Phenylbutyrate (4-PBA) For ALS (Amyotrophic Lateral Sclerosis): Dosage, Supplements, Side Effects, and Success Stories

Phenylbutyrate, a monocarboxylic acid characterized by the presence of a phenyl group attached to the fourth carbon of butyric acid, is known for its role as a histone deacetylase inhibitor. This distinct capability lends it the potential to combat cancer. Phenylbutyrate has been shown to thwart cell growth, invasiveness, and the spreading of cells, while simultaneously triggering programmed cell death in glioma cells, a type of tumor originating in the brain. Phenylbutyrate interferes with protein isoprenylation—a post-translational modification critical for various cellular processes. It diminishes the concentration of glutamine in the blood, enhances the production of fetal hemoglobin by promoting the transcriptional activity of the γ-globin gene, and it influences the activation of human Peroxisome Proliferator-Activated Receptor Gamma (hPPARγ), a receptor involved in the regulation of fatty acid storage and glucose metabolism.

Phenylbutyrate is a medicine that changes its form inside the body. When you take it, it gets transformed into a substance called phenylbutyryl-CoA, and then your body breaks it down further to turn it into phenylacetate. This mainly happens in your liver and kidneys. What makes phenylacetate special is that it grabs onto another substance, glutamine, and together they form something new called phenylacetylglutamine. This new substance is then removed from your body when you pee. It carries the same amount of nitrogen as another substance called urea, which means it can help get rid of excess nitrogen in your body, much like urea does.

When you take a tablet or powder form of sodium phenylbutyrate , it starts getting into your bloodstream in about 15 minutes, and it's usually most concentrated in your blood after about an hour. Additionally, it changes into its active form, phenylacetate, within approximately 30 minutes.

How Sodium Phenylbutyrate Works?

Sodium phenylbutyrate is a medication that turns into phenylacetate in the body. Phenylacetate then combines with a molecule called glutamine to create phenylacetylglutamine. This substance gets removed from the body in urine, taking extra nitrogen with it.

When people take sodium phenylbutyrate, it changes into phenylacetate after they swallow it. Phenylacetate links up with something called phenylacetyl-CoA and then attaches to glutamine, making phenylacetylglutamine. This new substance, which contains two nitrogen molecules just like urea, is then filtered out by the kidneys. This helps get rid of excess nitrogen, which is especially useful when the body can't process nitrogen properly.

How to Use Phenylbutyrate (4-PBA)

If your doctor prescribes Sodium Phenylbutyrate, it's important to take it exactly as they tell you. Make sure to follow their instructions on how much to take and what you should eat. Don't change the dose on your own, and if your weight changes, let your doctor know because your dose might need to change too. Take the medicine with food so your body can absorb it better. If it comes in oral pellets, use the measuring device that comes with it and don't chew or dissolve the pellets. Keep the medicine stored in the right conditions and throw away any pellets that haven't been used after 45 days. If you forget to take a dose, take it as soon as you remember, unless it's almost time for your next dose. In that case, skip the missed dose and don't double up to catch up.

Remember, Sodium phenylbutyrate isn't for quickly lowering ammonia levels in the blood. Tell your healthcare provider about your full medical history, especially if you have heart problems, high blood pressure, diabetes, can't tolerate fructose, or have trouble absorbing sugars in your diet. Also, talk to them if you are pregnant or breastfeeding. This medication is for people with certain enzyme issues that affect the urea cycle, which is a process in the body that helps get rid of ammonia. If someone has a problem with this process, Sodium Phenylbutyrate can help manage the condition by helping the body remove ammonia in a different way. It's important to keep regular appointments with your healthcare provider to check how the treatment is working and to discuss any side effects or concerns you may have. Remember to keep the communication open with your healthcare team about any changes in your health or symptoms while taking this medication.

Is 4-PBA Toxic?

About one in four women who have periods experienced either a stop in their periods or irregular periods. Other issues reported by all patients included a decreased appetite in 4%, and some had problems with their body odor. In addition, 3% did not like certain tastes they once did. Less common side effects, affecting less than 2% of patients, were stomach pain, gastritis, nausea and vomiting, constipation, bleeding from the rectum, and ulcers in the stomach or intestines. A few people also had pancreatitis, a bone marrow problem called aplastic anemia, unusual bruising, heart rhythm issues, swelling from fluid buildup, a kidney problem involving acid levels, feeling depressed, skin reactions like rashes, headaches, fainting, and gaining weight. These were rare but happened at least once. (Ref. )

When it came to lab results and other side effects, there were some notable changes. Fourteen percent of people had too much acid in their blood, 7% had too much alkaline and chloride in their blood, and 6% had low phosphate levels. A small number, 2%, had high levels of uric acid and phosphate, while 1% had too much sodium and not enough potassium, with 11% showing low levels of a protein called albumin. Other findings included 3% of patients showing lower total protein levels, a 6% increase in a liver enzyme called alkaline phosphatase, and a 4% rise in liver enzymes known as transaminases. Also, 1% had too much bilirubin, a substance that can indicate liver issues.

When it came to blood, 9% of the patients were anemic, meaning they had a lower than normal number of red blood cells. White blood cell counts were off in 4%, with some having too few and others too many. Platelet counts – the cells that help blood clot – were also irregular, with 3% having too few and 1% having too many.

Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis, also known as ALS, is a rare group of brain diseases that affect the nerves (neuron cells) which help us move the muscles we can control, such as those we use for chewing, walking, and talking. This disease gets worse over time and unfortunately, there's no cure nor a way to slow it down or reverse the damage it causes. (Ref. )

ALS is part of a broader category of illnesses called motor neuron diseases. These happen when motor neurons (nerve cells that carry messages from the brain to our muscles) start to fall apart and eventually stop working. These important nerve cells not only help us do things on purpose but also send vital signals from our brains to our muscles.

When the brain tells a muscle to move, it sends the message to upper motor neurons, which then pass it on to lower motor neurons in the spinal cord and then finally to the muscle itself. In people with ALS, both sets of motor neurons—upper and lower—break down or die, which means they can't send these signals anymore. Without these signals, muscles can't move and start getting weak. They can also twitch uncontrollably, and eventually, the muscles shrink down because they're not being used. Over time, the connection between the brain and the muscles fades, and a person loses the ability to make their muscles move on purpose.

The first signs of ALS can be things like muscle weakness or tightness. Slowly, the disease affects all the muscles that a person can control, leading to a loss of strength and the ability to speak, eat, move, and even breathe on their own. Most people who have ALS pass away from not being able to breathe, which usually happens between 3 to 5 years after the first signs of the disease appear. Yet, around 10% of those with ALS live for 10 years or longer. (Ref. )

Phenylbutyrate and ALS?

A new drug called AMX0035 , which is a combination of sodium phenylbutyrate and taurursodiol, has been proposed to the U.S. Food and Drug Administration (FDA) to help treat amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease.?(Ref. )

AMX0035 comes in the form of a pill and works by avoiding damage to nerve cells that is typical in ALS. This could slow down the worsening of the disease.?

This request for approval is backed by results from a study called the CENTAUR trial, and its extension. The CENTAUR trial was a well-organized study where 137 ALS patients were split into two groups; one group received the real drug and the other received a placebo, which is a treatment with no active drug. They took the medicine or placebo every day by mouth or through a feeding tube, starting once daily and going twice daily if they could handle it. After six months, the group taking AMX0035 showed a slower decline in their ability to function compared to the placebo group. (Ref. )

Furthermore, an additional study followed 95 patients from the CENTAUR trial over three years to check the long-term safety of AMX0035. Those who had begun with AMX0035 in the first trial lived longer, on average, than those who had the placebo. Specifically, the AMX0035 group had a 44% reduced risk of death and lived about 25 months on average, whereas the placebo group lived about 18.5 months on average. (Ref. )

What is the Correct Phenylbutyrate 4-PBA Dosage?

Each patient will need a different amount of this medicine, so it's important to follow what your doctor tells you or to use the amount suggested on the bottle's label. We're giving you an idea of the usual amounts people take, but please remember that your specific dose might be different. Don't make any changes unless your doctor gives you the go-ahead.

How much you need to take of this medicine depends on how strong it is. It also depends on how many times a day you need to take it, how long you wait between doses, and how long you need to take it overall. All of this is based on the health issue you're treating with the medicine.

For managing urea cycle disorders, this is how much medicine people commonly take:

Phenylbutyrate Dosage

- Adults and kids over 20 kg: How much you take is tailored to your size, something your doctor will figure out. Usually, you take 9.9 to 13 grams for every square meter of your body's surface, and you spread this amount over 3 to 6 doses per day. But you usually won't take more than 20 grams in a day.

- Kids under 20 kg: How much they take depends on their weight, and the doctor decides this too. Generally, they take 450 to 600 milligrams per kilogram of their weight each day, split into 3 to 6 doses. But they typically won't have more than 20 grams in a day.

Buy only the best quality 4-PBA, some recommended suppliers are:

• https://www.purepba.com/
• https://www.canchema.com/
• https://www.sigmaaldrich.com/US/en/substance/sodiumphenylbutyrate186181716127

Phenylbutyrate Powder Form Dosage Solution:

- Adults, teens, and children over 20 kg (44 pounds or more): The amount you'll take is based on your size, which your doctor will determine. Usually, you'll take your dose 4 to 6 times during the day. But you generally won't have more than 20 grams in a day.

- Children weighing less than 20 kg (44 pounds): The dose is worked out based on their weight by the doctor. They usually take 450 to 600 milligrams per kilogram of their weight every day. This is divided equally and taken 3 to 6 times a day. But like the other forms, it's usually no more than 20 grams a day.

Buy only the best quality 4-PBA, some recommended suppliers are:

• https://www.purepba.com/
• https://www.canchema.com/
• https://www.sigmaaldrich.com/US/en/substance/sodiumphenylbutyrate186181716127

Sodium Phenylbutyrate Liquid Suspension Form:

- Adults and children over 20 kg: The dose is tailored to your body size, as determined by your doctor. Commonly, the dose is 9.9 to 13 grams per square meter of body surface each day, and this is spread out into 3 to 6 doses throughout the day. But generally, you won't take more than 20 grams per day.

- Children under 20 kg: Taking the liquid suspension is generally not recommended for this group.

Buy only the best quality 4-PBA, some recommended suppliers are:

• https://www.purepba.com/
• https://www.canchema.com/
• https://www.sigmaaldrich.com/US/en/substance/sodiumphenylbutyrate186181716127

Sodium Phenylbutyrate Tablet Form:

- Adults, teens, and children over 20 kg (about 44 pounds or more): The amount of tablets you'll take is based on your body size and your doctor will decide the exact dose. You normally take the tablets 3 times a day. The total daily dose usually should not exceed 20 grams, which is about 40 tablets.

- Children weighing less than 20 kg (about 44 pounds): It's generally not recommended for them to use the tablet form.

Buy only the best quality 4-PBA, some recommended suppliers are:

• https://www.purepba.com/
• https://www.canchema.com/
• https://www.sigmaaldrich.com/US/en/substance/sodiumphenylbutyrate186181716127

Sodium Phenylbutyrate 4-PBA Side effects and safety

It's really important for your doctor to regularly check on you to make sure the medication sodium phenylbutyrate is working right. You might need blood and urine tests to look for any negative effects.

This drug can sometimes cause issues with your nervous system. If you start to feel confused, get headaches, feel lightheaded, nauseated, sleepy, tired, or if you throw up, you should tell your doctor straight away.

In an emergency—like if something goes wrong because of your urea cycle disorder—you should be ready. Wearing a medic alert bracelet all the time is smart, and also keep a card in your wallet or purse that says you have this condition and a list of all drugs you take.

Don't start any new medicines without talking to your doctor first, whether they're prescriptions, over-the-counter drugs, or even vitamin or herbal supplements.

Medicine can have good effects, but sometimes there may be unwanted ones too. Not everyone gets these side effects, but if they happen, you might need to seek medical help.

Some Common Side Effects Are:

- Delayed menstrual cycles

- Pain in your lower back, side, or stomach

- Mood or mental changes

- Muscle pain or twitching

- Nausea or vomiting

- Feeling nervous or restless

- Swelling in your feet or lower legs

- A bad taste in your mouth

- Feeling unusually tired or weak

Less Common Side Effects Include:

- Absent or irregular periods

- Black, tarry stools

- Bleeding gums

- Feeling bloated

- Blood in your urine or stools

- Bone pain

- Burning, numbness, tingling, or pain in your hands, arms, feet, or legs

- Chest pain or tightness

- Chills

- Constipation

- Coughing

- Dark urine

- Feeling down

- Dizziness

- Fainting

- A fast heartbeat

- Feeling sad or empty

- Fever

- Headache

- Heartburn

- Feeling irritable

- Joint pain, stiffness, or swelling

- Large, flat, blue or purple patches on the skin

- Loss of appetite

- Not feeling interested in things or not enjoying things you usually do

- Mood swings

- Muscle cramps or twitching

- Numbness or tingling in your hands, feet, or lips

- Pains in your stomach, side, or abdomen that may spread to your back

- Painful or difficult urination

- Pinpoint red spots on the skin

- Rectal bleeding

- Seizures

- Feeling like you have pins and needles

- Severe or ongoing stomach pain

- Sore throat

- Sores, ulcers, or white spots on your lips or in your mouth

- Sharp pain

- Skipped menstrual periods

- Swelling in your feet or lower legs

- Swollen or painful glands

- Trouble breathing

- Difficulty concentrating

- Trouble sleeping

- An uneven heartbeat

- Unusual bleeding or bruising

- Yellowing of your eyes or skin

Rare Side Effects Might Be:

- A dry mouth

- An unusually fast, slow, or irregular heartbeat

- Feeling very thirsty

- Swelling of your face

- Gaining weight without a clear reason

- A weak pulse

There are some side effects that are not usually serious. Your body might just be getting used to the medicine, and these issues could go away on their own. But if they don't go away or they really bother you, you should talk to your healthcare provider. They might give you tips on how to prevent or reduce these effects. Less common ones are?

- Body odor

- A burning sensation in the chest or stomach

- A decrease in appetite

- An increase in weight

- Skin rash

- Stomach upset or pain

There Are Also Side Effects That Might Happen, But We Don't Know How Often They Occur:

- A change in how things taste

- Losing your sense of taste

Sometimes people might experience other side effects not listed here. If you notice anything else that's not normal, it's a good idea to talk with your healthcare professional about it. They can help figure out if it's related to the medication and what to do about it.