Micronutrients (vitamins and minerals) are essential for every structure and function in the human body, including but not limited to the function of the heart, blood vessels, and immune system. Thousands of enzymes in the body require micronutrients for optimal function. Some medications interact with micronutrients, and micronutrients may interfere with the action of medication. The list of those interactions is long, so we will focus on the effect of those most commonly used in kidney disease.
Angiotensin Converting Enzyme Inhibitors
Angiotensin Converting Enzyme Inhibitors (ACEi) are one of the main classes of blood pressure lowering medications in Kidney disease. ACEi (such as lisinopril) have been found in multiple studies to improve outcomes in diabetic and non-diabetic kidney diseases. However, it’s well documented that ACEi can lead to increased levels of potassium in the blood. This elevation may have many serious effects, especially on the heart and the muscles. Furthermore, supplementing with arginine, a precursor of nitric oxide sometimes used to support blood pressure, while taking an ACEi may further increase the risk of increased blood potassium levels.
The use of ACEi also induces zinc deficiency. By binding zinc, ACEi cause an increase in zinc excretion in the urine. Zinc Deficiency has many negative effects on the body, including cardiovascular and metabolic disease risk.
Angiotensin Receptor Antagonists
Another kidney medications and micronutrients interaction involves angiotensin receptor antagonists (ARBs). Just like ACEi, Angiotensin Receptor Antagonists (such as losartan) are one of the most commonly used blood pressure lowering medications in kidney disease. Like ACEi, ARBs also lead to an increase in potassium so electrolyte balance should be monitored closely. Also similarly to ACEi, evidence suggests that ARBs can also lead to zinc deficiency.
Using the powerful antioxidant alpha-lipoic acid (ALA), which can be used as a supplement, has been found to enhance the effects of ARBs by decreasing inflammation and oxidative stress that leads to cardiovascular risk from atherosclerosis.
Diuretics
Diuretics, also known as water pills, are used in kidney patients for blood pressure and fluid control. They are one of the major causes of kidney medications and micronutrients interactions. There are multiple classes of medications that fall into this broad category, and each affects minerals like potassium, magnesium, calcium and various vitamins differently.
For example, hydrochlorothiazide (HCTZ) and furosemide, can lead to potassium and magnesium deficiency so these nutrients are monitored very closely in patients prescribed these drugs. However, their effect on calcium varies. Thiazide diuretics (such as HCTZ) increase calcium retention while loop diuretics (such as furosemide) induce calcium depletion.
HCTZ can increase zinc loss in the urine leading to zinc deficiency. Furthermore, HCTZ can lead to CoQ10 deficiency (by inhibition of NADH oxidase) an antioxidant compound produced in our cells associated with reduced function of cardiovascular muscle and reduced skeletal muscle strength (more about CoQ10 below under statins).
Loop diuretics, including furosemide, have been found to induce deficiency of folate, vitamins B1, B6, and C . Furthermore, drug-induced calcium loss in the urine associated with this class of diuretics can lead to increased risk of bone loss and increased risk for kidney stones.
Beta-blockers
Beta-blockers (BB), such as metoprolol, are commonly used blood pressure reducing medications because they have been found to improve cardiac outcomes.
However, these medications exert their effect while inhibiting enzymes that are dependent on CoQ10 (including NADH-oxidase and succinoxidase). While these medications do not lead to CoQ10 deficiency per se, the concomitant presence of a CoQ10 deficiency for any other reason can lead to greater inhibition of the heart muscle efficiency as well as leading to worsening heart failure.
In addition, BB (especially metoprolol) have been found to decrease the production of melatonin, a compound naturally produced by the body that acts as an antioxidant and sleep inducer. The production of melatonin in the evening as part of our natural sleep-wake cycle induces sleep, and therefore depletion of melatonin causes sleep disturbances. Poor sleep is a major risk factor for progression of kidney disease, diabetes, and hypertension. In patients taking these medications, melatonin supplementation was found to improve sleep quality.
Statins (HMG-CoA Reductase Inhibitors)
Statins, including atorvastatin and simvastatin among many others, are the most commonly used class of cholesterol lowering medications. One of the major drug-induced nutrient depletions of statins is due to the inhibition of the formation CoQ10. Along with insufficient vitamin D blood levels, depletion of CoQ10 along with certain genetic factors is associated with an increased risk of developing a common side effect referred to rhabdomyolysis (muscle breakdown).
CoQ10 is produced throughout the body in the energy powerhouse of the cells. It is a major part of energy production and metabolic process. ”Co” stands for coenzyme, referencing its action in assisting enzymes in an energy production process called the electron transport chain (ETC). The ETC is an essential part of how energy is derived from carbohydrates and fat. Therefore, depletion of CoQ10 not only increases oxidative stress, but also has a significant effect on the function of every organ in our body, and particularly impact the cardiovascular and renal system. .
In addition,statins have been shown to deplete trace elements, including zinc, copper, and selenium. Furthermore, statins while lowering serum fatty acid concentrations (LDL, TG, etc), they also negatively alter the blood levels of important heart-protective polyunsaturated fatty acids (PUFAs while increasing inflammatory arachidonic acid levels. These drug-nutrient interactions are inconsistent from patient to patient, likely due to genetic variations, agent chosen, and dose. Therefore, monitoring lab and symptoms of deficiency or imbalance is ideal.
Metformin
Metformin is used to improve blood sugar by improving insulin sensitivity. Although some kidney patients might be taking metformin, it is not recommended for use in advanced kidney disease due to the increased risk of lactic acidosis.
Metformin is known to decrease the absorption of vitamin B12 by inhibiting the secretion of intrinsic factor, a compound needed to absorb B12 from food. B12 is a water-soluble vitamin and is essential for many processes, including energy production, production of endogenous proteins used for various cell functions including DNA repair, production of blood cells, myelin (cells that make up the nervous system), and some antioxidants. Therefore, supplementing vitamin B12 in patients taking metformin may prevent anemia, maintain brain health, cell production, and support the detoxification pathways.
Insulin
Insulin which is injected to lower blood sugar in diabetics can lead to significant loss of magnesium in the urine. Low magnesium can lead to significant effect on vascular, bone and heart health. In fact, supplementing magnesium in diabetics can improve insulin response.
Proton Pump Inhibitors (PPIs)
Proton Pump Inhibitors (PPIs) are one of the most commonly used drug classes globally, including in patients with kidney disease. Drugs belonging in this class include omeprazole and pantoprazole, which are commonly used for “acid reflux”, decrease stomach acid production leading to nutrient malabsorption and dysbiosis. They can lead to a decrease in calcium, iron, magnesium and vitamin B12. It’s also well-established that they also directly contribute to kidney injury. Despite that, their use remains common and we should remain vigilant in general.
Bottom Line
Many kidney medications can lead to micronutrient deficiencies with negative effect on outcomes and organ functions. The following table helps summarize these for you with general suggestions for supplementation. We recommend that you work with your integrative medicine provider to address complementary therapy to optimize you treatment and nutritional status.
