberine and CBD inhibit cardiac human hERG channels, potentially leading to QTc prolongation. Also, CBD has been shown to inhibit cytochrome P450 3A4 (CYP3A4), of which berberine is a substrate. In one case report, a 56-year-old patient presenting with syncope and a 1-month history of dizziness was found to have a QTc interval of 667 msec. The patient reported taking berberine 250 mg daily for around 6 weeks and hemp oil products containing CBD (24-61 mg/mL) and cannabigerol (CBG) (1 mg/mL) at doses up to 6 times greater than recommended for up 4 months.

I realize both of these "reactions" are theoretical, drug interaction warnings listed are to be cautious with use of diabetic, blood pressure and CNS depressant meds as berberine can potentate medications.

Fenugreek will make urine smell funny (maple syrup), does not seem to have as many reactions to meds and other supplements. Might be a good choice for Hwp.

Thanks for research!

[chartist in reply to Sydney75]

Regarding these anti IR supplements, it doesn't seem likely that it would take all five to effectively lower IR. Vitamin D, magnesium and GSPE seem like they should be a very effective combo and then there is still cinnamon and as I mentioned a little earlier today, astaxanthin if needed, so berberine may not be needed by your husband. However, berberine has shown some benefit for PD. Problem solved!

Of course PS128 is plantarum and there was no mention of that in the article that I noticed.

Art

[Zardoz]

Maitake mushroom is another good supplement for sugar control.

[chartist in reply to Zardoz]

Yes, and maitake improves insulin sensitivity. I was not aware of that, thank you for posting it.

Art

[Sydney75 in reply to Zardoz]

Having never ventured into mushrooms I looked it up on the same site as I did berberine and this is the information listed under Mechanism of Action:

Hypoglycemic effects: There is interest in using maitake mushroom for its hypoglycemic effects. Enhanced insulin-hypoglycemic activity has been observed in rats consuming a specific glycoprotein extracted from maitake mushroom (61238). An alpha-glucan from the fruit body of maitake mushroom has also exhibited an antidiabetic effect in mice (61236). Antidiabetic effects of maitake mushroom extracts have been shown in other animal studies, resulting in reduced levels of blood glucose in diabetic models (1212,61217,61222,61226). In these studies, depending on the model, insulin levels were increased or decreased, and fructosamine was decreased. Decreased glycated hemoglobin has also been observed in an animal model after treatment with maitake mushroom powder (61226). In human research, maitake mushroom reduced blood glucose in patients with type 2 diabetes (8188). The extract responsible for improving insulin resistance is believed to be the water-soluble glycoprotein called "SX-fraction" or MSX (17131). Polysaccharides also appear to have a hypoglycemic effect, possibly by activating insulin receptors (1212,8188). Another theory is that maitake mushroom can improve glucose tolerance by activating peroxisome proliferator-activated receptor delta (PPARd), which seems to increase insulin sensitivity. Research in obese mice models fed a high-fat diet shows that consuming a lipid soluble maitake mushroom extract activates PPARd-target genes and improves glucose tolerance (99569).

I try to check new supplements for my HWP as I don't want to give him anything that interacts with any meds he takes.

An earlier post I read today had a video addressing negative of resveratrol, I checked the site today and did not see the negative impacts the speaker in the video spoke about but may take it out of our stack.

Reishi mushroom is considered "possibly effective" in lowering lipid panel and BPH (Prostate).

Several of these supplements must be stopped before any surgery.

[chartist]

This December 2021 study in people suggests that just 12 mg of Astaxanthin per day lowers insulin resistance also :

ncbi.nlm.nih.gov/pmc/articl...

Here is a relevant quote :

' The Matuda index, which is one of the parameters of insulin resistance, was improved in the ASTX group compared to that before supplementation. '

Art

[Sydney75 in reply to chartist]

Very good report on Astaxanthin mechanism of action:

Antioxidant effects: Astaxanthin is a powerful antioxidant that is structurally similar to beta-carotene (8467). It contains the highest relative antioxidant activity when compared with alpha-tocopherol, alpha-carotene, beta-carotene, lutein, and lycopene (10634). Cell culture research shows that astaxanthin inhibits glycated protein/iron chelate-induced cytotoxicity by reducing the generation of reactive oxygen species (ROS) in human umbilical-vein endothelial cells (32680). Clinical research shows that taking astaxanthin 4-20 mg daily for 1 to 12 months reduces blood levels of malondialdehyde (MDA), a marker of oxidative stress (98768,107960). Interestingly, greater reductions in MDA are observed in patients with type 2 diabetes, and with doses of 11-13 mg daily. Additionally, astaxanthin may reduce levels of superoxide dismutase in overweight patients, but not in healthy individuals, when compared with placebo (107960). In patients with polycystic ovary syndrome (PCOS), astaxanthin improved the total antioxidant status but did not affect MDA, catalase, or superoxide dismutase (109775).

Some preliminary research suggests that the antioxidant effects of astaxanthin can protect against neurodegenerative diseases. Cell culture and animal research shows that astaxanthin prevents beta-amyloid-induced oxidative damage to red blood cells and dopaminergic cells. Theoretically this may help prevent the progression of Alzheimer disease and other dementias (32695,32702). Also, preliminary research in humans shows that astaxanthin can help reduce the accumulation of phospholipid hydroperoxides in erythrocytes. Abnormal accumulation of phospholipid hydroperoxides is associated with dementia (32700). Also, oxidative stress is thought to contribute to the pathogenesis of Parkinson disease. Cell culture and animal research shows that astaxanthin reduces oxidative stress-induced cytotoxicity of dopaminergic neurons, suggesting that it may protect against oxidative stress-induced neurodegeneration associated with Parkinson disease (32669,32673,32676,32697). Animal research also shows that the antioxidant effects of astaxanthin helps protect against ischemia-induced injury to brain tissue (32674).

Not as much is known about this supplement, site did not list too many contraindications. Take with a meal ... low bioavailability.

Pharmacokinetics

Absorption: Orally, astaxanthin is absorbed in the intestines (32658). However, because astaxanthin is a highly lipophilic compound, it has low bioavailability (32644). Human absorption of astaxanthin ranges from 6% to 34% after 4 hours (107961). The bioavailability may be increased when astaxanthin is encapsulated in a lipid-based formation (32622,32688). Also, the absorption of astaxanthin may be increased when taken after a meal (32682,107961).

Distribution: Animal research shows that, when taken orally, astaxanthin is largely distributed to muscle and heart tissue (32722). Astaxanthin can also cross the blood-brain barrier, as well as accumulate in the dermis and epidermis (96884).

Excretion: Preliminary clinical research shows that the elimination half-life of astaxanthin, taken orally at a dose of 40 mg, is about 16 hours, with a monophasic curve (32622). Other preliminary clinical research suggests that the elimination half-life of astaxanthin, taken orally at a dose of 100 mg, is about 52 hours (

[chartist in reply to Sydney75]

Those are some of the reasons that I take astaxanthin, but not all.

Art

[Sydney75 in reply to chartist]

Yes the site listed several other good "actions" I think this is a good choice to add to stack. Now to find a high quality bio-available brand that is not to pricey.

[chartist in reply to Sydney75]

I use this one :

amazon.com/Astaxanthin-Supp...

As I wrote about previously on the forum here :

healthunlocked.com/cure-par...

Art

[Sydney75 in reply to chartist]

Thank you!

[chartist]

This new study abstract (March 15, 2023) is just an animal study, but it illustrates many of the ways that Berberine reduces insulin resistance caused by high fructose :

pubmed.ncbi.nlm.nih.gov/369...

Here is a relevant quote from the study :

' Notably, berberine could increase the level of AMP and the ratio of AMP/ATP, then further activate AMPK. Mechanistic experiments revealed that berberine suppressed the expression of adenosine monophosphate deaminase 1 (AMPD1) and promoted the expression of adenylosuccinate synthetase (ADSL). Taken together, berberine exerted excellent therapeutic effect on insulin resistance. And its mode of action may be related to the AMP-AMPK pathway by regulating AMPD1 and ADSL. '

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Art