Metformin And Lactic Acidosis: What’s The Link?

Many patients with type 2 diabetes are put on metformin. 

Are you one of them? Did your doctor explain to you the risks of lactic acidosis? If not, you’ll want to read this article. 

Many people are familiar with lactic acid buildup as a result of exercise. Are you familiar with that achy feeling in your muscles during or after a challenging workout? That right there is lactic acidosis.

If your lactic acidosis results from exercise, that will usually resolve on its own. But lactic acidosis can also happen throughout your body. 

Because this can be dangerous, it’s important to recognize the signs and symptoms of lactic acidosis. And if you recognize any of these symptoms in you, get treated right away.

What is metformin?

Metformin is a prescription drug that helps treat type 2 diabetes. It belongs to a medication class called biguanides.

Metformin does not cure diabetes. It does help to lower your blood sugar levels to a safe range.

Doctors also prescribe metformin off-label for polycystic ovary syndrome. However, metformin is not FDA approved for this use.

Most metformin side effects aren’t severe. They tend to target the digestive system. Lactic acidosis is a rare side effect, but it can be severe and require prompt medical attention.

RELATED: Metformin Recall: Is Your Medication Affected?

What is lactic acidosis?

Lactic acidosis is a form of metabolic acidosis. When your body overproduces or underutilizes lactic acid and your body can’t keep up, lactic acidosis occurs. When this happens, your body cannot metabolize the lactic acid quickly enough.

Lactic acidosis can have a quick onset that appears within minutes. It might happen gradually, over a few days.

If you are experiencing lactic acidosis, it may be a problem in your liver. Or it’s possible that (in the case of chronic kidney disease) your kidneys are having a hard time removing excess acid from the body due to renal impairment or renal dysfunction/renal insufficiency.

If lactic acid is building up in the body faster than it can clear it out, the acidity of your blood will rise. This causes your body’s pH level to go down. Your body wants to have a pH that is slightly alkaline and not acidic.

Lactic acid builds up in the muscles when there isn’t enough oxygen to break down glycogen and glucose. This is anaerobic metabolism.

There are two forms of lactic acid. One is L-lactate and D-lactate. If you are experiencing lactic acidosis, it is more likely to be a buildup of L-lactate levels.

There are also two forms of lactic acidosis. Type A lactic acidosis is caused by the following:

  • Low blood volume
  • Cardiac failure
  • Sepsis
  • Cardiopulmonary arrest

Type B lactic acidosis is caused by impaired cellular functioning and low oxygen perfusion of tissues.

Metformin toxicity is quite treatable. If you do get lactic acidosis, you’ll want to treat it right away because it can be life-threatening if left untreated.

People who are on metformin and develop lactic acidosis are called MALA patients (metformin-associated lactic acidosis patients).

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What are the signs of lactic acidosis?

If you experience any symptoms of lactic acidosis, it’s important that you talk to your doctor right away. Your doctor should help you to find out what the root cause is. 

The difficulty with lactic acidosis symptoms is that they overlap with symptoms of other health issues. This is where your doctor can help.

Symptoms of lactic acidosis (metformin poisoning) include the following:

  • Exhaustion
  • Extreme fatigue
  • Muscle cramps
  • Muscle pains
  • Body weakness
  • An overall feeling of discomfort
  • Abdominal discomfort
  • Abdominal pain
  • Diarrhea
  • Headache
  • Low appetite
  • Rapid heart rate

Your doctor can diagnose lactic acidosis through a fasting blood test. You may need to fast and reduce your activity level for eight to ten hours before taking a lactic acidosis test.

This test is usually conducted by taking blood from a vein in your hand. This is because clenching your fist or having a band around your arm can lead to a falsely elevated acid level. So lab techs will take blood from the hand rather than the typical arm.

Can metformin cause lactic acidosis?

Biguanides can lead to a buildup of lactic acid levels. Metformin, also called Glucophage, is a type of biguanide medication. Metformin helps in the treatment of diabetes, renal failure, and polycystic ovarian syndrome.

If you have diabetes, have an increased metformin concentration, and have kidney disease, then you may be at higher risk of lactic acidosis. If you fall into those categories and experience any of the symptoms of lactic acidosis, seek urgent diabetes care immediately.

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Factors that increase your risk of lactic acidosis while taking metformin

Medical conditions

Certain medical conditions can increase your risk of lactic acidosis.

One of these conditions is heart disease. Congestive heart failure and cardiac arrest can slow the flow of blood, and thus oxygen, around the body. This can lead to a spike in lactic acid levels.

Sepsis can also cause a spike in lactic acid due to a lower oxygen flow. If you have a severe viral or bacterial infection, this could then lead to sepsis if left untreated.

Cancer cells can lead to the production of lactic acid. Once patients experience cachexia, they can lose quite a bit of weight. This can compound the lactic acid buildup, making things even worse.

Short bowel syndrome, also called short gut, can also lead to lactic acidosis. The good news is that this condition is rare. 

If you have short bowel syndrome, there could be bacterial overgrowth in your small bowel. This can then lead to a buildup of D-lactic acid. This same thing can happen in patients after gastric bypass surgery.

Other medical conditions that can increase your risk of lactic acidosis include the following:

  • Carbon monoxide poisoning
  • Cholera
  • Asphyxiation
  • Malaria
  • Acute kidney injury leading to acute renal failure

Medications

Medications for Human Immunodeficiency Virus (HIV) can spike lactic acid levels. The biggest culprits for this are nucleoside reverse transcriptase inhibitors. They can damage your liver, too. 

As we mentioned earlier in this article, liver damage makes it harder for your body to process lactic acid.

If you use Tylenol (acetaminophen) often, then this can lead to lactic acidosis and severe acidemia. It is important to note that this can still happen even if you take the dose as directed on the label. 

Acetaminophen can increase the buildup of pyroglutamic acid in the blood, which can then lead to lactic acidosis.

Diet and lifestyle

Chronic alcoholism can lead to lactic acidosis and alcoholic ketoacidosis. Alcoholic ketoacidosis is treatable with intravenous hydration and glucose. However, if you don’t get it looked at it right away, then it can prove to be fatal. 

Alcohol boosts phosphate levels in the body. This can lead to lower kidney function. Since damaged kidneys can’t clear lactic acid as efficiently, this can lead to a more acidic pH in the body. If you have chronic alcoholism and are taking metformin therapy for diabetes, it’s crucial that you seek help.

Intense exercise can lead to lactic acid buildup. This tends to happen when your body doesn’t have enough oxygen to break down glucose in the blood. Symptoms to look out for are a burning sensation in your muscles, nausea, and weakness.

Metformin accumulation can make all of the above even worse.

Complications of lactic acidosis

Some symptoms of severe lactic acidosis are emergent. If you have any of these symptoms and suspect you have lactic acidosis, it’s crucial that you seek care right away. If this is the case, go to your local emergency room or dial the emergency number to seek critical care. 

The symptoms of lactic acidosis that constitute a medical emergency include the following:

  • Jaundice (yellow skin and/or whites of the eyes)
  • Confusion
  • Difficulty breathing or rapid, shallow breaths
  • Fruity smelling breath

If your breath smells like fruit, this is a symptom of ketoacidosis, which is a serious complication of diabetes mellitus.

Treatment for lactic acidosis

As with any medical condition, the best course of action is to address the root cause. Lactic acidosis is no exception here. This is why treatment for lactic acidosis depends on how it occurred in the first place. 

For example, if it started with abnormal renal function, then continuous renal replacement therapy or intermittent hemodialysis may be appropriate and what your doctor recommends.

However, if lactic acidosis is presenting with symptoms representing a medical emergency, then health care professionals will need to treat the symptoms. In emergencies, the root cause is not as crucial as stabilizing your body.

To reduce lactic acid levels, health care professionals may give you intravenous fluids to increase oxygen to the tissues.

If you have lactic acidosis due to exercise, you can likely treat this on your own at home. Stop exercising, rest, and hydrate. Drink water or an electrolyte replacement sports drink.

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How to reduce your risk of lactic acidosis while taking metformin

You can treat lactic acidosis from exercise by staying well hydrated. It’s also important to have long rest periods between your sessions of physical activity.

If you are undergoing metformin treatment, it is crucial that you don’t abuse alcohol to prevent metformin intoxication lactic acidosis from happening. Otherwise, this could become serious and lead to you being admitted to the intensive care unit.

Conclusion

If you have type 2 diabetes, you are likely familiar with the medication metformin. You may even be one of those metformin-treated patients yourself. 

However, you may not be so in the know about lactic acidosis. Until now! Be sure to look out for any of the signs of lactic acidosis. Be aware of and minimize any factors in your life that may increase your risk of lactic acidosis.

If you have any of the symptoms of metformin-associated lactic acidosis complications, it’s crucial you seek urgent care. And if you do this, you will likely be treated with intravenous fluids. 

If you have type 2 diabetes, take metformin, and want to reduce your risk of lactic acidosis, then minimize your alcohol intake and be sure to have long resting periods between exercise sessions.

If you have any questions about your metformin use and how to prevent lactic acidosis, speak to your health care provider today.

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Sources

  1. Andersen, LW; Mackenhauer, J; Roberts, JC; Berg, KM; Cocchi, MN & Donnino, MW. (2013). Etiology and therapeutic approach to elevated lactate levels. Mayo Clinic Proceedings. 88 (10), P1127-40. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975915/ 
  2. Fulop, M. (1989). Alcoholism, ketoacidosis, and lactic acidosis. Diabetes Metab Rev. 5 (4), 365-78.
  3. Gupta, K. (2016). Cancer generated lactic acid: Novel therapeutic approach. International Journal of Applied & Basic Medical Research. 6 (1), 1-2.
  4. Lipska, KJ; Bailey, CJ & Inzucchi, SE. (2011). Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care. 34 (6), 1431-7.
  5. Puwanant, M; Mo-Suwan, L & Patrapinyokul, S. (2005). Recurrent D-lactic acidosis in a child with short bowel syndrome. Asia Pac J Clin Nutr. 14 (2), 195-8. https://pubmed.ncbi.nlm.nih.gov/15927940/ 
  6. Suetrong, B & Walley, KR. (2016). Lactic acidosis in sepsis: It’s not all anaerobic. Contemporary Reviews in Critical Care Medicine. 149 (1), P252-61.

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