Sodium dichloroacetate

Sodium dichloroacetate, commonly referred to as DCA, is a salt of sodium and dichloroacetic acid. The formula of the compound is Cl2 CH COONa. 

Key characteristics and interesting facts about DCA

• The structure of the DCA molecule resembles the combination of table salt and vinegar.
• Under normal conditions, DCA appears in a white, powder form and is soluble in water.
• Sodium dichloroacetate is not patentable.
• There are no restrictions on its transportation; it can be freely sold without strict regulations.

Production and Occurrence of DCA

The compound is normally synthesized in laboratories. However, small quantities are widespread in the environment as a side product of water chlorination. DCA can also naturally occur in a variety of red algae including Asparagopsis taxiformis.

Medical Uses of DCA

Sodium Dichloroacetate has a long history of use in medicine.

• It has been used for the treatment of children with genetic mitochondrial disorders for over 40 years.
• Its pharmacology was extensively studied.
• DCA has been researched in cells, animals, children and adults for various conditions as a monotherapy or in combination with other therapies.

Table of Content

• Story of DCA
• How DCA works?
• Sodium dichloroacetate dosage
• DCA safety and side effect prevention

Story of DCA

• 1983 Congenital lactic acidosis
• 1987 Ischemic stroke / Heart attack
• 2007 Cancer
• 2017 Pulmonary arterial hypertension
• 2018 Chronic fatigue syndrome
• 2019 Endometriosis

Sodium dichloroacetate is a fascinating little molecule. The first contributions to its research began at the 70s. Slowly but surely it grew into an exercise in lateral thinking, bringing people all over the world together. (Ref.)

Hundreds of published studies, some of them funded by the FDA, attempted to reveal whether this medication could become a new way of treating various incurable illnesses. (Ref.)

On the flip side, since DCA is frequently found in the water around us, authorities such as the U.S. and the Australian government financed scientists to investigate the safety of this unknown substance. (Ref.)

Soon after, DCA has received a lot of attention by becoming a drug that can help in managing a wide variety of diseases. This very day it remains the only available medicine for treating children with inherited errors of mitochondrial metabolism. (Ref.)

DCA has also demonstrated efficacy in controlling conditions such as diabetes, elevated serum cholesterol and triglycerides as well as amyotrophic lateral sclerosis (ALS). (Ref.¹), (Ref.²), (Ref.³), (Ref.⁴)

Over the past decades, the molecule has found its place among dozens of clinical trials with patients. The studies involving Sodium dichloroacetate display success in managing common, but difficult to treat conditions including pulmonary arterial hypertension, chronic fatigue syndrome, endometriosis and malignancies. (Ref.¹), (Ref.²), (Ref.³), (Ref.⁴)

Nowadays, DCA is not only frequently seen in ongoing clinical research, the medication is also used to treat people in alternative medicine clinics globally. Besides, Sodium dichloroacetate is often offered to patients as an off-label drug in primary health care.

Congenital Lactic Acidosis

• Since 1983 Dichloroacetate has been put into practice to treat children with congenital lactic acidosis. DCA improves the quality of life as well as the survival of patients that suffer from dangerous mitochondrial disorders. (Ref.1), (Ref.2)

The medication does so by stimulating the Pyruvate dehydrogenase complex enzymes located in our mitochondria. When aerobic glucose oxidation and lactic acid oxidation are enabled again, normal cellular metabolism can once again take place.

Children that use DCA achieve lower serum concentrations of lactate, and thus develop less severe systemic metabolic acidosis. This allows these young patients to live a healthier life, especially in combination with other medical interventions.

Above all, the previous clinical trials, that included DCA for childhood disease treatment, hold a significant role in determining the optimal and safe concentrations for therapeutic purposes.

The side effects and long-term safety of the drug were closely investigated during the long years of research, which allowed for a quick transition to treating other medical conditions. (Ref.)

Ischemic Stroke / Heart Attack

• Since 1987 DCA has been researched on managing the outcome of ischemic strokes and heart attacks. Several important mechanisms were found to be key in supporting recovery from these medical emergencies.

Essentially, dichloroacetate prevents post-hypoxic lactate accumulation in the damaged tissue, thus lowering the chances of a poor outcome. In case of myocardial infarction, DCA significantly improves the function of the injured heart. (Ref.¹), (Ref.²)

Cancer

• In 2007, the antitumor effect of Sodium dichloroacetate has been discovered. Surprisingly, this amazing breakthrough happened by accident.

The research team, led by Dr. Evangelos Michelakis, was examining Sodium dichloroacetate as a novel way to handle heart disorders. During the investigation, scientists noticed that the chemical imbalances occurring within tumor cells and mitochondria could be a potential target to cure neoplasms with DCA.

To test this discovery, the researchers implanted tumor cells of brain, breast and lung in rats. Once the DCA treatment was applied, the majority of cancer cells died, some of the tumors began shrinking within hours. The action of the compound left healthy and normal cells unharmed.

It appeared that the experimental rodents did not suffer any toxic side effects. On top of that, the tumor cells dramatically decreased in size. The outcome was certainly different from conventional chemotherapy.

The discovery became pivotal in understanding that malignant diseases could be successfully treated by restoring and maintaining normal cellular metabolism in cancer cells. In the same year, a paper of these scientific reports soon became public. (List of studies – DCA for cancer)

This innovative approach sparked a huge interest globally. Shortly afterwards more in vitro and in vivo experiments confirmed the powerful evidence of Sodium dichloroacetate‘s antitumor activity.

Inevitably, doctors and patients became very keen to see if the repurposed drug could reach the clinical setting. This eventually led to one of the first human DCA clinical trials in 2010. The results of the trial were promising, however, without adequate funding additional research became impossible. (Ref.)

Sadly, since it is a cheap, widely available drug that had its patent expire a decade ago, no pharmaceutical companies were interested in funding more clinical investigations since it would provide no profit. Therefore, the progress in DCA research remained slow-moving.

Nevertheless, additional small clinical trials and published clinical cases guided to a better understanding on how DCA could be used to handle malignant diseases.

Today it‘s known that the substance can be used as a powerful tool in cancer treatment. (Ref.)

That is why DCA has been used as an alternative therapy for cancer treatment under professional medical supervision in one of Canada‘s first DCA clinics.

In the years ahead, dozens of innovative, integrative medical centers in America, Europe as well as Asia started leading the way in redefining cancer treatment with Sodium dichloroacetate.

For more information, please visit the DCA for Cancer page.

• In 2017, one of the first clinical studies that used DCA for improving the health of people with pulmonary arterial hypertension (PAH) was completed. (Ref.)

PAH is a progressive disease in which the blood vessels become stiffened due to excess muscle tissue in the walls of pulmonary arteries. In that case, the blood has a harder time reaching the lungs from the heart where it gets oxygenated.

A group of scientists from Canada discovered that these altered muscle cells have tumor-like characteristics that can be reversed and treated with Sodium dichloroacetate. They proposed that metabolism plays a vital role in the development of the disease and decided to test this
theory out in real-life conditions. (Ref.)

Soon after, a clinical trial of 20 participants revealed that genetically susceptible pulmonary arterial hypertension patients respond to DCA treatment with a measurable decrease in their lung hypertension. Within 1-3 months people experienced an improvement of symptoms in everyday life coupled with a notable physical recovery.

The positive results were observed in participants that took Sodium dichloroacetate in combination with other PAH treatments such as Sildenafil.

Read the article – how DCA can improve symptoms of pulmonary arterial hypertension?

Chronic Fatigue Syndrome

• In 2018, a pilot trial in Europe, Belgium, demonstrated that DCA could treat the symptoms of Myalgic encephalomyelitis / Chronic fatigue syndrome (ME / CFS).

Over half of the patients that participated in the clinical study reported an average 60% positive improvement in their fatigue scores. Many members of the ME / CFS online community later on managed to achieve comparable results when using a similar DCA protocol. (Ref.¹)

The energy in our body is mostly generated by mitochondria, also known as the powerhouses of the cell. It is hypothesized that ME / CFS patients have impaired function of these cellular little structures, which leads to extreme fatigue.

Notably, Sodium dichloroacetate is known to restore mitochondrial activity. This could explain why DCA can result in replenished energy levels and an overall improvement in ME / CFS patients.

The original DCA for ME / CFS protocol also involves additional food supplements that contribute to the health of mitochondria.

Learn more about Myalgic encephalomyelitis / Chronic fatigue syndrome and how it can be treated with DCA.

Endometriosis

• In 2019, an Endometriosis research group from the University of Edinburgh discovered that the disease could successfully be managed by using DCA.

Endometriosis is a chronic condition that causes debilitating pain, uncomfortable sexual intercourse, heavy periods and infertility. It is estimated that 1 out of 10 women between the ages of 18 and 40 years will suffer from this condition. Unfortunately, there is no cure and in the last decades there have been no major advances in treating the disease. (Ref.)

Interestingly, through trial-and-error scientists discovered that displaced endometrial cells have a different metabolic type compared to those in healthy women. In vitro research showed that Endometriosis cells produce higher concentrations of lactate, which perhaps could be plummeted with Sodium dichloroacetate.

The theory was soon tested in laboratory models. Having the newly acquired knowledge, the investigators managed to achieve marked size reduction in mice endometriotic lesions in just a week. (Ref.)

The study convinced the researchers that DCA could finally be the missing key in handling Endometriosis symptoms. In a short time, an exploratory clinical trial took place in Scotland. Thirty women with laparoscopy confirmed superficial endometriosis received a medium sized DCA dose daily for 12 weeks.

The clinical trial ended up with success, some of the women could finally start experiencing life without feeling trapped in their diagnosis. After these exciting results, another bigger clinical study might be on its way. (Ref.)

In the near future, DCA could become the first non-hormonal treatment that treats the cause of this debilitating illness.

Read the DCA for Endometriosis section for the latest updates and details on treatment of endometriotic conditions.

How DCA Works?

DCA has been researched and used in patients for more than 40 years. During this time, the most important features of its work mechanism have been well observed. (Ref.)

Nevertheless, the simple question of how sodium dichloroacetate does its job can leave the majority scratching their heads. To put it in simple words, DCA can help restore the abnormalities of our metabolism back to normal. (Ref.)

The term “metabolism“ can be defined as the sum of all chemical processes within a living organism that keep us alive. Our metabolism determines which substances are useful and nutritious. It also determines which substances are poisonous and need to be removed.

Some diseases tend to change the way our metabolism typically works. These changes lead to the progression of certain sicknesses, as in the case with congenital lactic acidosis, pulmonary arterial hypertension and endometriosis. (Ref.¹), (Ref.²), (Ref.³)

Similarly, abnormal metabolism provides unique advantages for tumor cells. Not only does the imbalance of cellular microenvironment potentiate growth and metastases, but it also helps tumors in avoiding the immune system as well as natural “programmed“ cell death (apoptosis). Both protect us from developing malignant diseases in the first place. (Ref.)

As a rule, metabolism occurs in cells, the smallest units of our body. The cell contains tiny important structures called mitochondria, often referred to as the cellular powerhouses. Why do they earn such a name?

About half our daily caloric intake passes through mitochondria where it gets converted to roughly 90% of the chemical energy that we use for our everyday functions. These structures also detoxify the toxins that tend to accumulate in our body.

Just as importantly, mitochondria signal the old worn-down cells when it’s time to go. This way the body protects itself from defective and malignant cells. Thus, it is safe to assume that mitochondria play a vital role in our metabolism and health. (Ref.¹), (Ref.²)

But what happens when these tiny little structures don‘t work as well as they should? Then the harmony of our biochemistry becomes disrupted, creating the potential for harmful clinical consequences.

For instance, we gain less energy from the nutrients that we get with food, produce more waste products, this leads to increased extracellular acidity, which in turn worsens symptoms.

Not only do we feel extreme fatigue or pain, but also our natural protective mechanisms become suppressed. And that’s just to name a few.

Where does sodium dichloroacetate come into play? DCA has a restorative effect on blocked and malfunctioning mitochondria. Once DCA is administered orally or by injection, it stimulates the enzymes in pyruvate dehydrogenase complex (PDC) by inhibiting Pyruvate dehydrogenase kinase (PDK) within 15-30 minutes of a single dose. (Ref.)

PDK is often overexpressed in the case of tumors, pulmonary arterial hypertension, chronic fatigue syndrome/myalgic encephalopathy and endometriosis. The increased activity of PDK blocks the PDC, which in turn leads to mitochondrial energy failure and dysfunction. (Ref.¹), (Ref.²), (Ref.³), (Ref.⁴)

By suppressing PDK, sodium dichloroacetate restores the function of mitochondria. Subsequently, normal cellular respiration and energy production are resumed. The therapeutic effects linger for 12-24h after taking DCA. If the medication is taken on a regular basis, it leads to resolution of symptoms as well as regression of disease. (Ref.)

As we delve deeper, we realize that it‘s a complex topic as it helps every disease in a different way. To find out more about the condition that interests you the most, please check the detailed articles:

• • DCA for Cancer

• • DCA for Pulmonary arterial hypertension

• • DCA for Chronic fatigue syndrome

• • DCA for Endometriosis

Sodium Dichloroacetate Dosage

• • Oral administration

• • Intravenous administration

There are two main ways to take DCA – one can take it by oral or intravenous administration.

Major advantages of the oral over the intravenous route are – lower drug cost, convenience and no requirement for a health professional or special equipment to give IV Sodium dichloroacetate.

On the other hand, intravenous DCA has its own benefits – reduced risk of adverse reactions, a stronger therapeutic effect and it only needs to be administered two times a week.

Oral Administration

The quickest way to find out the precise daily sodium dichloroacetate dose for a specific condition is by using the new and improved DCAGuide.org calculator that is updated on a regular basis.

The dose is calculated based on a simple mathematical formula.

A kg x B mg/kg = C mg

(Body weight x Dosage strength = Daily DCA dose)

A –  Body weight of a patient. Enter the value without the excess body weight. If possible, use the adjusted ideal body weight based on gender, age and height. To find out your adjusted ideal body weight, visit this site – link.

B – DCA dosage strength. The ordinary DCA dose is 15 mg/kg, the lowest effective DCA dose is 6.25 mg/kg, a high DCA dose is 25-50 mg/kg a day.

C – Daily DCA dose. The medication should be taken twice daily, one half with breakfast and the other half with dinner. Depending on the scheme, breaks from sodium dichloroacetate should be taken on weekends or each third week.

• Cancer and pulmonary arterial hypertension dosing schedule.

For the best results in treating tumors and pulmonary arterial hypertension, use the fourteen days ON, seven days OFF scheme. Then repeat.

This way the best therapeutic effect is obtained. What’s more, an adequate time frame is given for the person to flush excess DCA out of the body before a next cycle to minimize the risk of side effects. (Ref.)

• Chronic fatigue syndrome/myalgic encephalomyelitis and endometriosis dosing schedule.

For the best results with CFS/ME and endometriosis, the five days ON, two days OFF scheme might be the best. The cycle should be repeated every week.

To handle the symptoms of these conditions a more constant DCA intake without bigger pauses is preferred. Alternating one week cycles seems to be the best choice. Sodium dichloroacetate should be taken on Monday – Friday, while a break should be made on Saturday – Sunday.

Intravenous Administration

Usually, patients should be treated starting at a lower dose – 20 mg/kg twice weekly (Monday and Thursday).

If the treatment is well tolerated and no adverse reactions are observed after the first two infusions, one can start increasing the dose by 10 mg/kg each week.

For example, titrate up to 30 mg/kg the second week, up to 40 mg/kg the third week, up to 50 mg/kg the fourth week and so on. If no serious side effects are experienced, the intravenous sodium dichloroacetate dose can be slowly increased up to 80 mg/kg.

Optimal dosing is achieved in a range of 50 mg/kg to 80 mg/kg. The most favorable dose is the one that gives the best benefits yet doesn’t cause significant adverse reactions. This is different for every person and every case should be assessed individually.

The IV DCA should be injected into NaCl 0,9 % 500 ml or Lactated Ringer’s 500 ml bag and administered intravenously over a period of 45 to 60 minutes at a rate of approximately 8-9 mL/min.

Lactated Ringer’s solution is preferred over saline whenever possible.

If possible, after the intravenous DCA dose administration is completed, intravenous Alpha-lipoic acid 600 mg and intravenous Vitamin B1 100 mg infusions should be given.

Following the infusions, the patient should continue taking oral Alpha-lipoic acid and Vitamin B1 supplements daily as usual and without breaks to prevent side effects.

General Principles of Oral and Intravenous Sodium Dichloroacetate  Administration

• You should always begin with a smaller dose. After the first DCA cycle is completed (e.g. a week or three weeks) and when you’re sure that DCA is well tolerated, the dose can be increased to the desired level.

• Vitamin B1 and Alpha-lipoic acid supplements are necessary while taking DCA. They decrease the probability of side effects and their intensity. When DCA is used responsibly and according to the recommendations, the whole experience will most likely be safe and sound. Once you find out the ideal DCA strength that works for you, later on you can try using higher doses, avoid unnecessary discomfort and achieve better results.

For more information, visit the DCA dosage and usage page.

DCA safety and side effect prevention

Sodium dichloroacetate is considered to be a fairly safe treatment. There have been no recorded cases for DCA to be a cause of death. When following the recommendations, it can be used repeatedly without issues. Some patients with congenital lactic acidosis have received DCA treatment continuously for over 10 years. (Ref.)

On the other hand, DCA can cause mild or moderate side effects. Factors that determine the risk are age, genetics, dose strength, dosing schedule and whether protective food supplements are used with the DCA protocol. (Ref.)

The positive side is that if someone experiences side effects, they are temporary and resolve after quitting DCA administration.

Side effects of DCA can be grouped into two categories.

• Neurological.

1) Peripheral neuropathy. It usually manifests as a sensation of tingling (‘‘pins and needles”) in the tongue, hands or feet. If left ignored and untreated, neuropathy can progress to a feeling of numbness or weakness in the hands of feet. This normally takes months to develop. The side effect is reversible and typically resolves in a couple of weeks or months after stopping DCA. Additional supplementation with Vitamin B1, Alpha-lipoic acid and other natural food supplements can prevent/reduce the risk of occurrence. Having neuropathy from previous chemotherapy treatments, diabetes, alcoholism, infections or autoimmune diseases can sometimes increase the risk of developing peripheral neuropathy from DCA. (Ref.)

2) Sleepiness, mental fogginess, confusion or mood changes. These side effects can appear temporarily after DCA administration and usually resolve within a couple of hours. Taking central nervous system affecting drugs such as tetrahydrocannabinol, benzodiazepines, opioids, antipsychotic or other similar medications can increase the risk, especially if adverse reactions from the previous medications are already present. Large doses of intravenous DCA can sometimes cause mild post-infusion sedation. Additional supplementation with Vitamin B1, Alpha-lipoic acid and other natural food supplements can prevent/reduce the risk of occurrence.

• Gastrointestinal and hepatic.

1) Heartburn and nausea. These side effects are temporary, uncommon and usually appear as a result of a direct irritation to the mucous membrane of the upper gastrointestinal tract by Sodium dichloroacetate powder or solution. However, they can still be experienced when taking DCA capsules. If you‘re experiencing stomach discomfort after DCA ingestion, a quick solution would be taking proton-pump inhibitors such as Omeprazole, Esomeprazole or Pantoprazole to fix the problem. The side effect has a higher risk of occurring for those with a history of stomach or digestion problems.

2) Mild asymptomatic liver enzyme elevation. A rare side effect of long-term DCA administration. Blood tests of the patient can show the increase of AST and ALT levels. However, the increase is usually mild and the elevation can be brought back to baseline levels with a temporary break from DCA or using natural supplements for liver health such as milk thistle or essential phospholipids.

If you‘re interested in learning more, read the full article on DCA safety and side effects.

Safe usage

To prevent/reduce the risk of neurological side effects of Sodium dichloroacetate, the most important thing one can do is to take protective supplements. These supplements are also used in hospitals as well as in naturopathic clinics to treat neurological toxicity (etc. diabetic or alcoholic neuropathy).

• Vitamin B1 – thiamine or benfotiamine. (Necessary) (twice a day, with/after breakfast and lunch)

The Vitamin is the main neuroprotective component of the DCA protocol. The metabolism of large Sodium dichloroacetate quantities for a prolonged time can generate excessive compounds and oxidative stress that can harm the cells supporting our peripheral nerves. (Ref.)

To avoid this, Vitamin B1 additional supplementation is crucial. It is speculated that thiamine or benfotiamine help in controlling DCA induced stress on the peripheral nerves in a similar way as with other metabolic neuropathic effects. (Ref.)

Thiamine is the most popular and cheap form of Vitamin B1 supplementation. However, benfotiamine,  a lipid-soluble version of thiamine, reaches the target more efficiently, therefore, has a better neuroprotective effect and requires lower quantities to get the same result. (Ref.1), (Ref.2)

Vitamin B1 supplements also help in preventing other neurological side effects associated with prolonged DCA use.

• Alpha–Lipoic acid. (Necessary) (three times a day, with/after breakfast, lunch and dinner)

α-lipoic acid (ALA) is an antioxidant found in every cell, it is also synthesized in our bodies. The compound is used to prevent and reduce the effects of diabetic neuropathy. (Ref.)

Since the ALA is a strong antioxidant, it serves as a compound that protects the neural tissues against excessive oxidative stress generated by sodium dichloroacetate. (Ref.)

It also means that ALA should not be used 2 days before and 7 days after chemotherapy to avoid diminishing the effects of the medications.

Taking ALA is also not recommended 2 days before and 14 days after radiotherapy.

• Acetyl-L-carnitine. (Recommended) (three times a day, with/after breakfast, lunch and dinner)

Acetyl-L-carnitine (ALC) promotes growth and regeneration of peripheral nerve tissues. Therefore, supplementation of ALC seems a reasonable option for anyone using the DCA protocol. (Ref.)

There are no negative interactions between sodium dichloroacetate and other conventional therapies, which makes it a desirable additional option to treatments like Vitamin B1 and ALA. However, ALC can intensify the effects of Warfarin, a blood thinner.

To find out more details on the correct way to have a safe experience, check the full article about DCA side effect prevention.