Metformin Causes Cell Death, Increases Risk for Alzheimer’s Disease

Monday, December 05, 2016
By: Linda J. Dobberstein, Chiropractor, Board Certified in Clinical Nutrition

The blockbuster drug, metformin, is considered effective, safe and cost-effective for priority conditions and a basic healthcare system. It is the most widely used medication for type 2 diabetes. While this drug was discovered nearly 100 years ago and considered safe and essential to medicine, recent research may turn this belief upside down. It should make you stop and think about that seemingly harmless drug and the subtle memory and cognitive changes that are attributed to normal aging.

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Metformin, a generic type 2 diabetes drug, and its brand name equivalents - Fortamet, Glucophage, Glucophage XR, Glumetza, and Riomet has at least three known adverse consequences. One is the well-known issue that metformin interferes with and depletes vitamin B12 and folate and raises homocysteine levels. This finding alone is enough to make this drug worrisome for anyone with methylation concerns, seniors, digestive concerns, or gastric bypass patients as these are commonly related with vitamin B12 and folate deficiency. The second concern is the build-up of lactic acidLactic acid can make muscles hurt, markedly increase fatigue and rarely be deadly. It reflects an insult to normal metabolism and aerobic energy production. The third recently discovered issue is piercing its way through medical research and raises serious concerns about metformin.

Metformin Causes Mitochondrial Dysfunction and Nerve Cell Death

Research published in the journal Aging, August 2016 is the latest article in a progression of cellular and animal studies that demonstrates increased risk of Alzheimer’s with chronic use of metformin. Metformin induces mitochondrial dysfunction and cell death in the brain by affecting several proteins, including beta-amyloid protein. These issues lead to build-up and aggregation of beta-amyloid and to an overall increase risk of Alzheimer’s disease onset.

Ten years ago, scientists looked at how mitochondrial dysfunction occurred in Alzheimer’s disease. They looked at a compound called amyloid precursor protein (APP) and how it was “gumming up” protein moving channels in the brain’s mitochondria. Certain parts of the brain, like the frontal cortex (cognition, behavior, learning, memory), hippocampus (emotion, memory, and autonomic nervous system) and amygdala (emotions) had higher levels of APP when Alzheimer’s disease was present. Nerve tissue associated with acetylcholine, dopamine, GABA, and glutamate neurotransmitters also had high levels of APP accumulation. Researchers felt that the abnormal accumulation of APP in the mitochondria and nervous system is a “hallmark of human Alzheimer’s disease pathology.”

Researchers found similar accumulation and production of APP and beta-amyloid proteins in cells exposed to metformin/GlucophageR leading to the classic changes seen with Alzheimer’s disease pathology. Scientists viewed this as an increased risk for Alzheimer’s development and consequence of metformin use especially when used as a monotherapy in elderly diabetic patients. The act of blindly prescribing this drug to borderline situations or the elderly is not as benign as once believed.

Cellular studies demonstrate the depth of metformin’s adverse cellular effects. Metformin increases APP and another protein, presenilin, which are both involved in Alzheimer’s disease. These two proteins promote the aggregation of beta-amyloid. In these studies, it was also shown to cause oxidative stress, mitochondrial damage, and decrease production of two key enzymes essential for mitochondrial function and blood sugar function. Metformin hampers the natural cellular clean-up and structural preservation of brain mitochondria. It blocks the exchange of molecules in cell fluid and mitochondria. The end result of these changes is cell death. Metformin to mitochondria is like spark plugs wearing out on the car and slowly dumping sand in the engine. The adverse effects don’t happen overnight, but over time, it provokes accumulating damage. 

Metformin also decreases activity of an essential antioxidant pathway regulator, Nrf2 and decreases production of brain repair compounds like BDNF and Nerve Growth Factor. Nrf2 is part of a major mechanism that provides cellular defense against oxidative stress and electron activity wear and tear.  A lack of Nrf2 activity leads to higher levels of free radicals and decreased antioxidants within the nervous system and elsewhere in the body. These brain changes caused researchers to conservatively state “The decrease in neurotrophic factors (BDNF, etc) and Nrf2 with chronic metformin intake, cautions of the possibility that extended metformin use may alter brain biochemistry in a manner that creates a vulnerable brain environment and warrants further investigation.”

Metformin for All?

Metformin is not just used for type 2 diabetes management. It is also used in cancer and weight loss treatments. It has been heralded as a drug for reducing cancer risks, heart disease, weight loss, children, and pregnant women too, almost taking it to the point that metformin should be used by all. Does this remind you of the statin drug push, where some experts wanted to put it in drinking water as prevention for all?

Controversy exists with metformin use. Many proclaim its benefit for diabetes and reducing complications. Indeed, other studies cite reduced risk for Alzheimer’s disease with metformin treatment with a focus on different aspects of physiology. Clearly, this is a tangled web of information with the addition of this newest research. But, where there is smoke there is fire. The rate at which diabetes is increasing and the rate at which Alzheimer’s is occurring is certainly linked together. Is this drug contributing to the devastating effects of beta-amyloid plaques in ways previously not understood? It’s time to re-evaluate. It is time to take charge of your health.

Prevention and Addressing the Consequences of Metformin Use

There are different ways to prevent and manage this conundrum. Ideally, prevention, healthy diet and lifestyle is the foundation to stopping type 2 diabetes.  However, for those who take metformin, there are key factors that can be employed to offset the duress.

Drug-Depleted Nutrients

Drug-nutrient depletions should never be ignored. The British Medical Journal tackled the issue of metformin’s effect on vitamin B12 and homocysteine. Results showed an average 19 percent decrease in vitamin B12 levels and an elevated homocysteine level average of 23.7 µmol/. Ideal homocysteine levels are 7.2 and less. Metformin users were found to need intervention to replenish vitamin B12 levels. The negative impact on vitamin B12 and homocysteine worsens the longer the drug is used. 

Healthy Management of Insulin, Blood Sugar, and Leptin

Insulin plays a protective role against metformin, preventing the build-up of amyloid proteins and mitochondrial destruction. One of the things that occurs with type 2 medications like metformin is that they lower blood sugar, often to the point of hypoglycemia, creating yet another stress response on the brain. At the same time, insulin resistance and leptin resistance are significant factors in the type 2 diabetes problem. In some studies, scientists recommend using prescription insulin with metformin to off-set the damage from metformin. In managing health, it makes more sense to manage the insulin and leptin hormones that are already present, but working inefficiently. For a very thorough description of this, read the newsletter – Insulin, Leptin, and Blood Sugar – Why Diabetic Medication Fail. Dumping more insulin into the picture, when already insulin resistant, may attenuate the metformin adverse effects, but a better strategy is using the hormone already there in a healthier manner. Several nutrients help support insulin function. These include cinnamon, chromium, vanadium, bitter melon, gymnema sylvestre, grape seed extract, omega-3 fish oils, and others. Nutrients like PQQ, coenzyme Q 10, and magnesium help to buffer and manage lactic acid.

Antioxidants Protect Against Metformin Adverse Effects

In addition to the balance and healthy function of insulin, antioxidants offset metformin’s adverse effects. Curcumin and ferulic acid have received honorable mentions. Ferulic acid is found in cell walls of plants, thus found in grains, fruits, and vegetables. Some of the foods with the highest content include bamboo shoots, red beets, peanuts, spinach, grapefruit, oranges, banana, whole grain rye and oats, coffee, cinnamon, curcumin, and more.

Several other nutrients also provide great benefit and are heralded as go-to nutrients for these concerns. Nobiletin, a flavonoid from citrus fruit, demonstrates positive effects on protecting cognitive function and preventing beta-amyloid build-up. It also provides a substantial impact in managing obesity and metabolic syndrome.

Resveratrol and vitamin D combined improve nerve degeneration and insulin function. EGCG, the active ingredient in green tea extract, melatonin, resveratrol, and vitamin B12 caused a significant reduction in beta-amyloid proteins, pro-inflammatory proteins, and reactive oxygen species (ROS) and an improvement in antioxidant enzymes in Alzheimer’s disease cells.  The combination of antioxidants together delivered a much greater benefit than the individual nutrients. The Journal of Alzheimer’s Disease November 2016 publication found that using this “novel therapeutic approach to address a currently unmet medical need, would benefit not only Alzheimer’s disease patients and their caregivers, but also society as a whole.” It is refreshing to hear this stance, given the desire by many to give metformin to nearly anyone.

There is certainly a need to manage type 2 diabetes, as it is a massive epidemic in industrialized countries world-wide. Type 2 diabetes, obesity, and metabolic syndrome increase the risk for Alzheimer’s disease. However, the approach of driving down blood sugar numbers and managing these conditions with metformin leads to mitochondria and nerve cell death and makes little sense. Discuss different options with your medical provider if you must be on some type of medication.

Drugs were never meant to take the place of good choices. It is vital for you to ensure a nutrient dense, antioxidant rich diet with many servings of brightly colored fruits and vegetables each day. It is critical to restore vitamin B12 and folate levels due to drug-nutrient depletions. It is just as imperative to utilize antioxidants to protect mitochondria from toxic drug damage. Focus on a variety of different antioxidants as this creates a synergistic effect. Numerous nutritional compounds, in addition to what was discussed above, are known to support and even regenerate mitochondria. These include NAC, acetyl-l-carnitine, lipoic acid, PQQ, coenzyme Q10, tocotrienols, B vitamins, arginine, grape seed extract, magnesium, and more. Watching your loved one on metformin with diabetes lose their memory and themselves is heart wrenching. Knowledge is power to change life and destiny. Prevention is key, but even with active health concerns, positive health benefits can occur with the right support. Don’t wait before it is too late!

Nutritional Options

Curcumin - Curcumin is the work-horse of antioxidants. It provides incredible support for inflammation management throughout the body, but especially the brain. This spicy antioxidant helps reduce cancer risk, protects mitochondria, helps weight loss and blood sugar management. Standardized extracts combined together with bioperine, a black pepper extract, provides excellent quality and absorption.

Nobiletin – This flavonoid from obtained citrus fruit, protects cognitive function and is shown to help prevent beta-amyloid build-up. It is used to manage obesity and metabolic syndrome. It is a potent antioxidant with protecting against neurological inflammation and considered a premiere anti-aging nutrient.

Vitamin B12 – Several drugs, digestive concerns, and other factors deplete and rob the body of vitamin B12. All Wellness Resources vitamin B12 containing products offer it in the preferred coenzyme form that addresses methylation difficulties and homocysteine build-up.

EGCG – This green tea extract antioxidant provides several different benefits. It protects nerve tissue, mitochondria, and quenches free radicals. It also benefits healthy metabolism, weight, blood sugar, blood pressure, and fatty liver difficulties – all concerns associated with type 2 diabetes. Cheap green tea is often contaminated with pesticides, heavy metals, and other pollutant. We offer only a highly purified, highest quality green tea extract available on the market.

PQQ – PQQ is a super antioxidant that is prized for its role in making new mitochondria. PQQ protects mitochondria too. It has been shown to help remove lactic acid build-up and reduce inflammation in the brain, heart, thyroid, immune system and elsewhere.

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