What is Milk-Alkali Syndrome?
Milk-alkali syndrome is a condition that arises from having too much calcium and alkaline substances in your body. This scenario can lead to increased calcium levels, a shift in the body’s acid-base balance (metabolic alkalosis), and potential damage to the kidneys (acute kidney injury). If not treated, it could lead to severe kidney damage and calcium deposits in the body’s tissues (metastatic calcification).
The condition was first identified in the early 1900s when a doctor named Bertram Sippy developed a treatment formula for stomach ulcers. This formula, known as the ‘Sippy regimen,’ included lots of milk and cream along with substances that neutralize stomach acid like magnesium oxide, or sodium bicarbonate. The treatment worked well, but eventually led to side effects like high calcium levels and a change in the body’s normal acid-base balance. Some patients also exhibited kidney damage.
Though the syndrome became less common with the development of newer medications for stomach ulcers in the 1980s, it is now reappearing. This change may be due to the frequent use of over-the-counter calcium supplements by postmenopausal women to prevent or treat bone loss (osteoporosis). Calcium carbonate is also often given to patients with chronic kidney disease to prevent overactivity of the parathyroid gland (secondary hyperparathyroidism).
Some experts propose renaming the condition to calcium-alkali syndrome to reflect the different causes. Currently, Milk-alkali syndrome contributes to more than 10% of cases of high calcium levels and is the third most common cause of such conditions in hospital patients – after an overactive parathyroid gland and cancer-related conditions.
What Causes Milk-Alkali Syndrome?
Milk-alkali syndrome primarily happens when a person takes too much calcium carbonate, which is present in many over-the-counter medications used to treat conditions like osteoporosis and indigestion. People also take calcium supplements to maintain bone health, particularly if they have chronic kidney disease or are on treatment plans that might weaken their bones, such as prolonged use of corticosteroid medication. Usually, milk-alkali syndrome occurs in people who are consuming more than 4 grams of calcium per day. However, it can also happen if a person consumes as little as 1 gram per day. Drinking milk or milk products along with bicarbonate was once considered a major cause, but isn’t thought to be a significant cause anymore.
Certain medications may also contribute to the chance of getting milk-alkali syndrome. For instance, a type of water pill called thiazide diuretics can play a role since they increase how much calcium your kidneys absorb back into the body, which can cause a fluid and electrolyte imbalance called contraction alkalosis. Certain blood pressure medications (angiotensin-converting enzyme inhibitors) and anti-inflammatory drugs can also decrease how much calcium your kidneys get rid of, which can increase calcium levels in the body.
Milk-alkali syndrome has been reported in pregnant women too. The changes in calcium absorption in the digestive system during pregnancy, high levels of parathyroid-related peptides (hormones that regulate calcium levels), or using calcium carbonate to manage heartburn during pregnancy may be reasons behind this.
Rarely, excessive use of nicotine substitute chewing gum, since it can contain large amounts of calcium, can cause milk-alkali syndrome. In India and Southeast Asia, people who regularly chew betel nut mixed with lime paste containing a significant calcium carbonate component, have also been found to get milk-alkali syndrome.
Risk Factors and Frequency for Milk-Alkali Syndrome
Milk-alkali syndrome is a condition that often leads to hypercalcemia, or high calcium levels, in the United States. A study showed that this syndrome was responsible for 12% of hypercalcemia cases in hospitalized patients – making it the third leading cause after hyperparathyroidism and malignancy. This condition is more common in areas where people consume large amounts of calcium carbonate, or where betel nut chewing is common, such as in India and Southeast Asia.
In the past, the syndrome was typically found in men who consumed milk and absorbable alkali to treat peptic ulcer disease. Nowadays, it’s more commonly found in post-menopausal women who consume high amounts of calcium carbonate products.
Signs and Symptoms of Milk-Alkali Syndrome
Milk-alkali syndrome is a condition that is usually identified when trying to rule out other causes of high calcium levels in the body. Crucial steps in diagnosing this condition include getting a detailed patient history and conducting a thorough physical exam. It is important to know if the person has been taking any over-the-counter medications that contain calcium as numerous such preparations are available. Most people with this condition don’t have evident symptoms; issues like high calcium levels, imbalances in bodily fluids or electrolytes (alkalosis), and kidney damage are often found incidentally. However, some may experience symptoms due to excessive calcium in their blood. These can include neurological problems like changes in mental status, headaches, vertigo, dizziness, and fatigue. Gastrointestinal issues like nausea, vomiting, loss of appetite, and constipation may also occur. Genitourinary symptoms can include increased urination and kidney stones, and some people might also feel palpitations.
During a physical exam, the person might show signs of reduced deep tendon reflexes and decreased muscle strength and tone due to high calcium levels. Mental health evaluations could reveal signs of depression, anxiety, or cognitive problems due to this condition. Metabolic alkalosis, which is another aspect of this condition, can potentially decrease breathing rate and central respiratory drive, although this effect is usually minimal.
Historically, milk-alkali syndrome progresses in three stages, generally associated with the duration and timing of exposure to antacids containing calcium:
- Acute Toxemic Phase: This phase typically occurs within a month of starting on the antacid regime. Symptoms during this phase are similar to those seen in acute high calcium conditions, such as headache, vertigo, dizziness, nausea, vomiting, and loss of appetite.
- Subacute Phase (also known as Cope syndrome): During this phase, features of both acute and chronic high calcium conditions are observed.
- Chronic Phase (also known as Brunett syndrome): People that have been on the milk and alkali regime for years usually reach this phase, which is characterized by symptoms of long-term high calcium conditions. These symptoms may include excessive urination, excessive thirst, itching, shaking, and psychosis.
In the chronic phase, an abnormal deposit of calcium may be observed in tissues and organs. Conditions like Band keratopathy (a disease affecting the eye) and nephrocalcinosis (a kidney condition) are common in this phase. There may also be calcium deposit in various other parts like the liver, central nervous system, tissues around the joints, under the skin, adrenal glands, bones, and lungs.
Testing for Milk-Alkali Syndrome
When high calcium levels are found in your blood, it’s usually discovered accidentally during a routine blood test. Another test that might be done is an arterial blood gas analysis, which can reveal a condition doctors call “metabolic alkalosis”. This test is particularly important because it can provide useful information about how well your lungs and kidneys are working to maintain your body’s pH balance.
Your doctor might also want to check your serum albumin levels, especially if you also have high calcium levels. Albumin is a type of protein made by the liver that helps keep fluid from leaking out of your blood vessels. A low albumin level could indicate a problem with your liver or kidneys or that you are not getting enough protein in your diet.
In addition to albumin, your doctor may measure parathyroid hormone (PTH) levels. PTH helps control calcium, phosphorus, and vitamin D levels within the blood and bone. When PTH levels are low, as in milk-alkali syndrome, it could point to primary hyperparathyroidism or familial hypocalciuric hypercalcemia – conditions where the body produces too much parathyroid hormone, causing high calcium levels in the blood.
Other tests can be used to eliminate other causes of high calcium levels. These tests can check for conditions like hyperthyroidism or multiple myeloma. They can also check levels of a substance called parathyroid-related peptide and the active form of vitamin D in your blood. Normal levels of these substances can help rule out certain types of cancer and a condition called sarcoidosis, which can cause high calcium levels.
Radiological investigations, including chest X-rays, may be done to further eliminate potential causes of high calcium levels, like cancer or sarcoidosis. If there’s a problem with your kidneys, additional imaging of the kidneys may be necessary – this can provide helpful information about the severity of any kidney damage.
Finally, an electrocardiogram (ECG) could be included to check for any potential heart rhythm problems. High levels of calcium in the blood can cause changes to the heart’s normal rhythm, including a shortening of a specific segment on the ECG known as the QT interval or the creation of what’s known as J waves.
Treatment Options for Milk-Alkali Syndrome
If you have mild hypercalcemia – higher than normal levels of calcium in your blood – the primary step is often to stop taking the cause, usually a supplement like calcium carbonate. Removal of the source can quickly help to rectify the out of balance calcium level. If the hypercalcemia is severe, you’ll need to be managed in a hospital setting.
Upon hospital admission, calcium supplements are stopped and you’ll receive fluids through an intravenous (IV) drip, typically using a type of saltwater solution called normal saline. This helps treat the high calcium levels and corrects any fluid loss in your body. The rate of fluids given through the IV can vary and will be carefully calculated based on your age, kidney function, other health conditions, and severity of hypercalcemia.
Loop diuretics, a type of water pill which includes drugs like furosemide, may be used to boost calcium excretion through urine. These are generally used in severe hypercalcemia cases and caution is needed as they can make existing fluid loss worse.
Some patients may have temporary low calcium levels (hypocalcemia) with a corresponding rise in parathyroid hormone levels after being given loop diuretics. This is usually mild and temporary, and typically doesn’t require treatment. Oral calcium citrate can be considered, but calcium carbonate should be avoided. Bisphosphonates, a type of medication used to treat bone diseases, are generally not recommended for those with milk-alkali syndrome (a condition caused by taking too much calcium and absorbable alkali) because they can cause prolonged low calcium levels.
However, a specific type of bisphosphonate called Pamidronate has been found to be effectively used in some situations.
What else can Milk-Alkali Syndrome be?
The milk-alkali syndrome is a condition that needs to be diagnosed by ruling out other causes first. Several diseases and health conditions can lead to high calcium levels in the body, which is a characteristic of the milk-alkali syndrome.
Conditions resulting in high calcium levels and increased parathyroid hormone levels, that should be considered are:
- Hyperparathyroidism (primary or tertiary)
- Familial hypocalciuric hypercalcemia
- Acquired hypocalciuric hypercalcemia
Conditions that cause high calcium levels with a normal level of parathyroid hormone, similar to milk-alkali syndrome, include:
- Cancer
- Hyperthyroidism
- Blood cancers
- Lack of physical activity
- Hypophosphatasia (a rare inherited disorder)
- Sarcoidosis and other diseases causing inflammation
Last but not least, the following drugs or excessive intake of certain vitamins can also lead to high calcium levels:
- Thiazide diuretics
- Lithium
- Vitamin D
- Excessive vitamin A
What to expect with Milk-Alkali Syndrome
The outcome for milk-alkali syndrome is usually positive, since it can be easily solved by stopping the use of calcium supplements and absorbable alkalis – substances that neutralize stomach acid. The risk or extent of health problems from the disease strongly depends on how severe and long-lasting the high calcium levels in the blood are (hypercalcemia).
If milk-alkali syndrome is identified early and treated correctly, the likelihood of developing further complications can be greatly reduced, providing a good outlook for the patient. However, if the condition becomes long-term (chronic), it can result in permanent damage due to widespread calcium deposits in the body. This highlights the importance of recognizing and treating the condition early.
Possible Complications When Diagnosed with Milk-Alkali Syndrome
The milk-alkali syndrome doesn’t usually cause problems in the long run, since it can be easily treated in most cases, often by simply stopping to consume the substance causing the problem. However, there are times when it can lead to lasting damage to the kidneys, even when the cause has been removed from a person’s diet. Some reported cases show that people have had high creatinine levels (more than 1.5 mg/dL), indicating kidney problems, and some have even experienced kidney failure in the period after their initial treatment.
Side effects related to the nerves, including feeling very drowsy or even going into a coma, have also been observed in patients who have more than 15 mg/dL of calcium in their blood. This is especially common in older adults, people who’ve had long term issues with their kidneys, and those who are on dialysis (a treatment for kidneys that aren’t working properly). There have also been instances when milk-alkali syndrome has led to continuous epileptic seizures due to high calcium levels in the blood.
Common Complications:
- Permanent kidney damage
- Weakened kidneys (indicated by high creatinine levels)
- Kidney failure even after stopping intake of the causative agent
- Neurological issues like extreme drowsiness and coma
- Risk of complications in older adults, those with long-term kidney disease, and people on dialysis
- Status-epilepticus (continuous epileptic seizures) due to high calcium levels in blood
Preventing Milk-Alkali Syndrome
More people are becoming aware of the importance of calcium, and the easy access and frequent prescription of calcium supplements are leading to more cases of a condition called milk-alkali syndrome. Milk-alkali syndrome is a medical condition that results when a person’s body has too much calcium. Patients should be informed about how this condition happens and the symptoms of having too much calcium in the body. It’s important for patients to be mindful of the supplements they are taking and what’s in them. In many cases, patients may be taking in more calcium than they realize because they’re getting it from multiple sources. Patients should have a clear understanding of the recommended dosage for supplements, as well as the dosages that could be harmful. This is especially important for patients with chronic kidney disease because they have a higher risk of developing dangerously elevated levels of calcium in their blood and a condition called metabolic alkalosis, which is a chemical imbalance in the body. That being said, patients who are diagnosed early with milk-alkali syndrome should feel reassured. This condition is usually reversible and often has a good outcome if the source of the excess calcium is identified and removed.
