Diabetes Type 2, PD and Berberine

[chartist]

Diabetes is a common disease that affects many Americans and 90 to 95% of diabetics have Type 2 Diabetes Mellitus (T2DM). I will be discussing T2DM and one option to help deal with it effectively based on multiple studies. Type 1 Diabetes (T1D) is significantly less common so I will focus this discussion on T2DM. T2DM occurs in 1 out of 10 in the US while prediabetes occurs in 1 in 3 illustrating what a huge health concern T2DM really is.

cdc.gov/diabetes/library/fe....

T2DM leaves patients at increased risk for PD according to the following article. Here is a quote from the article :

>>> ' During a mean follow-up period of 18.0 years, 324 men and 309 women developed incident Parkinson's disease. Age- and study year–adjusted hazard ratios of incident Parkinson's disease among subjects with type 2 diabetes, compared with those without it, were 1.80 (95% CI 1.03–3.15) in men, 1.93 (1.05–3.53) in women, and 1.85 (1.23–2.80) in men and women combined (adjusted also for sex). Further adjustment for BMI, systolic blood pressure, total cholesterol, education, leisure-time physical activity, smoking, alcohol drinking, and coffee and tea consumption affected the results only slightly. The multivariate adjusted association between type 2 diabetes and the risk of Parkinson's disease was also confirmed in stratified subgroup analysis. '<<<

care.diabetesjournals.org/c...

Treating T2DM effectively, early in the disease process can go a long way in preventing many of the health complications seen in advanced stage T2DM which can be very disabling .

What Are The Symptoms Of T2DM

mayoclinic.org/diseases-con...

Increased thirst

Frequent urination

Increased hunger

Unintended weight loss

Fatigue

Blurred vision

Slow-healing sores

Frequent infections

Numbness or tingling in the hands or feet

Areas of darkened skin, usually in the armpits and neck

What Are The Causes Of T2DM

webmd.com/diabetes/type-2-d...

Your pancreas makes a hormone called insulin. It helps your cells turn glucose, a type of sugar, from the food you eat into energy. People with type 2 diabetes make insulin, but their cells don't use it as well as they should.

At first, your pancreas makes more insulin to try to get glucose into your cells. But eventually, it can't keep up, and the glucose builds up in your blood instead.

Usually, a combination of things causes type 2 diabetes. They might include:

Genes. Scientists have found different bits of DNA that affect how your body makes insulin.

Extra weight. Being overweight or obese can cause insulin resistance, especially if you carry your extra pounds around your middle.

Metabolic syndrome. People with insulin resistance often have a group of conditions including high blood sugar, extra fat around the waist, high blood pressure, and high cholesterol and triglycerides.

Too much glucose from your liver. When your blood sugar is low, your liver makes and sends out glucose. After you eat, your blood sugar goes up, and your liver will usually slow down and store its glucose for later. But some people's livers don't. They keep cranking out sugar.

Bad communication between cells. Sometimes, cells send the wrong signals or don't pick up messages correctly. When these problems affect how your cells make and use insulin or glucose, a chain reaction can lead to diabetes.

Broken beta cells. If the cells that make insulin send out the wrong amount of insulin at the wrong time, your blood sugar gets thrown off. High blood sugar can damage these cells, too.

What Are The Risk Factors For T2DM

mayoclinic.org/diseases-con...

Factors That May Increase Your Chances For T2DM :

Weight. Being overweight or obese is a main risk.

Fat distribution. Storing fat mainly in your abdomen — rather than your hips and thighs — indicates a greater risk. Your risk of type 2 diabetes rises if you're a man with a waist circumference above 40 inches (101.6 centimeters) or a woman with a measurement above 35 inches (88.9 centimeters).

Inactivity. The less active you are, the greater your risk. Physical activity helps control your weight, uses up glucose as energy and makes your cells more sensitive to insulin.

Family history. The risk of type 2 diabetes increases if your parent or sibling has type 2 diabetes.

Race and ethnicity. Although it's unclear why, people of certain races and ethnicities — including Black, Hispanic, Native American and Asian people, and Pacific Islanders — are more likely to develop type 2 diabetes than white people are.

Blood lipid levels. An increased risk is associated with low levels of high-density lipoprotein (HDL) cholesterol — the "good" cholesterol — and high levels of triglycerides.

Age. The risk of type 2 diabetes increases as you get older, especially after age 45.

Prediabetes. Prediabetes is a condition in which your blood sugar level is higher than normal, but not high enough to be classified as diabetes. Left untreated, prediabetes often progresses to type 2 diabetes.

Pregnancy-related risks. Your risk of developing type 2 diabetes increases if you developed gestational diabetes when you were pregnant or if you gave birth to a baby weighing more than 9 pounds (4 kilograms).

Polycystic ovary syndrome. Having polycystic ovary syndrome — a common condition characterized by irregular menstrual periods, excess hair growth and obesity — increases the risk of diabetes

Areas of darkened skin, usually in the armpits and neck. This condition often indicates insulin resistance.

What Are The Complications That Can Occur From T2DM

mayoclinic.org/diseases-con...

Type 2 diabetes affects many major organs, including your heart, blood vessels, nerves, eyes and kidneys. Also, factors that increase the risk of diabetes are risk factors for other serious chronic diseases. Managing diabetes and controlling your blood sugar can lower your risk for these complications or coexisting conditions (comorbidities).

Potential complications of diabetes and frequent comorbidities include:

Heart and blood vessel disease. Diabetes is associated with an increased risk of heart disease, stroke, high blood pressure and narrowing of blood vessels (atherosclerosis).

Nerve damage (neuropathy) in limbs. High blood sugar over time can damage or destroy nerves, resulting in tingling, numbness, burning, pain or eventual loss of feeling that usually begins at the tips of the toes or fingers and gradually spreads upward.

Other nerve damage. Damage to nerves of the heart can contribute to irregular heart rhythms. Nerve damage in the digestive system can cause problems with nausea, vomiting, diarrhea or constipation. For men, nerve damage may cause erectile dysfunction.

Kidney disease. Diabetes may lead to chronic kidney disease or irreversible end-stage kidney disease, which may require dialysis or a kidney transplant.

Eye damage. Diabetes increases the risk of serious eye diseases, such as cataracts and glaucoma, and may damage the blood vessels of the retina, potentially leading to blindness.

Skin conditions. Diabetes may leave you more susceptible to skin problems, including bacterial and fungal infections.

Slow healing. Left untreated, cuts and blisters can become serious infections, which may heal poorly. Severe damage might require toe, foot or leg amputation.

Hearing impairment. Hearing problems are more common in people with diabetes.

Sleep apnea. Obstructive sleep apnea is common in people living with type 2 diabetes. Obesity may be the main contributing factor to both conditions. It's not clear whether treating sleep apnea improves blood sugar control.

Dementia. Type 2 diabetes seems to increase the risk of Alzheimer's disease and other disorders that cause dementia. Poor control of blood sugar levels is linked to more-rapid decline in memory and other thinking skills.

As you can see from the above, T2DM can very easily become a menace to your overall health so taking steps early on to try and control T2DM makes plenty of sense.

What Steps Can We Take To Try and Prevent T2DM

healthline.com/nutrition/pr...

1. Cut sugar and refined carbs from your diet.

2. Exercise Regularly.

3. Drink Water as your primary beverage.

4. Lose weight if you are overweight or obese.

5. Quit Smoking.

6. Follow a very low carb diet.

7. Watch meal portion sizes.

8. Avoid sedentary behaviors

9. Eat a high fiber diet.

10. Optimize vitamin D levels.

11. Minimize your intake of processed foods.

12. Include coffee or tea as part of your diet.

13. Consider taking natural herbs.

In conjunction with the above improvements, dietary changes and lifestyle changes, I would like to discuss the herb Berberine and the studies which show it to be useful in the fight against T2DM through multiple methods of action.

Berberine To Help Multiple Symptoms Of T2DM And Increase Dopamine

In this first and important recent study (2/2021), it is shown that Berberine regulates the gut microbiota to produce bacteria that increases L-dopa in the gut and also increases dopamine in the brain and can potentially ameliorate Parkinson's Disease in mice and humans.

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

The following study suggests that Berberine protects against the inflammatory NLRP3 inflammasome via ameliorating autophagic impairment in the MPTP induced mouse model of PD. At a minimum, a read of the brief abstract of this full study is worthwhile.

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

This next study discusses the potential of Berberine in neurodegenerative diseases such as AD, PD and trauma induced neurodegeneration.

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

In this study, Berberine shows that it is has somewhat similar effects as the common T2DM drug, Metformin.

pubmed.ncbi.nlm.nih.gov/295...

This next study is interesting in that it shows that Berberine can also protect against Metformin associated lactic acidosis (MALA).

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

The following study abstract shows that Berberine lowers blood glucose in T2DM patients by increasing insulin receptor expression.

pubmed.ncbi.nlm.nih.gov/198...

In this next study, Berberine is shown to be synergistic with Metformin where both together are better than either one alone at lowering high glucose induced lipogenesis. For those who are not familiar with Metformin, it is considered a first line pharmaceutical for treating T2DM. Here is a quote from the study :

>>> ' The combination of Metformin and Berberine exerted synergistic lipid-lowering effects on HepG2 cells by reducing total lipid content, triglyceride level, and the expression of the genes involved in lipogenesis. '<<<

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

This next abstract adds more data to the idea that Berberine and Metformin may work well together.

pubmed.ncbi.nlm.nih.gov/304...

This is an older study (2008), but it goes into significant detail of many of the ways in which Berberine may be beneficial for patients in the fight against T2DM. It also discusses the lipid and triglyceride lowering effects of Berberine and discusses the dosing used in the study as 1,500 mg total Berberine per day in 3 divided doses of 500 mg each dose spread throughout the day. Here is a quote from the study :

>>> ' In conclusion, this pilot study indicates that berberine is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism. '<<<

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

Dosing of Berberine Based On The Information Contained In This Article Below

In the following article, dosing of berberine at 1,500 mg per day divided into 3 equal doses of 500 mg each during the day is mentioned as a possible dosing schedule, along with an explanation of why.

healthline.com/nutrition/be...

There are many more studies discussing the use of Berberine as adjunctive treatment for T2DM and the above should give a good idea of how useful Berberine can be.

Conclusion

The above studies and information illustrate that Berberine has hypoglycemic effects, lipid lowering effects and has synergy with the front line T2DM pharmacological treatment, Metformin, in T2DM patients and is worth discussing with your doctor for pre-diabetes and T2DM. If you search the internet, you will also find plenty of anecdotal evidence suggesting that Berberine is useful in T2DM.

As always, I am not a doctor and as such can not recommend Berberine as a treatment for T2DM nor can I offer dosing advice, but fortunately, dosing advice is given in one study and one article above! In any case, given the serious nature of T2DM, consulting your doctor or healthcare professional before starting Berberine is needed.

Where To Get Berberine

Berberine is readily available from most on line supplement suppliers.

Art

[rescuema]

As I've mentioned before, Berberine is one of the most powerful OTC supplements available. If anyone is interested, I suggest starting slow because the initial effects can be disorienting - diarrhea (antibacterial effect), weakness, headache, nausea, etc., even at 500mg/day so ramp up very slowly. Its effect is pretty immediate on the glucose level, and the remnant effect lasts even through periodic cycling. The only thing I don't like about it is that it seems to cause my eyelashes to fall out - not good, but this is n=1 and I've not heard of anyone else reporting the issue although I've repeatedly noticed the effect on myself. I believe similar concerns are reported on Metformin related to hair loss in some people.

[chartist in reply to rescuema]

I hadn't heard about the eyelashes before, but that seems odd. Gastro disruption is a known effect as it modulates the gut microbiome in a positive way. The gastro issues are very individual as some people can go to 1,500 mg straightaway with no issues while others may need to work their way up as the gut biome adjusts. The synergy with metformin is a definite plus for those already taking metformin. The positive effects toward PwP are definitely a plus!

It does have many positive effects in humans and animals, but definitely a plus in the fight against T2DM!

Art

[rescuema in reply to chartist]

I agree - most would agree that hair loss is better than limb/vision/nerve loss that could happen in uncontrolled diabetes. However, because I'm able to control my glucose level through diet/exercise, I choose to use the alternative such as Benfotiamine +ALA that also has effective glucose modulating effect rather than more powerful berberine most of the time. I do get help through Berberine on Thanksgiving or other times I indulge. If not for the eyelash loss, I'd be taking it more often. I believe this issue is more rare than usual, so don't let this personal report stop you from trying. I have more faith in it than Exenatide.

[chartist in reply to rescuema]

It's just your eyelashes and not other hair? That's really unusual. I know chemo drugs can cause hair loss, but that's usually due to the high oxidative stress levels that they generate to kill cancer cells.

Art

[rescuema in reply to chartist]

Well, clumps of eyelash loss are definitely more noticeable, but I'd say it also affects other hair if I continued the supplement. The good news is that they grow back. Since berberine has an anti-cancer effect, it may have something to do with interrupting the cell growth cycle - at least that's how I see it.

[rescuema in reply to chartist]

On a related note, here's a report on Metformin on hair loss, so I'd say it might be ok for most people even for berberine.

ehealthme.com/ds/metformin/...

[chartist in reply to rescuema]

The 1.25% seems reasonable in terms of risk to reward for this health issue.

Art

[rescuema in reply to chartist]

If it is indeed that low, yes. Often people fail to notice the correlation after months/years - about 92% of the report is from women and others may assume it's age-related.

[Hidden in reply to rescuema]

Wow, more faith in Berberine than Exenatide, that says a lot about both. To clarify, faith in its use for PD or diabetes?

[Hidden in reply to rescuema]

Side note: I believe TUDCA is causing hair loss for me. I have therefore reduced my intake

[laglag]

Thanks for the info. I read everything you wrote but I haven't had a chance to open the attachments yet. My A1C has been going up the last couple of years and it's concerning my doctor. I'm trying to lower my carbs, but it's sooo tough.

Keep fighting!🥊

[chartist in reply to laglag]

The Berberine is noted for lowering A1C among other benefits. It is considered a fairly potent antioxidant so that should also be helpful. Some people also report weight loss, but this is not consistent for everyone.

Art

[chartist]

A new abstract of an RCT study came out today that used 250 mg/melatonin/day on T2DM patients and this is very important for 2 reasons. One the use of high dose melatonin (HDM) was helpful for the patients and the dose of 250 mg/day is fairly high, however, I notice a trend toward HDM in studies these days compared to the relatively low dose studies that were previously the norm. Here is a link to that abstract :

pubmed.ncbi.nlm.nih.gov/337...

What is important to see aside from the high dose of melatonin used in this study is the fact that this study was only 8 weeks long and the improvement in multiple parameters of disease markers were notably improved so quickly, illustrating the effectiveness of HDM and the broad spectrum of effects it has while also having a very good safety profile.

This could mean that Berberine and Melatonin may be quite useful for people with T2DM and other diseases.

Now if only they would do a similar study at this dose of melatonin (250 mg/day) in PwP!

Art

[LAJ12345]

My husband has used it with Allimed (garlic) regularly for a couple of years for rosacea and acne which has completely gone. And his fungal toenail he has had forever is gradually looking better. He used Thorne as recommended by the natural dr.

[chartist]

LAJ,

That is a fairly potent combination that should offer other health benefits too! Sometimes regular borax foot soaks can help speed the process. One tablespoon of borax for every cup of very warm water in the foot bath container. Borax is considered a broad spectrum antifungal. Dusting the inside of the shoes with borax that has been ground into a very fine powder is also helpful as the shoes can harbor fungus and continually reinfect.

Art

[LAJ12345 in reply to chartist]

Ok will try that. His nail has almost crumbled off and looks like it may be ok underneath. It has been like it for 20 years getting worse over time and treatment dr gave him about 6-7 years ago made him so sick he could not finish it. Might also be helping having our current strict diet for last 2 1/2 years,

[chartist in reply to LAJ12345]

Good luck with it and I hope the borax is helpful!

Art

[chartist]

Another new (April 2021) study abstract suggesting benefit from berberine for T2DM :

pubmed.ncbi.nlm.nih.gov/338...

This new study (March 2021) illustrates how Berberine may also be useful for cardiovascular disease (CVD) :

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

In another new (March 2021) study abstract of an RCT, Berberine (900 mg/day) is shown to have the following effects in humans with schizophrenia :

Significant declines in total cholesterol, LDL cholesterol, fasting serum insulin and insulin resistance compared to placebo :

pubmed.ncbi.nlm.nih.gov/338...

Art

[chartist]

Berberine alone is useful in the fight against diabetes type 2 (T2DM), but the addition of melatonin may make it significantly better. As discussed in the original post, berberine is helpful for treating T2DM once you have it and melatonin is showing the ability to ameliorate many of the preexisting parameters that contribute to the potential to get T2DM in the first place which means the two together are likely to have synergy. Here is an interesting new study where they used 250 mg/day of melatonin in T2DM patients for just 8 weeks and saw significant improvements in factors that are known to contribute to getting T2DM, one factor of which, is obesity :

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

Art

[Fumaniron]

Great info. Wasn’t there a South Korean mouse study around 2012 that suggested dopamine neuron degeneration on berberine (that wasn’t reproducible I think). I believe I read that on one of the recent threads. I could be wrong…I’ve seen nothing but positive attributes regarding berberine since then

[chartist in reply to Fumaniron]

Fumaniron,

I haven't seen anything negative on Berberine for PD, only positive studies such as this newer one suggesting that berberine increases brain dopamine levels which sounds ideal to go with Albert's protocol or melatonin or possibly to help even out dopamine brain levels in PwP if it can be timed to coincide with off times, but that would take some trial and error to fine tune. I guess a simple starting point could possibly be taking berberine about an hour before a normal off time would normally begin and see if it can extend an on time. Once that has been adjusted and established probably see if it can extend the on time and possibly stretch out the next dose of C/L and so forth. When it comes to these type of things, we are pretty much on our own.

nature.com/articles/s41392-...

Art

[Fumaniron in reply to chartist]

Thanks, Art. That’s a great, updated study you provided, which gives me more confidence with use of berberine. I found the studies I mentioned early in this link. scienceofparkinsons.com/201... You have to scroll towards the bottom to see the pertinent 2 studies. I agree that those were the only potential negatives that I saw, and I am certainly open to your thoughts on them. Thanks again

[chartist in reply to Fumaniron]

Fumaniron,

I found one of the studies and they used either 5 mg/kg or 15 mg/kg in the rats. This approximately translates in an 80 kilogram person to 64 mg/day or 194/mg day which is very significantly lower than the recommended dosing for berberine in humans for use in diabetic patients of 1,500 mg/day.

In other studies I have seen where dosing that is too low or too high can have an opposite effect to what the optimal dose can have and this may be the case in this study. The other obvious issue is that rat studies do not always translate to human equivalency.

In the study I linked to, they were saying that berberine works by altering the gut biome activity to increase L-dopa production in the gut to be transported to the brain and then converted to dopamine. This may explain the problem right there. The dosing in the old study was delivered intraperitoneally, which means that the dosing bypassed the gut and in so doing, the benefit of increased gut production of levodopa was circumvented, hence they did not get the benefit of increased levodopa production in the gut which would have been transported to the brain and converted to dopamine!

That could clearly be the explanation for the discrepancy. That study was done in 2013 and I would have to do further research to get an idea about what was known about berberine back then. If a study was done like that today, I would expect that they would use a rat equivalent dose to the dose used for diabetes in humans and they would introduce it orally as in humans to get the increased levodopa production in the gut as seen in humans. I would say that this is the reason for the bad results reported in that study. In 2013 they probably had no clue that berberine had these levodopa increasing effects in the gut and so they thought intraperitoneal delivery would probably give more consistent effects than orally and they were right, but not in a good way!

The other study I could not find, but if it was an older study like the one I accessed, it could easily be the same issue.

It may be that all of the good that berberine does is done in the gut and delivery to other areas of the body such as the peritoneum may actually have negative effects, especially in rats!

Art

[Fumaniron in reply to chartist]

Thanks, Art! That explanation of using the gut in the studies to achieve the benefits makes a lot of sense. Another free, viewable study from the link I sent earlier would have likely had much better results if they administered orally, as well. Here’s the link to that 2014 study ncbi.nlm.nih.gov/pmc/articl.... Thanks for the eye-opener regarding route of administration affecting outcome!

[chartist in reply to Fumaniron]

Fumaniron,

In the study that you linked to, they used cells from rat's and exposed the cells to berberine directly. This goes back to what I was saying about the possibility that all of the reported benefits of berberine may be taking place in the gut and this study seems to add a bit of confirmation to that idea. If just 1 uM of berberine has a negative impact on the cells, then berberine may be creating its human benefits, not through direct contact with remote cells, but rather through an indirect method such as gut microbiome manipulation.

Many newer studies suggest that multiple health problems originate in the gut and this is a concept not lost on PD as the gut brain axis seems to be mentioned more and more in many studies. If perturbances in the gut can cause problems in other areas of the body, then it seems plausible that improvements to the gut microbiome can cause improvements in other areas of the body such as the brain, and the newer study that I linked to seems to confirm this idea as oral berberine caused increased dopamine in the brain. Other studies using probiotics, prebiotics, synbiotics, fermented foods and drinks etc. also add further confirmation to that whole idea of "improve the gut microbiome" and improve the health of the body. Many PwP are known to exhibit gut problems such as constipation well before they are ever diagnosed, so gut biome perturbence is showing before the disease symptoms in many cases. Animal studies have already shown that improving the gut microbiome can improve PD symptoms in animal models and doing a fecal transplant from an animal model of PD to a healthy control animal will cause the healthy control to start to get symptoms of Parkinson's.

The data is there to suggest that improving the gut microbiome of PwP can improve disease symptoms, but quality studies are lacking in PwP to date on this topic. A healthy gut biome is a healthful thing to work toward imo. Fecal transplants are currently the fastest way to do this, but in some instances have created new health problems, so there is still work to be done in this area of fecal microbiome transplants.

My thinking is that probiotics and synbiotics can improve the gut microbiome, but the dosing used in studies is generally to small to be maximally effective.

Art

[Fumaniron in reply to chartist]

Agree 100% with you, Art. Thank you for the insightful discussion!

[Hidden in reply to chartist]

What I don’t understand is, does berberine help protect the remaining neurons or is the increased dopamine production just addressing symptoms giving the impression of improvement while the cell death is not actually slowed? I fell down this rabbit hole when researching Exenatide which led me to metformin and now berberine.

[chartist in reply to Hidden]

ccl,

The one that does protect the dopaminergic neurons and mitochondria is melatonin. There is a reason that melatonin is produced directly in the mitochondria and can easily pass through the BBB while also having metabolites that have shown the ability to repair a compromised BBB. Melatonin is a natural repair molecule produced in the body for the body via melatonin receptors found throughout the body! The body can create its own melatonin via the pineal gland and short chain fatty acids in the gut! Melatonin production declines with age and with this decline comes the advancement of age related diseases of which PD is one. Boost Short Chain Fatty Acid (SCFA) producing bacteria in the gut along with fermentable fiber and prebiotics and you increase SCFAs which then increase melatonin and its receptors which then increase SCFA producing bacteria which interacts with the prebiotics and fermentable fiber which then increase SCFAs which then produce more melatonin in a continuous repetitive healthful cycle. I'm going to stop here because I am blue in the face. 😅😅😅

Art

[chartist]

This 2020 systematic review suggests that Berberine may be useful in delaying or preventing dementia and cognitive issues in T2DM patients :

pubmed.ncbi.nlm.nih.gov/320...

Here is a copy of the conclusion :

>>> ' Conclusion: Berberine could impede the development of dementia via multiple mechanisms: preventing brain damages and enhancing cognition directly in the brain, and indirectly through alleviating risk factors such as metabolic dysfunction, and cardiovascular, kidney and liver diseases. This study provided evidence to support the value of berberine in the prevention of dementia associated with MetS. ' <<<

Art

[Kwinholt]

Art, Thank you for all that information, my head is soaking it all in. I have a niece and nephew,(on my husbands side) that are both T1 diabetics on insulin pumps. I should tell them to hook me up!! Just a joke. They inherited it from their dad who was Type 1 as well, but has passed away from his. The protocol has advanced for Type 1 but you always need to stay on your game. Thank you for the info. Karen

[chartist]

Karen,

T1D has shown that gut dysbiosis is a feature of the disease, similarly to PD. Association does not equal causation, however FMT in T1D has shown improvement as described here :

gut.bmj.com/content/70/1/92

I had a friend who died from T1D when I was much younger and he literally went in pieces as they cut him up like a car in a junkyard until he was no more. It is a horrible disease! Given the results of this link above, I would look into what I have been talking about in recent posts regarding manipulating the gut microbiome until such time as FMT M-I-G-H-T become available.

Art

[Bolt_Upright]

These seem troubling to me...

scienceofparkinsons.com/201...

Bad results:

Title: Effects of berberine on 6-hydroxydopamine-induced neurotoxicity in PC12 cells and a rat model of Parkinson’s disease

Authors: Kwon IH, Choi HS, Shin KS, Lee BK, Lee CK, Hwang BY, Lim SC, Lee MK.

Journal: Neurosci Lett. 2010 Dec 3;486(1):29-33.

PMID: 20851167

In this study, the investigators found that berberine was having a toxic effect in models of Parkinson’s disease, both cell-culture and rodent models. The researchers treated the rats with berberine once daily for 21 days, and they found a marked reduction in the number of dopamine neurons in the substantia nigra when compared to Parkinsonian rats that did not recieve berberine.

Bad results:

Title: Neurotoxic effects of berberine on long-term L-DOPA administration in 6-hydroxydopamine-lesioned rat model of Parkinson’s disease.

Authors: Shin KS, Choi HS, Zhao TT, Suh KH, Kwon IH, Choi SO, Lee MK.

Journal: Arch Pharm Res. 2013 Jun;36(6):759-67.

PMID: 23539311

In this follow-up study, the researchers repeated their previous study with the difference of including Levodopa treatment to determine if this made any difference in the outcome. The investigators modelled Parkinson’s disease in rats and then treated them with berberine and/or Levodopa once daily for 21 days. Again the researchers found that berberine administration to neurotoxin treated animals exaggerated dopamine cell loss when compared to the neurotoxin treated control animals, but with the addition of Levodopa to berberine treatment, the loss of dopamine neurons was made worse.

Good results:

Title: Berberine protects 6-hydroxydopamine-induced human dopaminergic neuronal cell death through the induction of heme oxygenase-1.

Authors: Bae J, Lee D, Kim YK, Gil M, Lee JY, Lee KJ.

Journal: Mol Cells. 2013 Feb;35(2):151-7.

PMID: 23329300 (This article is OPEN ACCESS if you would like to read it)

In this study, the investigators pretreated cells in culture with berberine before exposing them to a neurotoxin (6-OHDA) and they found significantly better survival of cells in the berberine treated group. They found that the positive effect was partly due to the an increase in a protein called heme oxygenase 1 (HO-1), which is known to protect dopaminergic neurons against neurotoxicity (Click here for more on this).

Good resoults:

Title: Berberine prevents nigrostriatal dopaminergic neuronal loss and suppresses hippocampal apoptosis in mice with Parkinson’s disease.

Authors: Kim M, Cho KH, Shin MS, Lee JM, Cho HS, Kim CJ, Shin DH, Yang HJ.

Journal: Int J Mol Med. 2014 Apr;33(4):870-8.

PMID: 24535622

The mice in this study were orally administered berberine once a day for a total of 5 weeks, and the researchers found that treatment with berberine enhanced motor skills and coordination by preventing dopamine neuron loss and damage. They concluded that “Based on these data, treatment with berberine may serve as a potential therapeutic strategy for the alleviation of memory impairment and motor dysfunction in patients with Parkinson’s disease”.

Bad results:

Title: Mitochondria and NMDA receptor-dependent toxicity of berberine sensitizes neurons to glutamate and rotenone injury.

Authors: Kysenius K, Brunello CA, Huttunen HJ.

Journal: PLoS One. 2014 Sep 5;9(9):e107129.

PMID: 25192195 (This article is OPEN ACCESS if you would like to read it)

In this study, the investigators looked at what berberine does inside cells and they found that berberine causes rapid mitochondria-dependent toxicity in neurons, characterised by mitochondrial swelling and dysfunction.

[chartist in reply to Bolt_Upright]

I've already explained the reason for the bad results higher up in this thread. If you read the studies you'll understand why.

Art

[Bolt_Upright]

Found My Fitness Berberine

foundmyfitness.com/topics/b...

[chartist]

It appears that melatonin is right here knocking on Berberine's door asking to lend a hand in the fight against diabetes type 2 (T2DM)! The following study shows how high dose melatonin (250 mg/day) is useful in fighting off the negative cardiovascular effects of T2DM as well as fighting some of the causes of T2DM:

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

This new (September 2021) meta analysis of melatonin for T2DM also illustrates the value of melatonin in the fight against T2DM :

pubmed.ncbi.nlm.nih.gov/344...

Of course both are considered very useful in CVD prevention and treatment . The following study illustrates the usefulness of Berberine in CVD :

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

The following gives many examples of the value of Melatonin as a preventative and treatment of CVD :

healthunlocked.com/cure-par...

Lastly, but also very importantly, these two are both useful for Parkinson's Disease as I have already written about!

Art

[Despe]

Art,

I am considering of having hubby try Berberine but he is not diabetic nor pre-diabetic, no cholesterol nor heart issues and he certainly doesn't need to lose weight. Is it still safe to start him on low dose Berberine? I have read a lot of information on Berberine, and I trying to weigh its benefits vs side effects. Thank you!

[chartist in reply to Despe]

What benefits are you trying to achieve for your husband, Despe? The Berberine is a healthful supplement as is Citicoline and both are noted for their anti dementia effects and both are noted for increasing dopamine in the brain.

Art

[Despe in reply to chartist]

Thanks, Art! You gave me the answer. He is on Citicoline already, add Berberine then? My question basically is "Would it affect his weight, his glycemic index?"

[chartist]

It likely will have a minor effect on weight loss, so I wouldn't let that be a deciding factor. You know this stuff always comes down to trial and error, Despe!

Art

[chartist]

This new meta analysis(MA) of RCTs( December 2021) of the use of Berberine for T2DM is very enlightening and clearly illustrates that Berberine is a very good adjunctive treatment or possibly even a primary treatment option for T2DM :

ncbi.nlm.nih.gov/labs/pmc/a...

Here is an important quote from the full MA :

>>> ' Forty-six trials were assessed. Analysis of berberine applied alone or with standard diabetic therapies versus the control group revealed significant reductions in HbA1c (MD = −0.73; 95% CI (−0.97, −0.51)), FPG (MD = −0.86, 95% CI (−1.10, −0.62)), and 2hPG (MD = −1.26, 95% CI (−1.64, −0.89)). Improved insulin resistance was assessed by lowering FINS (MD = −2.05, 95% CI (−2.62, −1.48)), HOMA-IR (MD = −0.71, 95% CI (−1.03, −0.39)), and BMI (MD = −1.07, 95% CI (−1.76, −0.37)). Lipid metabolisms were also ameliorated via the reduction of TG (MD = −0.5, 95% CI (−0.61, −0.39)), TC (MD = 0.64, 95% CI (−0.78, −0.49)), and LDL (MD = 0.86, 95% CI (−1.06, −0.65)) and the upregulation of HDL (MD = 0.17, 95% CI (0.09, 0.25)). Additionally, berberine improved the inflammation factor. ' <<<

This multitude of positive heath enhancements including reduction of inflammatory mediators IL-6 and Tnf-alpha as well as positive heart and kidney effects accompanied by a very good safety profile make Berberine a "must consider" option for people with diabetes. The added lipid improving effects are just the icing on the cake.

It seems likely that pulsing of Berberine dosing may prolong the effectiveness of Berberine over the longer term, helping to prevent the body from becoming resistant to its effectiveness.

Art

[chartist]

I thought it is a good time to update this thread with this new study (May 2022) of berberine use in people with PD. This study showed that berberine significantly lowered inflammatory markers IL-6, IL-8 and TNF-alpha. It further showed that berberine also helped to improve the perturbed gut microbiome. Interestingly, they only used 200 mg of berberine given 3 times per day for a total of 600 mg/day for 3 months.

hindawi.com/journals/cmmi/2...

Here is a relevant quote from the study :

>>> ' In summary, berberine hydrochloride can suppress the expression of inflammatory factors in PD patients and improve the disorder of intestinal flora. Since the PD intestinal flora may promote the occurrence of misfolding of α-synuclein, the study concerning the PD intestinal flora and inflammatory cytokines may further supplement the therapeutic mechanism of berberine hydrochloride. ' <<<

This study leaves me with the burning question of whether a higher berberine dose would have fully normalized the gut biome of the PD study participants. In diabetic patients, 1500mg /day in 3 divided doses is considered to be near optimal with 2000 mg/day being the high end of supplementing in other studies, but this study only used 600 mg/day???

Art

[chartist]

To further highlight and update the use of Berberine in T2DM & PD this new (February 2023) systematic review and meta analysis (link below) makes a very important point. In both PD and T2DM, cardiovascular disease (CVD) is at increased levels and this meta analysis suggests that Berberine is also quite useful in the fight against CVD.

pubmed.ncbi.nlm.nih.gov/368...

A couple of relevant quotes from this meta analysis :

' Berberine alone significantly reduced National Institute of Health Stroke Scale (NIHSS) score, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intima-media thickness (IMT) levels than routine therapy. '

' This study suggests that berberine may be a promising alternative for CVDs with no serious adverse reactions. '

Art