Frequently Asked Questions about KetoCitra®.
KetoCitra is a medical food for the daily dietary management of individuals with mild to moderate stages (CKD stages 1-3) of autosomal-dominant polycystic kidney disease (ADPKD) and is intended to be used under medical supervision. KetoCitra is a ready-to-mix drink powder to be dissolved in water and produces a specially formulated solution containing an ionic mixture of D,L-beta-hydroxybutyrate (BHB), citrate, and inorganic electrolytes (potassium, calcium, magnesium).
The BHB delivered with KetoCitra is intended to support the dietary management of cellular metabolic abnormalities in ADPKD. The citrate delivered with KetoCitra is intended to support the dietary management of hypocitraturia in ADPKD. KetoCitra is formulated to deliver an alkaline base load intended to support the balancing of urine pH. KetoCitra is also formulated to deliver calcium and magnesium to manage the dietary absorption of oxalate and inorganic phosphate when taken with meals. KetoCitra is sodium- and sugar-free and formulated to be kidney-safe when used as directed.
Healthcare practitioners and patients should carefully read the latest package insert for directions for use, warnings and contraindications prior to using this product. KetoCitra is not intended for individuals with advanced ADPKD (CKD stages 4-5), hyperkalemia (high potassium levels), or those with severely impaired renal function or impaired electrolyte homeostasis. Prior to using KetoCitra for the first time the blood electrolyte status of the patient should be checked.
Medical foods are neither drugs nor supplements. Instead they are regulated by the US Food and Drug Administration (FDA) as their own category as defined in section 5(b) of the Orphan Drug Act (21 U.S.C. 360ee (b) (3)) and incorporated into FDA regulations.
Medical foods support the nutritional needs of a patient with a disease or condition that are different from the general public, and cannot feasibly be provided simply by modifying food choices in the diet. Because of the need to take all medical and therapeutic aspects of patient care into account, medical foods are intended to be used under medical supervision, including ongoing evaluation of its appropriateness. There is, however, no requirement for a doctor’s prescription. All ingredients used in a medical food must be permitted food additives, or must be Generally Recognized as Safe (GRAS).
Medical foods, dietary supplements, and drugs are all regulated in the US by the Food and Drug Administration (FDA) and serve different purposes. As part of the “food” category, both medical foods and dietary supplements are inherently considered to be safe at dosages used, and therefore do not require pre-market approval. While medical foods must be Generally Recognized as Safe (GRAS), dietary supplements do not have to be GRAS and frequently are not. Dietary supplements are intended to “supplement” the diet of healthy individuals to promote normal structure and function of the body, whereas medical foods are the only food products allowed to be marketed for patients with a disease or condition that requires very specific nutritional support.
In contrast, drugs are typically chemically synthesized, novel compounds that are typically not generally recognized as safe (GRAS). Therefore, prior to market approval, drugs must be clinically tested to prove safety and efficacy against their targeted disease. Many criteria must be met before the FDA will approve a product for drug use. The average cost to bring a new drug to market in the US is approximately $2B ($2,000,000,000) which contributes to very high prices for prescription drugs.
The FDA does not evaluate the safety or health benefits of medical foods prior to marketing, and there is no FDA premarket review or clearance of medical foods. This process is similar to ordinary foods and dietary supplements. Only drugs require premarket approval by the FDA. The ingredients in medical foods, such as KetoCitra, are generally recognized as safe (GRAS). KetoCitra is made in the USA of imported and domestic ingredients under strict cGMP (current Good Manufacturing Practice) standards. KetoCitra is processed and packaged in a NSF cGMP certified and FDA-registered facility. Quality is strictly controlled by testing using in-house and independent, third-party laboratories.
As a medical food, KetoCitra does not require a prescription. However, as a medical food KetoCitra is to be taken under medical supervision. Please visit the KetoCitra homepage for details.
Polycystic kidney disease (PKD) is a genetically inherited form of chronic kidney disease (CKD). The most common form of PKD is “autosomal-dominant polycystic kidney disease” (ADPKD). ADPKD affects over 600,000 people in the US alone and most often runs in families. The hallmark feature of ADPKD is the progressive growth of cysts in both kidneys that leads to organ enlargement, fibrosis and increasing impairment of kidney function. Approximately half of people with ADPKD progress to renal failure, typically in their 50s and 60s. Once the kidneys fail, dialysis or kidney transplantation are required.
ADPKD is characterized by metabolic defects, renal cyst growth, progressive chronic kidney disease and other serious complications. Metabolic abnormalities in renal cells in ADPKD lead to their preference of glucose as an energy source to sustain disease progression over the ketone body BHB (Rowe et al., 2013; Rowe and Boletta, 2014; Sas et al., 2015; Chiaravalli et al., 2016; Riwanto et al., 2016; Magistroni and Boletta, 2017; Padovano et al., 2017, 2018; Podrini et al., 2018; Torres et al., 2019a; Carney, 2020; Cassina et al., 2020; Nowak and Hopp, 2020a, 2020b; Hallows et al., 2021). Additional metabolic abnormalities in ADPKD lead to metabolic acidosis accompanied by acidification of the urine, and low urinary citrate levels (hypocitraturia). Furthermore, individuals with ADPKD frequently have high levels of uric acid (hyperuricemia) and even clinical gout. Altogether, these conditions may increase the risk for kidney stones (nephrolithiasis) and associated renal injury which may further accelerate disease progression (Torres et al., 1988, 1993, 2019c; Mejias et al., 1989; Levine and Grantham, 1992; Grampsas et al., 2000; Errasti et al., 2003; Nishiura et al., 2009; Panizo et al., 2012; Kocyigit et al., 2013; Allison, 2019; Blijdorp et al., 2020).
Individuals with ADPKD may benefit from nutritional management with the goal to address these metabolic abnormalities by raising circulating levels of the natural ketone body BHB to healthy levels, and by supporting a normal, neutral urine pH and normal urine citrate levels.
KetoCitra provides specifically modified nutritional support to address the unique nutrient needs of individuals with ADPKD by increasing circulating levels of the ketone body BHB, normalizing urine pH and urinary citrate, and suppressing the dietary intake of the renal stressors oxalate and inorganic phosphate.
Recent research has shown that ADPKD is a metabolic disease and that the cells affected in ADPKD exhibit distinct metabolic abnormalities that drive disease progression. Individuals with ADPKD have metabolic abnormalities that can be addressed by nutritional management as detailed below. The specific nutritional interventions that are addressed with KetoCitra are provided by supplementing patients with two natural compounds, beta-hydroxybutyrate (BHB) and citric acid (citrate), in a formulation that also delivers beneficial minerals and an alkaline load. Please see the Q&As below for details.
Recent research from several laboratories has established that kidney cells with an ADPKD mutation have a metabolic defect that drives disease progression. These changes in metabolism involve disruption of mitochondrial function, impairment of fatty acid metabolism, and dependence on glycolysis (Rowe et al., 2013; Rowe and Boletta, 2014; Sas et al., 2015; Chiaravalli et al., 2016; Riwanto et al., 2016; Magistroni and Boletta, 2017; Padovano et al., 2017, 2018; Podrini et al., 2018; Torres et al., 2019a; Carney, 2020; Cassina et al., 2020; Nowak and Hopp, 2020a, 2020b; Hallows et al., 2021). These cells become dependent on glucose as their energy source and appear to be unable to efficiently utilize other energy carriers such as fatty acids and ketone bodies. These changes in cellular metabolism resemble the “Warburg effect” that has been known in cancer cells for a long time.
Research has shown that the induction of nutritional ketosis by time-restricted feeding, fasting, or by using ketogenic diets strongly inhibits renal cyst growth and fibrosis in several different orthologous and non-orthologous animal models of PKD (Torres et al., 2019a). These beneficial effects were shown to be mimicked by supplementation with the ketone BHB (Torres et al., 2019a). BHB is the main “ketone body” produced in large amounts by the liver during periods of starvation or fasting. In the absence of starvation or fasting, BHB levels in the blood are very low.
Due to these disease-specific metabolic abnormalities, conventional, carbohydrate-predominant diets consumed by most individuals in industrialized societies may worsen the progression of ADPKD. Serum glucose and serum BHB levels are usually reciprocally regulated by diets. When serum glucose is high (e.g. with standard American high carbohydrate diets), BHB levels are very low, and when BHB levels are high (during starvation), glucose levels are low. Elevated serum glucose levels are a strong predictor of disease progression (as measured by total kidney volume, TKV) in individuals with ADPKD (Torres et al., 2019a). Furthemore, individuals with ADPKD and type 2 diabetes have significantly larger TKV than those with ADPKD alone (Reed et al., 2012). Also, overweight or obesity – which are associated with high glucose and low BHB levels – are associated with faster progression in early-stage ADPKD (Nowak et al., 2018, 2021b, 2021a; Nowak and Hopp, 2020a). These studies suggest that individuals with ADPKD have a need for increased BHB levels.
While it is possible to raise BHB levels by extended fasting or by administering specialized ketogenic diets in animal models, this is very difficult to do – especially in the long term – in human patients with ADPKD. It is well known that adherence to these strict diets is very low, which makes long-term ketogenic dietary interventions unfeasible as therapeutic interventions for the vast majority of patients. This problem can be overcome by supplementing patients with exogenous BHB without the requirement for strict diets. BHB is one of the two main nutritional ingredients in KetoCitra.
Besides renal cystic disease, cardiovascular complications are common in individuals with PKD. While there is limited information on effects of BHB in cardiovascular disease in PKD, growing evidence from numerous recent animal and human studies suggests that ketosis and BHB may be beneficial for patients with cardiovascular disease in general (Yurista et al., 2021).
Individuals with ADPKD have been found to have a deficiency in urinary citrate levels (hypocitraturia) (Lucaya et al., 1993; Grampsas et al., 2000; Nishiura et al., 2009) and also have an abnormally acidic urine pH (Lucaya et al., 1993; Grampsas et al., 2000; Nishiura et al., 2009). A recent study showed that metabolic acidosis (as defined by lower serum bicarbonate) is common in individuals with ADPKD and correlates with a greater risk of worsening kidney function (Blijdorp et al., 2020). Metabolic acidosis is well-known to lead to urine acidification which, in turn, causes hypocitraturia because urinary citrate excretion is partially regulated by urine pH. The mechanistic reasons for these metabolic abnormalities leading to acidic urine and hypocitraturia in ADPKD are still poorly understood.
Low urine pH is generally known as a predictor of chronic kidney disease (Nakanishi et al., 2011).
Low urine pH is a well-known risk factor for forming uric acid kidney stones (Mulay et al., 2014; Pérez, 2018), and hypocitraturia is a well-known risk factor for forming calcium-based kidney stones such as those composed of calcium oxalate (Haghighatdoost et al., 2021). Kidney stones are much more common in ADPKD patients compared with the normal population (Torres et al., 1988, 1993; Levine and Grantham, 1992). Recent research has shown that the concentration of urinary citrate inversely correlates with faster disease progression in individuals with ADPKD (Torres et al., 2019b). Additionally, it was shown that the formation of insoluble microcrystals (such as calcium oxalate and calcium phosphate crystals) in kidney tubules can trigger the formation of renal cysts and leads to accelerated PKD disease progression in animal models (Allison, 2019; Torres et al., 2019b). This effect can be antagonized by supplementation with citrate which causes strong inhibition of renal cyst growth and disease progression in PKD animal models (Tanner, 1998; Tanner and Tanner, 2000, 2003, 2005; Torres et al., 2019b). Nutritional supplementation with alkaline citrate has two principal effects: (1) it raises or normalizes the urine pH, and (2) it raises or normalizes the concentration of urinary citrate (Zuckerman and Assimos, 2009, 2009; Pearle et al., 2014; Holmes et al., 2016). Both effects support the kidneys’ innate defense mechanism to antagonize the precipitation of microcrystals in kidney tubules.
Urinary citrate is known to antagonize the formation of calcium-based crystals (e.g. calcium oxalate and calcium phosphate (Zuckerman and Assimos, 2009, 2009; Pearle et al., 2014; Holmes et al., 2016) and may also antagonize the formation of struvite crystals (Espinosa-Ortiz et al., 2019). Urine alkalinization also inhibits the formation of uric acid crystals (Pak and Adams, 1987; Toblli et al., 2001) and has been shown to facilitate the urinary excretion of uric acid (Kanbara et al., 2010). Individuals with ADPKD have a high incidence of clinical gout (24%) and hyperuricemia (>60%)(Mejias et al., 1989; Errasti et al., 2003; Nishiura et al., 2009; Kocyigit et al., 2013), conditions that are associated with uric acid crystal formation in the kidneys and renal damage (Toblli et al., 2001). Hyperuricemia correlates with faster disease progression in ADPKD (Panizo et al., 2012).
KetoCitra is formulated to deliver citrate and ~50 mEq of alkali load/day to help normalize the urine pH and urine citrate concentration of patients.
KetoCitra is formulated to contain calcium and magnesium (as BHB salts) and is recommended to be taken twice daily with meals (e.g. breakfast and dinner). Calcium and magnesium, when taken with food, are known to bind to oxalate and inorganic phosphate present in food (Hutchison and Wilkie, 2012). For example, oxalate is found in many vegetables such as spinach, and phosphate is found in many processed foods and drinks. If calcium and magnesium are taken together with foods, they will form insoluble complexes with oxalate and phosphate in the gastrointestinal tract and therefore reduce the absorption of oxalate and phosphate (Lemann et al., 1996; von Unruh et al., 2004). Increasing the calcium intake to 1,000-1,200 mg per day is recommended for individuals at risk of recurrent calcium oxalate stones by the American Urological Association and others (von Unruh et al., 2004; Pearle et al., 2014; Holmes et al., 2016). Both oxalate and phosphate are damaging to kidneys (Markowitz and Perazella, 2009; Hutchison and Wilkie, 2012; Holmes et al., 2016; Lumlertgul et al., 2018) and high intake has been shown to worsen PKD disease progression in animal models (Torres et al., 2019c). Even the infrequent ingestion of high-oxalate foods is thought to contribute to increased stone risk and burden on the kidneys (Holmes et al., 2016).
In practice, avoidance of excessive oxalate intake with food is difficult to accomplish because it is often unknown how much oxalate is contained in foods, because there are large differences in the oxalate content of foods as a result of varietal differences and climate effects, and because the absorption of dietary oxalate varies greatly between individuals (Holmes et al., 2016). The same considerations apply to the avoidance of phosphorus intake with food. For this reason, individuals for whom excessive oxalate and phosphorus ingestion may be detrimental, such as people with polycystic kidney disease, could control the absorption of oxalate and phosphorus by ingesting – together with their meals – the calcium and magnesium provided with this medical food.
KetoCitra is formulated to provide 300 mg calcium and 250 mg magnesium (daily intake with 2 servings per day), and it is recommended to take KetoCitra with meals to best suppress the absorption of oxalate and inorganic phosphate.
Several clinical studies have shown that high dietary sodium intake is especially detrimental to individuals with chronic kidney disease including PKD (Chebib and Torres, 2018; Kramers et al., 2020; Ogata et al., 2021). Therefore, dietary sodium restriction is recommended for individuals with PKD. A daily sodium intake of less than 2,300 mg is commonly recommended. Many professionals and organizations (e.g. the American Heart Association) recommend even lower limits (less than 1,500 mg per day) and this amount may be further lowered for people with more advanced stage PKD (Chebib and Torres, 2018; Kramers et al., 2020). It is challenging for most people to implement this level of sodium restriction because sodium is present in almost all processed and restaurant foods, often at very high levels. Americans eat on average about 3,400 mg of sodium per day and the vast majority exceed the recommended intake (Cogswell et al., 2012).
For this reason, KetoCitra is formulated to be sodium-free.
In contrast to sodium, potassium intake is often too low with typical diets in industrialized societies. Our bodies need this essential mineral for healthy cell, nerve, and muscle function. According to the National Institutes of Health, healthy adults need about 4,700 mg of potassium per day. Insufficient potassium intake can increase blood pressure, kidney stone risk, bone turnover, urinary calcium excretion, and salt sensitivity. Emerging data indicate that dietary potassium may be beneficial for patients with CKD and is associated with lower blood pressure, lower cardiovascular risk, and better kidney outcomes (Wei et al., 2020; Ogata et al., 2021).
KetoCitra is formulated to provide additional potassium intake (600 mg daily intake with 2 servings per day) for the management of mild to moderate stages of PKD (CKD stages 1-3).
Since the body regulates its potassium level by excretion through the kidneys, as kidney function declines, plasma potassium levels may become more difficult to regulate. Individuals with severely compromised kidney function often must limit their dietary potassium intake. Therefore, KetoCitra may not be appropriate for individuals with advanced stages of PKD (CKD stages 4 or 5) and a physician must carefully monitor potassium levels before recommending KetoCitra for patients with advanced stage PKD. Excessive dietary intake of potassium can contribute to hyperkalemia, a potentially dangerous condition.
BHB: The general population in industrialized societies rarely, if ever, experiences periods of ketosis. Therefore, serum glucose levels are generally in the “normal” range which is high, and serum BHB levels are generally very low. In ordinarily healthy adults, persistently low BHB levels may be inconsequential. However, as discussed above, in individuals with ADPKD elevated serum BHB may antagonize the detrimental effects of high glucose levels and may beneficially affect disease progression.
Citrate: Most healthy adults have normal levels of urinary citrate and a normal urine pH around pH 6.5 on average. Therefore, most healthy adults have no requirement to increase their nutritional citrate intake or alkalize their urine pH. In contrast, as referenced above, individuals affected by ADPKD frequently exhibit acidic urine pH and hypocitraturia. Therefore, similar to individuals with recurring kidney stone disease, nutritional citrate intake is indicated. Medical foods containing formulations of citrate are available for individuals affected by recurrent stone disease.
Calcium and Magnesium: Most healthy adults can tolerate higher levels of ingested oxalate and phosphate from food sources because their kidneys are able to excrete these substances efficiently. Even if microscopic kidney damage from the excretion of elevated levels of oxalate and phosphate occur occasionally, healthy kidneys are usually able to repair such damage without any overt signs of pathology. However, animal studies have shown that renal injury – including injury caused by oxalate and phosphate – can trigger additional cyst growth and worsen disease progression (Weimbs, 2011; Torres et al., 2019c). Therefore, individuals with PKD should avoid any form of renal insult and are expected to benefit from reducing oxalate and phosphate absorption by consuming KetoCitra with meals.
BHB: People in industrialized societies consume diets with high carbohydrate content. A typical diet consists of ~50-60% carbohydrates, is highly insulinemic and therefore favors the oxidation of carbohydrates over fatty acids. This, in turn, prevents the formation of ketone bodies that serve as an alternative fuel source particularly during periods of starvation. An additional complication is that most people in industrialized societies rarely, if ever, experience periods of ketosis. The reason is the ubiquitous availability of food and dietary habits that lead to frequent food consumption throughout the day (e.g. starting with breakfast and ending with a late-night snack). The only possibilities to increase BHB levels by controlling diet are (1) extended fasting or (2) a high-fat, low-carbohydrate ketogenic diet. While it is technically possible for individuals to commit to drastic lifestyle changes with fasting or ketogenic diets, this is – in practice – impossible for the vast majority of people in the long-term because adherence to ketogenic diets is difficult to accomplish and often poor (Schlundt et al., 1994; Sherman et al., 2000; Desroches et al., 2013; Włodarek, 2019). Furthermore, ketogenic diets may be associated with adverse effects such as gastrointestinal problems, weight loss, hyperlipidaemia, and may also result in vitamin and mineral deficiencies, due to the strict diet regime (Rusek et al., 2019; Jensen et al., 2020). ADPKD is a chronic disease requiring life-long management which makes reliance on ketogenic dietary approaches or extended fasting alone unfeasible.
Citrate: This natural compound found in citrus fruits, such as lemons and limes, is a natural, potent inhibitor of renal crystal and stone formation. Abnormally low levels of citrate in the urine, or “hypocitraturia”, have been strongly associated with the development of kidney stones (Minisola et al., 1989; Holmes et al., 2001, 2016; Zuckerman and Assimos, 2009) and are associated with faster progression of ADPKD (Torres et al., 2019c). Increasing citrate intake is commonly recommended for individuals with recurrent stone disease. However, the practicality of doing this by nutritional means is much harder than it seems. For example, studies have shown that lemonade can increase urinary citrate levels, but one would have to drink up to half a gallon of it daily to get that benefit (Seltzer et al., 1996; Kang David E. et al., 2007). Such a strategy is not practical, especially in the long term. Furthermore, drinking large amounts of lemonade also leads to high sugar/caloric intake, intake of mineral salts that can be incompatible with nutritional requirements of individuals with kidney disease, and increased risk of tooth erosion (Holmes et al., 2001, 2016; Kang David E. et al., 2007; Zuckerman and Assimos, 2009).
KetoCitra is formulated to contain quantities of BHB and citrate aimed at the nutritional management of individuals with mild to moderate ADPKD (CKD stages 1-3) when taken as directed. BHB and citrate in KetoCitra are formulated in a carefully designed blend of mineral salts (potassium, calcium and magnesium). The balance of potassium, calcium, and magnesium is crucial to help support specific nutritional requirements for these electrolytes. The formulation as mineral salts adds an alkali load to the diet which helps to raise and balance the urine pH. This pH balancing effect addresses the known, abnormally low urine pH that is common among individuals with ADPKD (Lucaya et al., 1993; Grampsas et al., 2000; Nishiura et al., 2009). The specific blend of mineral salts is designed to minimize intake of an excess of any of these minerals which is an important consideration for individuals with potentially compromised renal function. KetoCitra is further formulated to be sodium-free because sodium intake is associated with accelerated disease progression in ADPKD (Kramers et al., 2020), and because sodium is known to worsen other common ADPKD symptoms such as hypertension.
This formulation is intended to facilitate the nutritional management of the metabolic abnormalities that exist in individuals with ADPKD. KetoCitra is recommended to be taken with meals and the amount of calcium and magnesium in this formulation are expected to reduce the uptake of the renal stressors oxalate and phosphate that are present in many foods. Dietary uptake of oxalate and phosphate can lead to increased formation of damaging calcium oxalate or phosphate crystals in the kidneys which have been shown in animal studies to aggravate PKD disease progression (Torres et al., 2019b).
ADPKD is a relentlessly progressive disease. While individuals with ADPKD can have very different rates of disease progression, in clinical practice, PKD is not known to improve spontaneously. There are currently no available drugs to prevent, let alone reverse, the progression of ADPKD. As outlined above, recent research has indicated that targeted nutritional management that leads to (1) ketosis (increased BHB) or (2) normalized urine pH and urine citrate can facilitate specific metabolic re-balancing to beneficially affect the progression of PKD in animal models, and these findings are consistent with human clinical observations. The highly sensitive balance between energy substrate source (BHB), citrate and the delicate balance of minerals that support specific nutrient needs to balance urinary pH and bind detrimental oxalate and phosphate cannot be feasibly accomplished by modification of the diet alone as a long-term strategy as is required for this slowly-progressing, chronic disease. KetoCitra is designed to address these unique nutritional requirements, in proper balance considering the stage of disease.
KetoCitra is formulated to be kidney-safe when taken as directed by avoiding sodium and by providing BHB as a blend of mineral salts that avoids excessive intake of any one mineral. These minerals are carefully chosen to provide additional nutritional support. KetoCitra is free of ingredients that may further aggravate kidney function including sodium, fillers, phosphates, whiteners, preservatives, artificial coloring or artificial flavors.
KetoCitra can be taken by itself without any other changes to the normal diet. However, it is recommended to use KetoCitra as part of an overall nutritional management program in conjunction with sensible dietary changes under medical supervision. We recommend to use KetoCitra as part of the specially designed Ren.Nu dietary program for individuals with ADPKD. More information is available here: Ren-Nu.org. Patients may also work with a dietitian or other health practitioner knowledgeable in the latest research on the dietary management of ADPKD. A list of recommended practitioners is available here: https://santabarbaranutrients.com/pages/find-a-practitioner. Santa Barbara Nutrients recommends a team approach between the patient, their doctor and their dietitian.
ADPKD is a heterogeneous disease and there is great variability between individuals. Not only can the rate of kidney disease progression vary greatly but the disease can also manifest in a number of extrarenal complications including cardiovascular disease, liver cysts, hypertension, pain, and intracranial aneurysms. Furthermore, people with ADPKD can be prone to cyst infections or kidney stones. Frequently, individuals with ADPKD may have additional conditions such as diabetes or other metabolic disorders, or any number of comorbidities. Before taking this medical food, it is important that all underlying conditions are known and carefully considered by a physician. In particular, individuals with renal disease may have abnormalities in mineral handling especially those with more advanced disease. Mineral salts contained in this medical food formulation may not be recommended for some patients, or may even be contraindicated. Supervision by a physician is necessary for those taking this medical food as any unexpected health changes can be monitored and readily addressed.
Healthcare practitioners should advise their patients on the recommended daily serving size and frequency depending on the patient’s medical status.
Unless otherwise directed, the recommended adult serving amount is two rounded scoops, taken two times per day, for a total of four rounded scoops (13 g/day). Twice per day, shake or stir vigorously two rounded scoops (approx. 6.5 g) of KetoCitra with 8-16 oz of water and drink slowly (during one hour or more), preferably with a meal. Do not rush drinking KetoCitra. Once reconstituted, any unused mixture should be refrigerated and consumed within 24 hours.
First time users begin with half serving (one rounded scoop, approx. 3.3 g) twice per day for one week to assess tolerance and gradually increase to recommended serving size. In case of gastrointestinal discomfort or any other signs of intolerance, patients should reduce serving size or discontinue use of product, and consult their physician.
Patients should be advised to discontinue use of KetoCitra if any unexpected health changes occur. Physicians should also ensure that only patients with mild to moderate kidney disease (CKD stages 1-3) take KetoCitra. Unless otherwise directed by the physician, KetoCitra is not intended for patients with severely compromised renal function (CKD stages 4 or 5) due to their limited tolerance of mineral salt intake. The physician should monitor the course of the disease by examining the patient and monitoring the blood chemistry, especially minerals (Na, K, Ca, Mg) and markers of renal function (e.g. creatinine, BUN). The frequency of monitoring is at the physician’s discretion and depends on the general health of the patient, the degree of renal function and existing comorbidities.
The typical recommended serving size for a 70kg individual is 5.3g of BHB and 3.5g of citric acid together with an alkaline load of 51 mEq per day which is provided by two servings of KetoCitra per day.
The healthcare practitioner should consider patient body weight, medical conditions, medications, dietary intake, and renal function when determining the serving size and frequency.
The serving size may be increased or decreased depending on the patient’s level of renal function and other medical considerations. Increasing the serving size will provide a higher intake of BHB and citrate but will also lead to a higher intake of minerals. It is recommended that the healthcare practitioner regularly monitors the patient’s blood levels of potassium, calcium and magnesium, and may adjust the serving size of KetoCitra accordingly.
Before taking KetoCitra, a blood panel should be evaluated to ensure that the patient exhibits no abnormal excretion of the minerals supplied in this medical food: potassium, calcium and magnesium. A patient should be in the normal range for potassium, calcium and magnesium or may be deficient. Frequently, individuals with mild to moderate CKD are relatively deficient in potassium and magnesium, and KetoCitra can serve to supplement the intake of these minerals.
The urine pH of the patient should also be monitored. Frequently, individuals with PKD have abnormally low urine pH (e.g. below pH 6) which also leads to hypocitraturia. A target for a normal urine pH is 6.5-7.0 and the serving size of KetoCitra may be adjusted accordingly as long as this does not lead to excessive blood levels of potassium, calcium or magnesium. The patient may wish to utilize the pH indicator paper available from Santa Barbara Nutrients to regularly monitor their urine pH and communicate the values to their healthcare practitioner.
It is not recommended to use more than double the recommended serving size per day.
At the discretion of the physician, and dependent on the health status and stage of kidney disease, patients should be monitored at regular intervals (e.g. every 6 months). In particular, the blood mineral levels (including potassium, calcium, magnesium) and the urine pH may be monitored along with markers of renal function. Should a patient require potassium restriction (e.g. due to compromised renal function) use of KetoCitra should be discontinued.
In most patients, a relatively neutral urine pH is expected to be ideal unless there are other concerns at the physician’s discretion. Chronically low (acidic) urine pH levels frequently occur in individuals with ADPKD leading to chronic hypocitraturia causing an increase in the risk of kidney stones that may accelerate the progression of ADPKD. KetoCitra is designed to help support normal urine pH and normal levels of urinary citrate.
Because urine pH levels can vary depending on the time of day and changes in food intake, it may be advisable for patients to monitor their urine pH frequently at home to observe trends and communicate to their physician. pH indicator paper of the appropriate pH range and suitable for home monitoring is available from Santa Barbara Nutrients.
KetoCitra should not be used together with other urine alkalizing agents such as sodium bicarbonate or potassium citrate unless recommended by a physician.
KetoCitra contains significant amounts of the electrolytes potassium, calcium, and magnesium and is not suitable for individuals with advanced stage chronic kidney disease or other causes of severely impaired renal function or impaired electrolyte homeostasis.
The potassium contained in KetoCitra may increase blood potassium levels in individuals with hyperkalemia. KetoCitra is contraindicated in patients with hyperkalemia (or who have conditions predisposing them to hyperkalemia), as a further rise in serum potassium concentration may become dangerous. Such conditions include chronic renal failure, uncontrolled diabetes mellitus, acute dehydration, extensive tissue breakdown, or the administration of a potassium-sparing diuretic.
Before using KetoCitra, a qualified healthcare practitioner should review the patient’s blood electrolyte levels and determine if there is any predisposition to, or any history of hyperkalemia (high blood potassium level).
KetoCitra is contraindicated in patients with active urinary tract infection. The ability of KetoCitra to increase urinary citrate may be attenuated by bacterial enzymatic degradation of citrate. Moreover, the rise in urinary pH resulting from taking KetoCitra might promote further bacterial growth.
Some people using KetoCitra might experience stomach upset, diarrhea, constipation, or stomach pain. These side effects are more likely to happen in first-time users or when very high serving sizes are used. First-time users should start with half the recommended serving size and only increase the serving size after tolerance is established. Taking KetoCitra with meals and consuming it slowly (during one hour) is recommended.
KetoCitra is not recommended for use by pregnant or nursing women unless recommended by a physician.
Use of KetoCitra may impact how some drugs are metabolized. The healthcare practitioner should review all medications taken by the patient prior to beginning use of the product.
Not to be used as sole-source nutrition.
All ingredients in KetoCitra are Generally Recognized as Safe (GRAS) under their conditions of use. Please refer to the Nutrition Information Table on the label for additional information and the full list of ingredients.
Macronutrient Profile: KetoCitra does not contain fat or protein. An insignificant amount of carbohydrate is contributed by the natural flow agent (soluble corn fiber) and by the natural flavoring (lemon extract and lemon juice concentrate combined with gum acacia). 15 kcal (Calories) of energy per recommended serving (6.5 g) are provided in the form of citrate from citric acid and beta-hydroxybutyrate (BHB), a naturally occurring ketone body used as an energy substrate by nearly all tissues in the body including muscle, brain and heart.
D,L-Beta-Hydroxybutyrate (BHB): KetoCitra contains mineral salt forms of the ketone body BHB as a racemic mixture. KetoCitra provides a blend of mineral salts (potassium, calcium, and magnesium) in order to deliver the maximum amount of BHB while minimizing the total content of any one mineral.
Citrate: KetoCitra provides citrate in the form of citric acid. Upon dissolving KetoCitra in water, the citric acid is partially neutralized by the other ingredients of KetoCitra to provide a balanced overall level of acidity.
Minerals: KetoCitra contains a blend of important electrolytes (potassium, calcium, and magnesium). KetoCitra is formulated to contain only negligible amounts of sodium because dietary sodium intake is associated with accelerated disease progression in ADPKD and other forms of chronic kidney disease (Chebib and Torres, 2018; Kramers et al., 2020). The form of citric acid used in KetoCitra and the natural lemon flavor contribute a negligible amount of sodium. KetoCitra is formulated to provide alkaline base in the form of mineral salts of organic acids.
Flavoring and Sweetener: No artificial flavors or sweeteners are used in KetoCitra. To avoid introducing sugar which would raise blood glucose and insulin and antagonize ketosis, KetoCitra uses a naturally derived sweetener from the leaves of the plant species Stevia rebaudiana. KetoCitra is pleasantly flavored using a blend of dehydrated natural lemon extract and lemon juice concentrate absorbed on gum acacia, a type of natural fiber commonly derived from a species of acacia tree. This fiber acts as a prebiotic compound supporting the growth of potentially beneficial gut bacteria. (Calame et al., 2008).
Soluble Corn Fiber: To preserve the powder consistency and prevent clumping, KetoCitra contains soluble corn fiber, a non-digestible carbohydrate that meets the FDA definition of dietary fiber. This dietary fiber is not digested in the same manner as cornstarch. Instead, it is fermented by microflora in the colon (Carlson et al., 2018; Neri-Numa and Pastore, 2020). The soluble corn fiber used in KetoCitra is non-GMO.
Many ingredients that are commonly found in processed foods or dietary supplements may be renal stressors and potentially harmful to individuals with ADPKD. KetoCitra is specially formulated with kidney-safety in mind and avoids any unnecessary fillers, bulking agents or other artificial or potentially harmful ingredients.
- No artificial flavors.
- No colorings.
- No whiteners.
- No phosphates.
- No preservatives.
Keep container with dry powder tightly closed in a cool, dry place. The powder attracts moisture from the air. Container contains a packet of desiccant to prevent clumping by moisture. Please keep the desiccant packet in the container for the entire time. Do not eat the desiccant.
KetoCitra is made in the USA of imported and domestic ingredients under strict cGMP (current Good Manufacturing Practice) standards. KetoCitra is processed and packaged in a NSF cGMP certified and FDA-registered facility. The facility undergoes frequent, independent auditing by NSF and other quality control organizations, is compliant with 21 CFR 110, 111 and 117 good manufacturing practices and has several certified Preventive Controls Qualified Individuals (PCQIs) on staff per 21 CFR 117. Raw ingredients of the highest quality are carefully sourced, quarantined upon receipt in the manufacturing facility and tested by a combination of in-house and independent, third-party labs prior to processing. The finished products are tested again for heavy metals, microbes, gluten, milk, soy, and the correct amount of active ingredients by in-house and independent, third-party labs prior to release. Climate-controlled, FDA-registered facilities in the USA are used for warehousing and shipping.
The intellectual property underlying KetoCitra was developed at the University of California Santa Barbara. KetoCitra is covered under U.S. Pat. No. 11,013,705 & U.S. and foreign patents pending.
Santa Barbara Nutrients will be working with these programs to try to obtain coverage for patients as much as possible. Currently, it is likely that patients will have to pay out-of-pocket. Note, if you hold a FSA (Flexible Spending Account) or HSA (Health Savings Account), KetoCitra™ can be purchased with your FSA/ HSA card at check-out.
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