metformin

Metformin: Medical Marvel or Magical Medicine?

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I am not a big fan of metformin (Glucophage). My disdain for metformin stems not from its efficacy. Metformin is quite adept at lowering blood sugar. In that sense, it is a medical marvel. Consider a pill that will ensure that no matter the individual’s intake of sugar, blood glucose measurements will magically fall within a normal range. What a wonderful invention – to have one’s cake, eat it too, and all the while, maintain normal blood sugar – who wouldn’t want that?

Alas, however, like all magic tricks, when the sleight of hand is revealed, the luster is lost. In the case of metformin, the underlying prestidigitation is not so magical after all. Metformin, like other wonder drugs, treats a symptom of a much greater problem; a symptom that in reality is just a visible sign of a necessary and protective innate process designed for cellular survival. The symptom is insulin resistance, the problem is too much dietary sugar and too few nutrients – an insidious form of high-calorie malnutrition that at once overloads cellular and mitochondrial processing capacities and starves the cells of critical nutrients.

Nutrients – They’re Necessary

A little-appreciated fact in modern medicine, vitamins and minerals power all of the machinery involved in cell function and in mitochondrial energy production. No nutrients, no energy, cellular starvation (even in the face of weight gain), inflammation, dysfunction, and ultimately, death. In the face of too much sugar and not enough nutrition, insulin resistance seems perfectly logical. If cellular fuel is waning, why not keep a little extra floating around, but since the apparatus to process said sugars is crippled, we have to turn down the intake valves. I would argue that it’s not obesity causing insulin resistance, after all not all overweight folks have type 2 diabetes, and not all insulin-resistant diabetics are overweight. It’s the damned sugar and lack of other nutrients initiating insulin resistance. Both the insulin resistance and fat storage are survival mechanisms; ones that ultimately have pathological consequences, but survival mechanisms nevertheless. In fact, folks who are diabetic and overweight have a lower all-cause mortality rate than those who are diabetic and thin.

If the problem is high-calorie malnutrition, which manifests as elevated blood sugar and in many cases, increased fat storage, wouldn’t the more prudent solution be to rectify the problem, to cease sugar intake, and address the nutrient deficiency? Wouldn’t that unwind the damage and heal the body? I think so, but alas, that’s not what we do in modern medicine. No, we don’t correct the problem, we treat the symptom(s) and then we revel in all the cool mechanisms we can interrupt, never considering the bigger picture.

Metformin Usurps Cell Signaling

Metformin bypasses our cells’ innate response to too much of anything – downregulation or desensitization – by overriding the communication systems that control these functions. In this case, metformin becomes the signaling molecule that tells the liver if and when to release glucose into the bloodstream. From an engineering standpoint, it’s a fantastic workaround. No need to address the core problem, just rewire the communication and continue on as if nothing is wrong. The added bonus is that for all intents and purposes, it works. Blood sugar declines, as does some of the pathology associated with elevated blood sugar. A medical marvel, right?

Well, not so fast. It just so happens that we need those pesky nutrients to function and to survive. When we give metformin to individuals who are already in a state of malnutrition, we are effectively ignoring and extending the underlying deficiencies that initiated the insulin resistance in the first place. More importantly, and this is something that is missed almost entirely in western medicine, we are adding to the metabolic mess a chemical that directly leaches a whole bunch of nutrients on its own (which further disables cell function, increases insulin resistance, increases fat storage in the long term and all of the associated pathologies we have come to know and love). Furthermore, we’re disrupting energy metabolism – energy that all cells need to function – and while that may quell some pathologies in the short term, in the long term, we’re all but guaranteeing a progressive decline into ill-health, despite the cheerleading that suggests otherwise.

We Get It. Metformin Treats a Symptom Not the Root Cause. So What?

Why am I blustering on about metformin now, when I have done so on several occasions previously (here, here, and here)? Well, an emerging body of research is showing yet another set of mechanisms by which metformin derails health. It turns out, that in addition to depleting vitamins B12 and B9, which are responsible for 100s of enzymatic reactions and particularly important in central nervous system function including myelination (how many cases of diabetic neuropathy or multiple sclerosis are really vitamin b12 deficiency?) and tanking CoEnzyme Q10 which effectively cripples mitochondrial ATP production in muscles (and likely exercise capabilities) with the resultant loss inducing a whole host of pathological processes (muscle weakness, cognitive decline among a few), metformin also blocks vitamin B1 – thiamine – uptake by multiple mechanisms. And for kicks and giggles, it appears to interfere with the body’s innate toxicant metabolism pathways, the P450 enzymes, rendering those who use this drug less capable of effectively metabolizing a whole host of other medications and environmental toxicants.

Thiamine is Critically Important to Health

For those of you who don’t read our blog and/or are not familiar with thiamine and thiamine deficiency, let’s just say, thiamine is the granddaddy of nutrients, an essential cofactor at the top of the fuel processing pyramid. Without thiamine, food fuel from carbs and, to a lesser extent, fats cannot be converted into ATP. With declining fuel sources, mitochondrial functioning degrades as well and all sorts of diseases processes ensue.

Sit with that for a moment. We’re giving folks who already have an issue with converting foods to energy and who are already very likely nutrient deficient, a medication that blocks the very first step in that conversion process. Since metformin also blocks the lactate pathway and acetyl-coenzyme A carboxylase (an enzyme necessary to process fatty acids into fuels), blocking thiamine effectively shunts the mitochondrial input pathways. Mind you, this is in addition to blocking the critical electron transport functions – via CoQ10 – found at the back of ATP processing. Talk about an induction of energetic stress.

So What If a Few Vitamins Are Depleted?

I bet you’re thinking if these nutrients are so important and metformin is so dangerous, why isn’t metformin more toxic? After all, metformin has been on the market for over 50 years, is considered the first line of treatment for type 2 diabetes, and just about every research article published on this drug begins with a blanket statement that metformin has an excellent safety record.

Why, indeed? Let us consider what constitutes a safe drug?

In modern medicine, the notion of drug safety and toxicology are equated with acute reactions. For decades, we have been operating under the false assumption in medical and environmental toxicology that if something doesn’t kill us immediately it must be safe (and the equally false assumption that toxicological responses are necessarily linear). Many drugs (and environmental toxicants) are much more subtle in their damage. They disrupt systems that, in many cases, have the capacity to compensate, at least for a period of time and until a critical threshold is met. Mitochondrial energetics is one of those systems that is remarkably resilient in the face of a myriad of stressors, sometimes taking years for the damage to be recognized. With nutrient deficiencies, in particular, compensation is aided by continuously changing environmental and lifestyle considerations. Sometimes we eat very well and other times we don’t; sometimes life is good, other times, it is not. Stressors vary.

Nutrient Deficiencies Wax and Wane

With nutrients deficiencies, especially essential nutrients that require dietary intake, there can be waxing and waning of the symptoms that these deficits evoke as diet and other variables change. It’s not until one reaches a critical threshold that the deficiency is recognized if it is recognized at all. With thiamine deficiency, in particular, animal research suggests the threshold for severe symptoms may be as high as 80% depletion. Imagine a system that can maintain life in the face of up to an 80% deficiency. That is remarkable.

Symptoms of severe thiamine deficiency include those associated with a condition called Wernicke’s Encephalopathy, a serious and potentially fatal medical emergency with neurological and cognitive impairments, oculomotor and gait disturbances, and cardiac instability. With milder deficiencies, however, we see things like fatigue, muscle pain, mental fuzziness, GI disturbances, autonomic dysregulation, and a host of symptoms that can easily and incorrectly be attributed to other conditions and/or modern life in general.

Interestingly, once thiamine depletion reaches that critical threshold, it doesn’t take much thiamine to begin seeing improvement in the symptoms. In those same animal studies mentioned above, it took an increase of only 6% of the total thiamine concentration to begin the improvement. So with a change from 20 to 26% of recommended thiamine concentration, symptoms begin to dissipate, at least temporarily. Sit with than one for a moment – what a remarkable bit of resilience. It takes a full 80% reduction in thiamine stores before serious symptoms are recognized but improvement begins with only an additional 6% – when the system is still depleted by 74%.

Given the metabolic capacity to maintain survival in the face of all but critical deficiencies, it is easy to see how and why blocking these nutrients would not be considered dangerous or at least obviously so. The decline is so gradual in most cases, and likely waxes and wanes, that it becomes near impossible to attribute symptoms and underlying nutrient deficiencies to the offending medication(s). Unfortunately, just because we don’t recognize those patterns, doesn’t mean that they do not exist.

How Metformin Blocks Thiamine: The Technicals

Backing up just a bit, it is important to understand the mechanisms by which metformin reduces thiamine. When metformin is present, a set of transporters that normally bring thiamine into the cell to perform its task as a cofactor in the machinery that converts carbs to ATP, brings metformin into the cell instead, replacing thiamine altogether. The transporters involved are the SLC22A1, also called the organic cation transporter 1, [OAT1], and the SLC19A3. Conversely, when metformin is not present or at least not overwhelming all of the transporters as it is during the initial phases of absorption post intake, thiamine becomes available for transport. Since these transporters are not completely and continuously blocked (and there are other thiamine transporters), thiamine uptake occurs, just not continuously and just not at full capacity. This may be one reason why metformin is not as acutely damaging as some of the other drugs in its class, but make no mistake, it is still dangerous. Thiamine deficiency is deadly. With the right combination of thiamine blocking variables (other medications/vaccines block thiamine as well), thiamine concentrations can tank and even if the thiamine concentrations hover at a subclinical deficit, the likelihood of chronic illness is high.

Thiamine and Diabetes: Connecting a Few More Dots

A little over a year ago, I stumbled upon some research showing a high rate of thiamine deficiency in individuals with both type 1 and type 2 diabetes (75% and 64%, respectively). I wrote about that research in Diabetes and Thiamine: A Novel Treatment Opportunity. According to several studies, diabetics appear to excrete higher amounts of thiamine than non-diabetics. The research attributes this to either poor kidney reabsorption and/or mutations in the thiamine transporter genes that prevent absorption. None of the research detailed the medication usage of the participants, but one might expect a good percentage of the type 2 diabetics were using metformin. It seems reasonable that if metformin supplants thiamine uptake via the thiamine transporters mentioned above, then the body would excrete the unused thiamine, leading to a higher rate of thiamine excretion than observed in non-diabetics and a higher rate of thiamine deficiency in diabetics versus non-diabetics. Based upon this, additional clinical research has shown that thiamine supplementation normalizes, the aberrant processes activated by sustained hyperglycemia including:

Metformin, in treating a symptom rather than a root cause, is likely exacerbating, and perhaps even initiating, some of the very disease processes that it is intended to prevent. Although metformin is not often acutely toxic, the underlying mechanisms manipulated by this drug suggest that it is likely to induce and not prevent, as is so frequently suggested, chronic illness. From my perspective, that makes metformin a very dangerous drug.

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, and like it, please help support it. Contribute now.

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This article was published originally on Hormones Matter on February 16, 2016. 

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Unexplained New Onset Fatigue and Other Symptoms

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For almost a year, I have suffered from fatigue, morning sinus and congestion problems, and other health issues including type 2 diabetes, insomnia, and depression. For the last four months, I have been dealing with a skin rash on my legs, arms, stomach, and small outbreaks on my face. I have been misdiagnosed by my primary doctor and two different naturopaths. They told me that it was fungal and I was given anti-fungals. I don’t remember the name. After a second visit to a dermatologist, the doctor did a scraping and a biopsy and told me that it definitely wasn’t fungal. They are going to do some patch tests this week. I have had to keep my mental outlook positive because, for the last year, the doctors have had no answers.

My primary has told me that I am an anomaly. Great! But still no answers. She has done a plethora of blood tests, two or three CAT scans, and other imagery. The only blood test that was a little high was my white blood cell count. My iron is high because of my testosterone injections. I was initially told that I had Lyme’s disease but my blood tests found that to be negative. Then I was told that I have Epstein Barr, but my blood tests were negative for that also. I am used to an active lifestyle, lifting weights, hiking, backpacking, fishing, martial arts, etc., but, for the last year, I have been extremely low energy with significant fatigue. I will sleep 8 hours, get up for a while, and just feel like going back to bed. I would like my life back!

Early Thyroid Problems

I take levothyroxine because my thyroid was low about 20 years ago. They did a scan of my thyroid and told me that my thyroid was quite small, probably due to my Graves’ disease treatment when I was 16 years old. I was told that I was close to death at that time. I remember some of the unpleasant things I went through at that time. They gave me a drink called a “nuclear cocktail” and then, for the next 4+ years, they treated me with propylthiouracil. I fought my way through this disease and started lifting weights and working out when I felt better. I was about 16 years old at the time. I continued to work out and have been athletic all of my life.

Back Pain and Spine Curvature

After years of athletics that included snow skiing and martial arts, I began to develop significant back pain. After an MRI in 2004, the doctors asked if I had polio. The test showed curvature of the spine, a bulging disc, and some areas of bone on bone.  At that point, I was prescribed oxycodone and have been on it ever since. Despite the back issues, I have functioned fine until this last year when a variety of new symptoms manifested, including unremitting fatigue. I have had a big change in my energy levels, sex drive, and the pain issues have increased and so it is a struggle to lift weights. My hands, shoulders, spine, and feet have increased pain. I have always been very self-motivated, but this last year has been very tough. The doctors say that I have osteoarthritis and fibromyalgia. I don’t know anymore.

Maybe Thiamine for the Fatigue?

Recently, I listened to Elliot Overton’s interview with Dr. Marrs about thiamine and found many of my symptoms were possibly linked to thiamine deficiency. I have taken a myriad of nutritional supplements over the years. They are listed below. All to no avail. I have also started taking thiamine, but the jury is not out on that yet. It has been pretty expensive with all the doctor appointments and nutritional/medical expenses.

There is a lot more that I have probably missed, but I wanted to keep this to a short story, not a novel. What am I missing with my health issues? The fatigue is unending. The doctors have no advice and consider me an anomaly. Am I? Or are we simply missing something?

Current Medications

  • Levothyroxine-125mcg – for approximately 29 years.
  • Sertraline-50 mg – last two years
  • Lisinopril-10mg – last year and a half
  • Metformin-750mg – last two years
  • Hydroxyzine-50 mg – at bedtime for sleep issues for the last year and a half
  • Oxycodone-10 mg up to 4 times a day since 2004. I see my spine doc every 2 months. I have some spine damage and joint issues from the martial arts and various other sports.
  • Dicloflenac- 50 mg (Rarely use)
  • Lunesta-3 mg (1 at night) – this was given to wean me off of clonazepam.
  • Testosterone-.5 ml – injection every 2 weeks – for low testosterone
  • Aspirin-81 mg-one a day for thick blood due to the testosterone replacement therapy
  • Kenalog injection for rash. I have had only one injection and the dermatologist told me that it would be good for a month.
  • Triamcinolone cream to use on the various rash sites.

Current Supplements

  • Vitamin D3-10,000 IU a day (Kirkland brand)
  • B12-5000 mcg sublingual 1 a day
  • Saw Palmetto-450 mg, 1 a day (ZHOU brand)
  • Ceylon Cinnamon-1200 mg, 1 a day (Spring Valley brand)
  • Garlic-2 capsules, 1 a day (Kyolic brand)
  • Niacinamide-500 mg, 2 times a day (Nutricost)
  • Liposomal Vitamin C-1400 mg, twice a day
  • Benfotiamine-300 mg, twice a day

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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This article was published originally on February 19, 2020.

COVID Notes: Considering Drug Induced Mitochondrial Damage

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Much has been written about the associations between COVID severity, chronicity, and pre-existing conditions. Top among those conditions include cardiovascular disease and diabetes, likely type 2, but both are lumped together. What has not been discussed is why this would be the case. On a basic level, fighting two illnesses takes more energy than fighting one. This is obvious. What is not obvious is that many modern illnesses, especially cardiovascular disease and type 2 diabetes, begin in the mitochondria as a consequence of diet and lifestyle. Statistically, 80% of cardiovascular disease and 78-83% of type 2 diabetes can be traced back to longstanding dietary, lifestyle and environmental issues* that effectively diminish mitochondrial energetic capabilities and disrupt metabolic flexibility; and the remainder that did not originate from diet and lifestyle are certainly affected by these variables.

To function effectively and to convert the foods we eat into energy or ATP, the mitochondria require sufficient vitamins and minerals, 22 of them, in fact. Western diets, while high in calories, are woefully low in these micronutrients, even when fortified, creating what we refer to as high calorie malnutrition. Against this dietary backdrop, reduced ATP then leads to a constant, low level molecular hypoxia. This is not a hypoxia of obstruction or exertion, but more fundamental. For without proper nutrients, mitochondria can neither utilize oxygen effectively to create ATP, nor do they have sufficient ATP to traffic the O2 into the hemoglobin where it can be pumped into circulation to feed tissues and organs. It is a subtle desaturation, at least initially, but one that initiates all sorts of compensatory reactions to mitigate risk; reactions that are necessary and lifesaving in the short term but become increasingly harmful as time passes.

With insufficient ATP, inflammatory and immune reactions become disrupted and even seemingly chaotic; hormone and electrolyte regulation becomes imbalanced and organ and brain function diminishes. We get disrupted autonomic function (dysautonomia), which cycles back and further disrupts everything else. Depression, anxiety and other mental health issues are also common. This underlying mitochondrial distress is part of the reason why patients with comorbid conditions are at increased risk of not only developing but succumbing to COVID, or really, any virulent pathogen. Their mitochondria are already taxed. They are already carrying low-level hypoxia and, in a very real way, they simply do not have the energy to mount or manage a successful defense.

Now, to add insult to already injured mitochondria, we prescribe medications to manage these conditions rather than correct the root cause, which remember is mitochondrial distress. These medications, while they effectively provide the semblance of health, likely cause more damage to an already damaged system. That is, we get more normal labs, or in the case of antidepressants or anxiolytics, we may feel better, but they do nothing to correct the problem. They only exacerbate it further.

An Unappreciated Factor in COVID Severity and Chronicity

A little appreciated fact in medicine, all pharmaceuticals damage mitochondrial function by some mechanism or another. I have published extensively on this topic here on HM and in our book. Sometimes they deplete critical micronutrients and other times they directly distress, damage and/or deform the mitochondrial membrane by forcibly overriding the regulation of key enzymes involved in ATP production. This, of course, is often compounded by poor nutrition and nearly continuous exposures to chemical toxicants in the environment. It is a perfect cycle of destruction. Poor nutrition causes poorly functioning mitochondria, which decreases ATP while increasing cell level hypoxia, which then initiates inflammation and alters immune reactivity, and rather than correct this, we prescribe medications to override what are necessary reactions to poor nutrition and environmental exposures. These medications then elicit additional damage, further decreasing mitochondrial efficiency and ATP, which necessitates extra nutrients to maintain ATP and stave off more damage.

When we consider the association between COVID severity and comorbid health issues, it must be against the backdrop of nutrition and pharmaceutically and environmentally induced mitochondrial damage. The only variables we can control directly are nutrition and pharmaceutical exposures. We can add more nutrition and we can apply medications more cautiously, but more often than not, we choose to do neither. We ignore nutrient status and stack medications on top of each other endlessly, all the while wondering why the patient’s health continues to decline.

Common Drugs Block Vitamins B1, B9, B12, and CoQ10

To illustrate the state of drug-induced mitochondrial hypoxia that plague so many of the patients threatened by COVID, let us look one common medication that as of 2017, 78 million Americans were taking: metformin. Metformin damages the mitochondria by multiple mechanisms that ultimately lead to reduced ATP, entrenched molecular hypoxia, inflammatory cascades and altered immune reactivity. This, of course, is in addition to the neurological sequelae.

Perhaps the most critical nutrient for in mitochondrial health is thiamine. Thiamine, is blocked by metformin. Metformin blocks vitamin B1 – thiamine – uptake  by multiple mechanisms. When metformin is present, a set of transporters that normally bring thiamine into the cell to perform its task as a cofactor in the machinery that converts carbs to ATP, brings metformin into the cell instead, replacing thiamine altogether. The transporters involved are the SLC22A1, also called the organic cation transporter 1, [OAT1] and the SLC19A3. Metformin also blocks the lactate pathway and acetyl coenzyme A carboxylase (an enzyme necessary to process fatty acids into fuels). Thiamine is critical for mitochondrial function and its position as gateway substrate into the each the of the pathways leading to the electron transport chain, means that insufficient or deficient thiamine limits ATP production, induces cell level hypoxia and all of the inflammatory cascades that go with this process.

Metformin also depletes vitamins B12 and B9, which are responsible for hundreds of enzymatic reactions and particularly important in central nervous system function including myelination (how many cases of diabetic neuropathy or multiple sclerosis are really vitamin b12 deficiency?) One study found almost 30% of Metformin users were vitamin B12 deficient. For the US alone, that’s 26 million people who could be vitamin B12 deficient and likely do not know that they are deficient. What happens when one is B12 deficient? Inflammation increases, along with homocysteine concentrations, which is a very strong and independent risk factor for heart disease (the very same disease metformin is promoted to prevent).  What else happens when B12 is deficient? Poor iron management, better known as pernicious anemia.

Metformin tanks CoEnzyme Q10 which effectively cripples mitochondrial ATP production even further, by as much as 48% in muscles. Imagine having to function in such a reduced capacity. Now imagine having to fight a deadly virus or recover from one. Finally, if the reductions in nutrients and ATP weren’t sufficiently troubling, metformin also interferes with the body’s innate toxicant metabolism pathways, the P450 enzymes, rendering those who use this drug less capable of effectively metabolizing a whole host of other medications and environmental toxicants.

This is one medication. Very few adults who go down this pathway are prescribed just one medication. With metformin, one is likely also to have a statin, perhaps a blood pressure medicine, and if the patient is a women, some form of birth control or hormone replacement. Many are also on antidepressants or anxiolytics. Statins, for example, severely deplete CoQ10, further crippling the electron transport chain. Synthetic hormones deplete a whole host of nutrients (thiamine, riboflavin, pyridoxine, folate, vitamin B12, ascorbic  acid, and zinc) while damaging mitochondria via multiple mechanisms.

Long COVID and Medication

Just as the use of medications leading up to and during the illness impact the functioning of one’s mitochondria, the use of medications across time, as one recovers from the infection, will negatively impact mitochondrial capacity as well. This, of course, is in addition to the demand COVID itself places on mitochondrial energy capacity. Data suggests that at least 10% and upwards of 80% of COVID survivors have lingering symptoms. Among the most common are fatigue, brain fog, muscle pain and weakness, and breathing difficulties along with an array of dysautonomias.  These are classical indicators of ailing mitochondria and yet common treatment protocols involve more of the same medications and none of the nutrients needed to support them. As we go forward and recover from the COVID pandemic, I think it is incumbent upon us to look at mitochondrial health more closely.

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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*Environmental issues should be considered as the totality of chemical exposures from environmental, agricultural, industrial, and pharmaceutical sources. Environmental exposures damage mitochondria and should not be excluded as contributing factors to illness.

Pregnancy Metformin and Fetal Development

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Over the last few decades, metformin or glucophage has become the magic pill de jour for PCOS and type 2 diabetes, so much so that prescriptions for metformin across pregnancy are commonplace. Is it safe? To read the majority of research from early 2000 thru 2010 or so, the answer would be an unequivocal yes. Metformin during pregnancy was considered perfectly safe. Indeed, it was more than safe, it was protective against everything from pre-eclampsia to pre-term birth and it reduced the risk for gestational diabetes significantly.

Like all things too good to be true, once the appropriately sized and controlled studies were conducted researchers found that metformin was not safe. In fact, metformin increased the risk for each of the pregnancy complications it was first presumed to protect against; gestational diabetes, preclampsia and preterm labor, and added a few unexpected and more dangerous ones to boot, like an increased risk for maternal pulmonary embolism and fetal neural tube defects. And yet, it is still recommended regularly.

What has never been addressed is fetal health and long term outcomes. How can a drug that alters insulin sensitivity, a critical function in human health, and that crosses the placenta readily, with umbilical cord concentrations at amounts ranging from at least half that of mom’s to far exceeding maternal concentrations, be safe for fetal development? From a purely logical, perhaps even intuitive, gut reaction this makes absolutely no sense.

What are the consequences of maternal metformin on the developing fetus on insulin regulation and pancreatic function, on growth regulation, cardiac function, neurocognitive function and because of the close relationship between insulin and testosterone, on hormone and reproductive function? Certainly, there must be lasting biochemical changes induced during fetal development; what do we really know about the metformin children? Not much, I am afraid.

That’s about it. That’s all we know. Doctors have been giving metformin to pregnant mamas for decades without so much as a sufficiently controlled and conducted study to support its safety or efficacy. Doctors have been prescribing this drug to pregnant mamas despite the limited research. And although animal studies suggest risks to maternal health and in vitro, cell culture studies indicate potential risk to fetal biochemistry, there seems to be no impetus to cease writing prescriptions or do the research necessary to delineate risks versus benefits.

Wow.

I don’t know about you, but this doesn’t give me a whole lot of confidence in medical science or medical ethics, particularly when one considers the all-too-recent history of thalidomide and DES.

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter. 

This post was published here originally on September 26, 2013.  

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Do Statins Induce Atherosclerosis and Heart Failure?

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Statins are some of the most popularly prescribed medications on the market with 1 in 4 Americans taking statin drugs (2011). Do they work? To read the read the early reports statins were wonder drugs, capable of reducing heart attack and extending lifespan with few side effects. No need to change one’s diet or lifestyle, simply take a statin and live longer.

Over the years, the statin market has expanded to include kids as young as 8 years old: “statin therapy is considered first-line treatment for pediatric patients with abnormal lipid levels.” When combined with our love affair with vaccines, the latest proposal includes a cholesterol vaccine for children at risk for heart disease. And since 75% of Americans are still not heeding the anti-cholesterol warning, intense industry lobbying successfully changed the risk equation for statin prescriptions, immediately expanding the market potential by millions more Americans and billions of additional revenue.

Statins for Health – Maybe Not

With 1 and 4 Americans taking statins and cholesterol levels presumably controlled to within the designated healthy ranges, one might expect a concomitant reduction in heart disease and heart disease related mortality across the population. One would be wrong. Despite controlling cholesterol, Americans are as unhealthy as ever, living with increasingly more chronic diseases and dying at higher rates than ever before. Is it possible we were wrong about the relationship between cholesterol and heart function? Is it possible in our exuberance to offer simple solutions to complex disease processes we have been exacerbating the very conditions we seek to treat? Indeed, it is.

Over the last several years, a growing body of evidence suggests that statins are not only not the wonder drugs we had hoped for, but instead, may be quite dangerous, especially for women. Statins induce diabetes (a major contributor to the metabolic dysfunction implicated in coronary artery disease), increase atherogenesis (the buildup fatty plaques responsible for coronary artery disease), and damage mitochondria, an effect that is exacerbated by exercise. As a result, and in non-industry sponsored studies, statin use is associated with higher rates of all-cause mortality, cancer, heart attack, stroke, than non-statin use. Yikes.

Cholesterol Blues

Just how statins induce such negative effects is linked, in large part, to their primary purpose, cholesterol reduction. We need cholesterol. Cholesterol – fat, forms the structure of all cell membranes. We need healthy cell membranes. Fatty acids provide fuel for the production of mitochondrial energy – ATP. ATP is required for all cell functions. Cholesterol is the primary ingredient for steroid hormone synthesis. Steroid hormones regulate everything from reproduction to heart function to central nervous system activity. We need healthy steroid hormone systems. And if those aren’t reasons enough to reconsider cholesterol, the brain needs cholesterol. Reduce the cholesterol in the brain and brain activity deranges, as evidenced by the increasing recognition of statin induced psychiatric and cognitive sequelae. When we reduce cholesterol artificially, we diminish the functioning of every cell in the body by multiple mechanisms.

Cholesterol and Heart Attack

What about the link between high cholesterol and heart attacks? Isn’t it the cholesterol that causes the plaques that block our arteries and cause all sorts of problems? And, aren’t our high fat, high cholesterol diets to blame for this build up? Perhaps not, and especially for women. According to our good friend Kelly Brogan, atherosclerotic plaques and heart disease represent a ‘multi-factorial inflammatory problem with disparate drivers in different people.’ The latest research suggests that these plaques are ‘not merely the passive accumulation of lipids within artery walls‘ but rather represent oxidative stress (mitochondrial damage) with incessant immune mediated inflammatory signals driven by dietary and other factors. This makes sense when we consider that 90% of first time cardiac events can be prevented with dietary and other lifestyle changes and diet and lifestyle effect mitochondrial functioning significantly (the mitochondria drive inflammation).

The most recent research on diet and nutrition suggests diets high in empty calories, carbohydrates and sugars and low in fat are to blame for heart disease, not the high fat diets we have all been taught to avoid. It should be noted, however, that the relationship between fat and health is complex. Too much or too little impairs mitochondrial functioning.

But Wait, There’s More

A research group out of Japan has gone so far as to claim that statins are not only dangerous for the reasons stated above, but statins induce the very diseases they are promoted to protect against. In their most recent publication, Statins Stimulate Atherosclerosis and Heart Failure: Pharmacological Mechanisms, the researchers boldly argue that:

“statins may be causative in coronary artery calcification and can function as mitochondrial toxins that impair muscle function in the heart and blood vessels through the depletion of coenzyme Q10 and ‘heme A’, and thereby ATP generation.”

In English – statins block a whole bunch of important chemical reactions that induce coronary artery disease where there was none before. They argue, rather persuasively, that statins cause the very disease process that they are promoted to prevent. Whoa.

According to this research group, statins create the environment where fatty plagues grow and thrive. They derail our innate mechanisms to clear those plaques by damaging the mitochondria and, in so doing, damage the very foundation of cell function: mitochondrial energy (ATP) production. Without functioning mitochondria (which we have written about on many occasions), cell damage and cell death occur. With enough damage, tissue and organ damage ensue, and complex multifaceted disease processes develop. Mitochondria are the engines of health. ATP is the fuel. No fuel, no function. Statins damage the engine and block the fuel line.

What’s Worse?

Statins are frequently co-prescribed with Metformin (gluocophage) to reduce glucose in Type 2 diabetes. Metformin damages mitochondria and reduces ATP production even further (more on this in a subsequent post). Combined, these two drugs set the stage for chronic disease and increase the need for additional medications that will also damage mitochondria; a rabbit hole that is not easily climbed out of unless one is willing to look beyond the medical model. Remember, one of the largest global studies on heart health found that 90% of first time cardiac events in men can be prevented with dietary and other lifestyle changes, 94% in women. Diet and lifestyle. Sit with that for a moment. Diet and lifestyle changes are all that are needed for most people to prevent heart attack. Diet and lifestyle.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter.

This article was published originally on June 10, 2015.

Hormones Matter Top 100 Articles of 2015

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Happy New Year, everyone. We have another remarkable year under our belts. Hormones Matter continues to grow month after month. This year, despite the site being down for a month in September, we had over 815,000 visitors, most staying quite a while to read our articles.

Since inception, we’ve published close to 900 articles, many are read by thousands of readers every month. The hysterectomy and endometriosis articles continue to draw large crowds, demonstrating the great need for information in these areas of women’s health.

Our success is thanks to a fantastic crew of volunteer writers who spend countless hours researching complex medical topics, making connections, identifying unconventional therapeutic opportunities, and bringing to light, what are often, invisible illnesses. Without these incredibly talented and compassionate individuals, Hormones Matter would not exist.

Before we begin the new year in earnest, let us take a moment to thank all of the writers of Hormones Matter.

Thank You Hormones Matter Writers!

 

Below are the articles and authors who made the top 100 list for 2015. If you haven’t read these articles, it’s time to do so. If you like them, share them and share our site so we can continue to grow. If you were helped by any of our articles, take a moment and send the writer a thank you note.

This year, we thought we’d do something a little different and include the 25 all-time favorite articles on Hormones Matter. Be sure to scroll down to the second table and take a look. The numbers are quite impressive.

Since we are run by volunteers and unfunded, feel free contribute a few dollars to cover the costs of maintaining operations. Crowdfund Hormones Matter. Every dollar helps.

If you’d like to share your health story or join our team of writers: Write for Us.

Hormones Matter Top 100 Articles of 2015

Article Title and Author

Reads

1. Post Hysterectomy Skeletal and Anatomical Changes -WS 50,814
2. Sex in a Bottle: the Latest Drugs for Female Sexual Desire – Chandler Marrs 47,910
3. Sexual Function after Hysterectomy – WS 28,898
4. In the ER Again – Heavy Menstrual Bleeding -Lisbeth Prifogle 25,326
5. Endometrial Ablation – Hysterectomy Alternative or Trap? -WS 25,048
7.  Adhesions: Cause, Consequence and Collateral Damage – David Wiseman 22, 868
8. Is Sciatic Endometriosis Possible? – Center for Endometriosis Care 11,701
9. Endometriosis: A Husband’s Perspective – Jeremy Bridge Cook 11,626
10. A Connection between Hypothyroidism and PCOS – Sergei Avdiushko 11,024
11. Often Injured, Rarely Treated: Tailbone Misalignment – Leslie Wakefield 10,580
12. Hysterectomy: Impact on Pelvic Floor and Organ Function – WS 8,494
13. Pill Bleeds are not Periods – Lara Briden 8,440
14. Silent Death – Serotonin Syndrome – Angela Stanton 8,408
15.  An Often Overlooked Cause of Fatigue: Low Ferritin – Philippa Bridge-Cook 8,374
16. Wide Awake: A Hysterectomy Story – Robin Karr 7,733
17. How Hair Loss Changed My Life – Suki Eleuterio
18. The High Cost of Endometriosis – Philippa Bridge-Cook 7,170
19. Skin Disorders post Gardasil – Chandler Marrs 6,891
20. Essure Sterilization: The Good, the Bad and the Ugly – Margaret Aranda 6,820
21. Love Hurts – Sex with Endometriosis – Rachel Cohen 6,779
22. Dehydration and Salt Deficiency Migraines – Angela Stanton 6,638
23.  Adverse Reactions, Hashimoto’s Thyroiditis, Gait, Balance and Tremors – Chandler Marrs 6,445
24.  Stop the Metformin Madness – Chandler Marrs 6,400
25. Lupron, Estradiol and the Mitochondria: A Pathway to Adverse Reactions – Chandler Marrs 6,110
26. Endometriosis after Hysterectomy – Rosemary Finnegan 6,093
27. The Reality of Endometriosis in the ER – Rachel Cohen 5,962
28. Mittelschmerz – what should you know – Sergei Avdiushko 5,780
29.  Red Raspberry Leaf Tea to Relieve Menstrual Pain – Lisbeth Prifogle 5,586
30. Mommy Brain: Pregnancy and Postpartum Memory Deficits – Chandler Marrs 5,437
31. Parasites: A Possible Cause of Endometriosis, PCOS, and Other Chronic, Degenerative Illnesses – Dorothy Harpley-Garcia 5,414
32.  Endometriosis and Risk of Suicide – Philippa Bridge-Cook 5,413
33.  Fluoroquinolone Antibiotics and Thyroid Problems: Is there a Connection? – JMR 5, 228
34. Adenomyosis – Philippa Bridge-Cook 5,022
35.  Gardasil: The Controversy Continues – Lisbeth Prifogle 4,809
36.  Hyperemesis Gravidarum – Severe Morning Sickness: Are Mitochondria Involved? – Chandler Marrs 4,801
37.  Oral Contraceptives, Epigenetics, and Autism – Kim Elizabeth Strifert 4,452
38.  High Blood Pressure in Women: Could Progesterone be to Blame? – Chandler Marrs 4,446
39. My Battle with Endometriosis: Hysterectomy at 23 – Samantha Bowick 4,288
40. Thiamine Deficiency Testing: Understanding the Labs – Derrick Lonsdale 4,045
41. My Battle with Endometriosis and Migraines – Angela Kawakami 3,839
42. Tampons with Glyphosate: Underpinnings of Modern Period Problems? – Chandler Marrs 3,835
43. Cipro, Levaquin and Avelox are Chemo Drugs – Lisa Bloomquist 3,792
44. Hysterectomy or Not – Angela’s Endometriosis Update – Angela Kawakami 3,750
45. Warning to Floxies: Beware of New Med for Psoriatic Arthritis – Debra Anderson 3,691
46.  DES – The Drug to Prevent Miscarriage Ruins Lives of Millions – DES Daughter 3,655
47.   Sphincter of Oddi Dysfunction (SOD) – Brooke Keefer 3,540
48. Progesterone for Peripheral Neuropathy – Chandler Marrs 3,278
49. The Fluoroquinolone Time Bomb – Answers in the Mitochondria – Lisa Bloomquist 3,251
50. Why is PCOS so Common? – Lara Briden 3,211
51.  Pregnancy Toes – What Sugar does to Feet – Angela Stanton 2,971
52.  Five Half-truths of Hormonal Contraceptives – The Pill, Patch and Ring – Joe Malone 2,834
53.  Five Years After Gardasil – Ashley Adair 2,831
54. Bleeding Disorders Overlooked in Women with Heavy Periods – Philippa Bridge Cook 2,826
55.  Is Gardasil Mandated in Your State? – Lisbeth Prifogle 2,814
56.  Is Prenatal Dexamethasone Safe: The Baby Makers’ Hubris – Chandler Marrs 2,808
57. Porn Brain – A Leading Cause of Erectile Dysfunction – Chandler Marrs 2,792
58. Lupron and Endometriosis – Jordan Davidson 2,752
59.  Endometriosis, Adhesions and Physical Therapy – Philippa Bridge-Cook 2,746
60.  Glabrata – A Deadly Post Fluoroquinolone Risk You’ve Never Heard About – Debra Anderson 2,703
61. Are You Vitamin B12 Deficient? – Chandler Marrs 2,635
62. Topamax: The Drug with 9 Lives – Angela Stanton 2,635
63.  Cyclic Vomiting Syndrome – Philippa Bridge-Cook 2,622
64.  The Endo Diet: Part 1 – Kelsey Chin 2,614
65.  Endometriosis and Adhesions –  Angela Kawakami 2,544
66.  Thyroid Disease Plus Migraines – Nancy Bonk 2,530
67.  Is it Endometriosis? – Rosalie Miletich 2,414
68. Hysterectomy, Hormones, and Suicide – Robin Karr 2,412
69.  Why I am Backing the Sweetening the Pill Documentary – Laura Wershler 2,321
70.  I Wanted to Die Last Night: Endometriosis and Suicide – Rachel Cohen 2,271
71.  How Can Something As Simple As Thiamine Cause So Many Problems? – Derrick Lonsdale 2,456
72.  Thyroid Dysfunction with Medication or Vaccine Induced Demyelinating Diseases – Chandler Marrs 2,034
73. Angela’s Endometriosis Post Operative Update –  Angela Kawakami 2,017
74.  Fluoroquinolone Antibiotics Damage Mitochondria – FDA Does Little – Lisa Bloomquist 1,993
75.  Endometriosis and Pregnancy at a Glance – Center for Endometriosis Care 1,969
76.  Don’t Take Cipro, Levaquin or Avelox If…. – Lisa Bloomquist 1,960
77.  Gardasil Injured – Dollie Duckworth 1,898
78. Fear of Childbirth Prolongs Labor – Elena Perez 1,888
79. Fluoroquinolone Poisoning: A Tale from the Twilight Zone – Kristen Weber 1,883
80. Personal Story: Thyroid Cancer – Myrna Wooders 1,880
81. Recurrent Miscarriage – Philippa Bridge-Cook 1,873
82. Recovering from the Gardasil Vaccine: A Long and Complicated Process – Charlotte Nielsen 1,842
83. Pelvic Therapy for Endometriosis, Adhesions and Sexual Pain – Belinda Wurn 1,818
84. Hormones, Hysterectomy and the Hippocampus – Chandler Marrs 1,777
85. Why Fatigue Matters in Thyroid Disease – Chandler Marrs 1,718
86. How Do You Deal with the Lasting Effects of Endometriosis? – Samantha Bowick 1,697
87. Depression with Endometriosis – Samantha Bowick 1,678
88. Easing Endometriosis Pain and Inflammation with Nutrition –  Erin Luyendyk 1,648
89. Anti-NMDAR Encephalitis and Ovarian Teratomas – Chandler Marrs 1,634
90. Autoinflammatory Syndromes Induced by Adjuvants: A Case for PFAPA – Sarah Flynn 1,595
91. Endometriosis Awareness Month: A Wish Noted – Philippa Bridge-Cook 1,513
92. The Role of Androgens in Postmenopausal Women – Sergei Avdiushko 1,477
93. It Wasn’t by Choice: Dysautonomia – Margaret Aranda 1,454
94. Fluoroquinolone Antibiotics Associated with Nervous System Damage – Lisa Bloomquist 1,453
95.  Vitamin D3 and Thyroid Health – Susan Rex Ryan 1,439
96. Dealing with Doctors When You Have Undiagnosed Endometriosis -Angela Kawakami 1,439
97. Endometriosis and Being a Trans Person: Beyond Gendered Reproductive Health – Luke Fox 1,436
98. Cyclic Vomiting Syndrome and Mitochondrial Dysfunction: Research and Treatments – Philippa Bridge-Cook 1,430
99. Living with Ehlers Danlos is Hell – Debra Anderson 1,420
100. What is Fluoroquinolone Toxicity? – Lisa Bloomquist 1,415

Hormones Matter All-Time Top 25 Articles

Article Title and Author

Reads

1. Post Hysterectomy Skeletal and Anatomical Changes -WS 105,336
2. Sex in a Bottle: the Latest Drugs for Female Sexual Desire – Chandler Marrs 99,098
3. Endometrial Ablation – Hysterectomy Alternative or Trap? -WS 70,999
4. Adhesions: Cause, Consequence and Collateral Damage – David Wiseman 40,299
5. In the ER Again – Heavy Menstrual Bleeding -Lisbeth Prifogle 39,821
7.  Sexual Function after Hysterectomy – WS 35,188
8. A Connection between Hypothyroidism and PCOS – Sergei Avdiushko 31,193
9. Is Sciatic Endometriosis Possible? – Center for Endometriosis Care 24,691
10. Endometriosis: A Husband’s Perspective – Jeremy Bridge-Cook 23,251
11. Skin Disorders post Gardasil – Chandler Marrs 18,105
12.  Gardasil: The Controversy Continues – Lisbeth Prifogle 14,174
13.  Wide Awake: A Hysterectomy Story – Robin Karr 14,134
14.  Endometriosis and Risk of Suicide – Philippa Bridge-Cook 13,836
15.  Love Hurts – Sex with Endometriosis – Rachel Cohen 13,782
16. Endometriosis after Hysterectomy – Rosemary Finnegan 13,294
17. Hysterectomy: Impact on Pelvic Floor and Organ Function – WS 13,056
18.  Adverse Reactions, Hashimoto’s Thyroiditis, Gait, Balance and Tremors – Chandler Marrs 12,901
19.  How Hair Loss Changed My Life – Suki Eleuterio 12,835
20. Mittelschmerz – what should you know – Sergei Avdiushko 11,919
21.  Often Injured, Rarely Treated: Tailbone Misalignment – Leslie Wakefield 11,521
22.  An Often Overlooked Cause of Fatigue: Low Ferritin – Philippa Bridge-Cook 10,821
23.  Mommy Brain: Pregnancy and Postpartum Memory Deficits – Chandler Marrs 10,591
24. Adenomyosis – Philippa Bridge-Cook 10,249
25.  I Wanted to Die Last Night: Endometriosis and Suicide – Rachel Cohen 9,826

Stop the Metformin Madness

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I have never been a fan of Metformin. It seemed too good to be true. Many years ago I had a conversation with a researcher about all of its possible therapeutic indications. His lab was actively pursuing the anti-cancer angle. That should have been a clue that Metformin might be causing more damage than we recognized, but it wasn’t. At that point, I was still enamored with the wonders of pharmacology and hadn’t yet begun my path toward understanding medication adverse reactions. Indeed, it wasn’t until very recently, when a family member began suffering from one of these reactions, that I began my investigation in full. This is what I learned.

Type 2 Diabetes is Big Business

The global profits from Type 2 diabetes medications rested at a paltry 23 billion dollars in 2011 but are expected to grow to over $45 billion annually by 2020. The market growth is bolstered in large part by the ever-expanding demand for therapeutics like Metformin or Glucophage. Metformin is the first line of treatment and standard of care for insulin resistance across all populations of Type 2 diabetics with over 49 million Americans on Metformin in 2011-2012. It is particularly popular in women’s health with an increasing reliance on Metformin for the metabolic dysfunction observed in women with PCOS, PCOS-related infertility, and even gestational diabetes. Metformin is prescribed so frequently and considered so innocuous that it is sometimes euphemistically referred to as vitamin M.

If we quickly scan the safety research for metformin, there is little immediate evidence suggesting any side effects whatsoever. In fact, in addition to controlling blood sugar by blocking the hepatic glucose dump, this drug is suggested to promote weight loss, increase ovulation in women, (thereby helping achieve pregnancy), and prevent an array of pregnancy complications (everything from miscarriage to gestational diabetes, pre-eclampsia and preterm birth). Metformin is argued to prevent cancer and the neurocognitive declines associated with aging, even aging itself. By all accounts, Metformin is a wonder drug. Why isn’t everyone on Metformin prophylactically? Increasingly, we are.

With the increasing rates of obesity and associated metabolic disturbances, drugs that purportedly reduce those indicators are primed for growth. Like the push to expand statin prescription rates from 1 in 4 Americans to perhaps 1 in 3, millions have been spent increasing the therapeutic indications and reach for this medication. Amid all the excitement over this drug, one has to wonder if it isn’t too good to be true. In our exuberance to get something for nothing, to have cake, if you will, have we overlooked the very real risks and side effects associated with Metformin?  I think we have.

Metformin and Vitamin B12 Deficiency

As we’ve reported previously, Metformin leaches vitamin B12 and to a lesser degree B9 (folate) from the body. One study found almost 30% of Metformin users are vitamin B12 deficient. For the US alone, that’s almost 15 million people who could be vitamin B12 deficient and likely do not know that they are deficient. What happens when one is vitamin B12 deficient?

Firstly, inflammation increases, along with homocysteine concentrations, which is a very strong and independent risk factor for heart disease (the very same disease Metformin is promoted to prevent).  And that is the tip of the iceberg.

Vitamin B12 is involved with a staggering number of physiological functions including DNA, RNA, hormone, lipid, and protein synthesis. Deplete vitamin B12 and a whole host of problems emerge, mostly neurological.

Vitamin B12 is critical for the synthesis of the myelin sheaths around nerve fibers. There is a growing relationship between multiple sclerosis, which involves the disintegration of myelin and brain white matter, and vitamin B12 deficiency.  Often the first signs of B12 deficiency are nervous system-related with cognitive disturbances and peripheral neuropathy among the most common.

Additionally, many women have dysregulated hormones connected to vitamin B12 deficiency. In light of the Metformin-mediated vitamin B12 deficiency, one has to wonder if some of the chronic health issues plaguing modern culture are not simply iatrogenic or medication-induced.

Metformin, Pregnancy and Maternal and Fetal Complications

Considering that half the population is female, many of whom are on Metformin and may become pregnant, we must consider the potential effects of Metformin-induced vitamin B12 deficiency during pregnancy. As troubling as the effects of B12 deficiency are on non-pregnant individuals, during pregnancy they can be devastating. Vitamin B12 deficiency during pregnancy leads to an increased incidence of neural tube defects and anencephaly (the neural tube fails to close during gestation). Once thought to be solely related to folate deficiency (vitamin B9) which Metformin also induces, researchers are now finding that B12 has a role in neural tube defects as well.

Scan the internet for Metformin and infertility and you’ll see long lists of fertility centers boasting the benefits of this drug. During pregnancy, the exuberance for vitamin M is palpable, although entirely misplaced. Early reports suggested Metformin would reduce an array of pregnancy complications including gestational diabetes. The data supporting these practices were mixed at best. At worst, however, they were downright incorrect. Metformin, it appears, may evoke the very conditions it was promoted to prevent during pregnancy and then some. Additionally, recent research suggests Metformin alters fetal development and induces long-term metabolic changes in the offspring, likely predisposing the children to Type 2 Diabetes, an epigenetic effect perhaps.

Metformin Inhibits Exercise-Induced Insulin Sensitivity

As if those side effects were not enough to question mass Metformin prescribing practices, it appears that Metformin reduces any gains in insulin sensitivity that normally would be achieved from exercise. I cannot help but wonder if Metformin impairs insulin signaling in general. Cancercancer research suggests that it might.

According to one study, physical exercise can increase insulin sensitivity by up to 54% in insulin-resistant individuals, unless of course, they are taking Metformin. Metformin abolishes any increased insulin sensitivity gained by exercise. Metformin also reduces peak aerobic capacity, reducing performance and making exercise more difficult. Moreover, despite claims to the contrary, Metformin does not appear to be an especially effective tool for weight loss, netting a reduction of only 5-10 pounds over 4-8 months. Regular exercise and a healthy diet net on average a loss of 5-10 pounds per month for most people and are significantly more effective at reducing diabetes and associated health complications without the potential side effects.

Metformin and Mitochondrial Damage

Perhaps most troubling amongst the Metformin side effects is its ability to severely impair mitochondrial functioning.

Recall from high school biology, the mitochondria are those bean-shaped organelles inside cells that are responsible for cellular respiration or energy production. Through a variety of pathways, the mitochondria provide fuel for cell survival. In addition to cellular energy production, mitochondria control cell apoptosis (death), calcium, copper, and iron homeostasis, and steroidogenesis. In essence, mitochondria perform the key tasks associated with cell survival, and indeed, human survival. Damage the mitochondria and cellular dysfunction or death will occur. Damage sufficient numbers of mitochondrion and chronic, multi-symptom illness arises.

As we have come to learn, many pharmaceuticals, environmental toxicants, and even dietary deficiencies can impair mitochondrial functioning and induce disease processes that are often difficult to diagnose and treat. Metformin is no different. Metformin impairs mitochondrial functioning quite significantly by several mechanisms and, in doing so, sets off a cascading sequence of ill effects.

At the center of metformin’s mitochondrial damage is its effect on the most basic of mitochondrial functions – ATP (cellular energy) production. Metformin reduces mitochondrial ATP production in skeletal muscle by as much as 48%. Sit with that one for a moment, a 48% reduction in cell fuel. Imagine functioning at only half capacity. This would make basic activities difficult at best and exercising to lose weight a very unlikely proposition. Imagine similar reductions in ATP production were observed in the brain or the heart or the GI tract (which, when on Metformin are likely), the types of disturbances we might see become quite clear: neurocognitive decline, psychiatric instability, neuropathy, heart rate, rhythm and blood pressure abnormalities, along with gastrointestinal distress to name but a few. Underlying all of these symptoms, and indeed, all mitochondrial dysfunction is an overwhelming sense of fatigue and malaise.

Metformin Alters Immune Reactivity via the Mitochondria

As I wrote in a previous post:

Some researchers argue that the mitochondria are the danger sensors for host organisms; having evolved over two billion years to identify and communicate signs of danger to the cells within which they reside. The signaling is simple and yet highly refined, involving a series of switches that control cellular energy, and thus, cellular life or death. When danger is present, energy resources are conserved and the immune system fighters are unleashed. When danger is resolved, normal functioning can resume.

If the danger is not resolved and the immune battles must rage on, the mitochondria begin the complicated process of reallocating resources until the battle is won or the decision is made to institute what can only be described as suicide – cell death. Cell death is a normal occurrence in the cell cycle of life. Cells are born and die for all manner of reasons. But when cell death occurs from mitochondrial injury, it is messy, and evokes even broader immune responses, setting a cascade in motion that is difficult to arrest.

Metformin alters this process, first by damaging the mitochondrial ATP factory and reducing energy production capacity and then by inhibiting the signaling cascades that would normally respond to the danger signals. The double hit fundamentally alters immune function and I would suspect predisposes those who take Metformin to more infections and an array of inflammation-based disease processes. More details on this in a subsequent post.

Metformin and the Statins: Beware

The mechanisms through which Metformin derails mitochondrial functioning are complex but likely related to depletion of coQ10, an enzyme involved in what is called the electron transport chain within the mitochondria. CoQ10 also referred to as ubiquinol and ubiquinone, is critical for mitochondrial functioning. Recall from a previous post, that statins, like Lipitor, Crestor and others also deplete coQ10 and from a pharmacological perspective these mechanisms are implicated in the development of atherosclerosis and heart failure.

“statins may be causative in coronary artery calcification and can function as mitochondrial toxins that impair muscle function in the heart and blood vessels through the depletion of coenzyme Q10 and ‘heme A’, and thereby ATP generation.”

CoQ10 depletion is also implicated in the more common statin-induced side effects like muscle pain and weakness and in severe cases, rhabdomyolysis. Since Metformin and statins are regularly co-prescribed, the potential for severely depleted mitochondria and significant side effects is very high. Consider muscle pain and weakness among the first signs of problems.

My Two Cents

When we contrast the reduction in glucose mediated by Metformin with the damage this medication does to the mitochondria and immune signaling, along with its ability to leach vitamin B12, block insulin sensitivity and reduce aerobic capacity, one cannot help but wonder if we are causing more harm than good. Admittedly, obesity and hyperglycemia are growing problems in Western cultures. As we are coming to learn, however, obesity itself is not linked to the diseases processes for which many drugs like statins and Metformin are promoted to protect against – the obesity paradox. Growing evidence suggests that obesity is indicative of mitochondrial dysfunction and chemical exposures which then may provoke impaired insulin sensitivity and hyperglycemia and continued fat storage versus metabolism. If this is true, simply reducing circulating glucose concentrations, in an effort to reduce obesity and the purported health problems associated with obesity, will do nothing to treat the underlying problem.

Insulin resistance and the associated hyperglycemia are environmental and lifestyle-mediated problems that should be reversible with environmental and lifestyle changes. Having said that, those lifestyle and dietary changes will fail unless we consider the underlying mitochondrial damage initiated by dietary choices, pharmaceuticals, and other environmental exposures. For that, we must dig deeper into mitochondrial functioning and correct what we can.

I believe obesity and hyperglycemia are symptoms of damaged and dysfunctional mitochondria, partly mediated by lifestyle, partly iatrogenic (pharmaceutically induced), and likely epigenetic. If we are to solve the ‘obesity’ problem and prevent the damage mediated by hyperglycemia, we have to address these variables. Failing to do so serves no one except those who profit from our continued ill-health.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, and like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter. 

PCOS, Pregnancy, Metformin and Vitamin B12 Deficiency

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PCOS or polycystic ovarian syndrome is one of the most common hormone disorders in women. It is marked by a triad of symptoms that include: cardiovascular, metabolic and steroid hormone disturbances. Type II diabetes is common in PCOS and Metformin is the drug of choice to treat PCOS – related Type II diabetes.

In recent years, clinicians and researchers have begun to observe vitamin B12 deficiency in Metformin users. First thought to be a short term problem, researchers are now finding that with long term metformin use not only does the B12 deficiency persist, but it grows. Left alone long enough, vitamin B12 deficiency leads to a host of conditions, many that  Metformin was supposed to prevent, including:

For women, especially of reproductive age, B12 deficiency can be particularly troubling, if not downright dangerous. Vitamin B12 deficiency during pregnancy leads to an increased incidence of neural tube defects and anencephaly (the neural tube fails to close during gestation – anencephaly pictured above) . Once thought to be solely related to folate or folic acid deficiency (vitamin B9), researchers are now finding that B12 has a role in neural tube defects as well. Many women on Metformin are coming into pregnancy vitamin B12 deficient.

This is where it gets tricky. Metformin is used in women with PCOS to reduce insulin sensitivity. Metformin also tends to regulate ovulation for PCOS women and was believed to help women get pregnant (though the data here are mixed here as well). Without regular ovulation, conceiving is near impossible and so the fact that Metformin might have helped with ovulation had been seen as a breakthrough for previously infertile PCOS women. Reproductive endocrinologist embraced this new found fertility tool and as one might expect, the requisite studies (read marketing documents) flooded the esteemed peer-reviewed journals to proclaim the benefits of this new wonder drug. No wait, Metformin is not a drug, it’s a new vitamin – Vitamin M.

We now have a drug that is given liberally to women who become pregnant and then continued across the pregnancy. The drug crosses the placental barrier and there are no studies to indicate either its safety or harm to the fetus. The drug causes significant vitamin B12 deficiency, which alone poses great risk to fetal development (neural tube defects) but who knows what vitamin B12 deficiency plus the endocrine disrupting effects Metformin will have on the developing fetal insulin or cardiovascular systems. Are we looking at more transgenerational effects?  Metformin does not prevent maternal gestational diabetes (as was widely speculated) and increases pre-eclampsia, pulmonary embolism and other nasty pregnancy complications.  And yet, the major patient organizations advocate for its use across pregnancy.

Have we learned nothing from thalidomide and DES?  Apparently, not.

 

Photo credit: Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities