What is Hypoglycemia?

Hypoglycemia, or low blood sugar, can cause significant and life-threatening consequences if not treated immediately. Hypoglycemia is often caused by overly aggressive treatment with glucose-lowering drugs in diabetic patients—glucose levels drop too low, causing an episode of hypoglycemia. Hypoglycemia can also be reactive; if glucose is absorbed too rapidly after eating, it can cause sudden spikes in insulin levels in people with diabetes or prediabetes, which then cause glucose levels to plummet.

For patients with diabetes, proper dosing of medications is essential to avoid hypoglycemic episodes. Also, maintaining healthy glucose levels is a proactive step that is important for everyone.

Natural interventions such as fructooligosaccharides and Irvingia gabonensis can help slow glucose absorption to prevent the sudden spikes and dips associated with hypoglycemic episodes.

What Causes Hypoglycemia?

• Iatrogenic hypoglycemia: caused by diabetes medications that reduce blood glucose levels
• Reactive hypoglycemia: insulin hypersecretion after meals (common in people who have undergone gastric bypass)
• Other causes such as fluoroquinolone use, Addison’s disease, polycystic ovary syndrome, and advanced liver or kidney disease

What are the Signs and Symptoms of Hypoglycemia?

• Shaking or tremors
• Pounding heart
• Anxiety
• Sweating
• Tingling
• If insufficient glucose is available in the brain, warmth, confusion, or drowsiness may occur.
• Prolonged hypoglycemia can lead to coma and/or death.

Note: Symptoms of hypoglycemia do not always manifest; some people may be unaware they are hypoglycemic until glucose levels drop dangerously low. Proper glucose level monitoring is essential in those with diabetes or prediabetes.

What are the Conventional Medical Treatments for Hypoglycemia?

• Immediately restoring normal blood glucose levels by administering glucose
• Long-term management to prevent future episodes, such as changing medications or dosing

What Novel Therapies Exist for Hypoglycemia?

• Implantable continuous glucose monitoring devices
• Improving patients’ awareness of hypoglycemia with medications such as naltrexone or fluoxetine
• Treatment with acarbose to slow the breakdown of carbohydrates into glucose

What Dietary and Lifestyle Changes Can Help Manage Hypoglycemia?

• Increase intake of dietary fiber to slow the rate of carbohydrate absorption
• Eat less refined carbohydrate-rich foods
• Eat several small meals and snacks throughout the day
• Do not drink alcohol without eating

What Natural Interventions Can Help Manage Hypoglycemia?

• Fructooligosaccharides. Fructooligosaccharides are prebiotic fibers found in many plant foods that can help stabilize post-meal glucose levels. One study demonstrated that supplementation with fructooligosaccharides significantly improved glucose profiles and reduced episodes of hypoglycemia.
• Chromium. Chromium supplementation can help control blood glucose levels and improve the metabolism of carbohydrates.
• Green coffee bean extract. The extract from unroasted coffee beans and a derived compound, chlorogenic acid, have been shown to temper post-meal glucose spikes, reduce glucose absorption, and inhibit the intestinal enzyme alpha-glucosidase.
• White bean extract. White bean extract blocks alpha-amylase, an enzyme responsible for breaking down sugars. Blocking this enzyme slows the rate of glucose absorption.
• Irvingia gabonensis. African mango tree extract ( Irvingia gabonensis ) also blocks alpha-amylase . This extract may also help with weight loss.
• Seaweed extracts. Extracts from kelp and bladderwrack inhibit alpha-amylase and alpha-glucosidase, the enzymes that help with breaking down dietary starches.
• L-arabinose. An indigestible plant compound, L-arabinose inhibits the enzymatic activity of sucrase, the enzyme that breaks down sucrose. L-arabinose can therefore prevent the spike in blood sugar that follows sugar-rich meals.

Glucose is a chief energy source for cells throughout the body. However, too much or too little of it can cause serious adverse consequences (Berber 2013; Shrayyef 2010).

Despite the rampant, interrelated epidemic of obesity and type 2 diabetes, most Americans remain regrettably unaware of the long-term damage from chronically elevated glucose levels, also called hyperglycemia. Conditions like kidney damage, nerve damage, and often irreparable damage to the eyes that result from continuously elevated glucose take time to manifest (Campos 2012).

However, even less well-appreciated than the long-term risks due to chronically elevated blood sugar is that very low blood sugar, termed hypoglycemia, can cause significant, acute, life-threatening consequences if not treated immediately (Berber 2013).

Blood sugar levels at or below 40 mg/dL characterize severe hypoglycemia (Desouza 2010; Tsai 2011; Carey 2013; Lacherade 2009). Low blood sugar levels in this range can cause a variety of symptoms ranging from weakness, sweating, fast heart rate, and tremors to confusion, irritability, or in severe cases, even coma and death (Sprague 2011; Berber 2013; McCrimmon 2012).

With overly aggressive pharmaceutical treatment, patients with diabetes, both type 1 and type 2, are at risk for episodes of severe hypoglycemia. For type 1 diabetics, hypoglycemia can result from overtreatment with injectable insulin (Cryer 2010). In fact, hypoglycemia represents a serious barrier to successful management of type 1 diabetes; about 2-4% of acute death among type 1 diabetics are likely caused by hypoglycemia (Briscoe 2006; Cryer 2008). Type 2 diabetics can also develop hypoglycemia as a result of overtreatment with glucose-lowering drugs, in particular the class of drugs known as sulfonylureas (Kalra 2013; Bodmer 2008).

In contrast to the potentially devastating consequences of over-aggressive drug treatment of hyperglycemia in diabetes patients with insulin and/or sulfonylureas, reactive hypoglycemia (or postprandial hypoglycemia) is a phenomenon in which blood sugar levels drop a few hours after eating (UW Health 2013). Typically, reactive hypoglycemia strikes people who are not diabetic but nevertheless manifest less than optimal glucose control (eg, individuals with prediabetes). These individuals are more prone to reactive hypoglycemia than healthy people. Reactive hypoglycemia is also more common in people who have undergone gastric bypass surgery for severe obesity. The drop in blood sugar level (or “crash”) observed in reactive hypoglycemia is the result of an overly exaggerated insulin spike following ingestion of carbohydrate, with a subsequent reactive plunge in blood sugar level due to the exaggerated spike in insulin (Brun 2000; Roslin 2011; Middleton 2012; Bell 1985).

There are other, less common causes of hypoglycemia as well. For example, pancreatic tumors that result in excess insulin being released into circulation or inherited genetic defects in metabolism. In addition, excess alcohol, if consumed while fasting, can cause hypoglycemia, as can several medications (Berber 2013).

Proactively taking steps to maintain glucose levels within a healthy range is an important long-term strategy. For diabetics, this includes ensuring medications are dosed appropriately and combined with careful monitoring of glucose levels. Among people who experience reactive hypoglycemia, effective prevention hinges upon avoidance of post-meal surges in glucose concentrations through diet modulation and a variety of natural interventions. For example, the rate of carbohydrate absorption can be slowed by inhibiting the alpha-glucosidase and alpha-amylase enzymes via supplementation with green coffee extract and Irvingia gabonensis (Ishikawa 2007; Oben 2008). Moreover, the prescription anti-diabetic drug acarbose also inhibits the alpha-glucosidase enzyme and slows the absorption of glucose. Unfortunately, many physicians overlook the potential of this well-studied drug to stabilize post-meal glucose levels and mitigate the exaggerated insulin spike that leads to hypoglycemia (Bavenholm 2006; Hanefeld 2007; Ozgen 1998).

In this protocol you will learn about the physiology of glucose control and how the body orchestrates a complex system of checks and balances to keep blood sugar levels in a healthy range. You will also learn about some of the ways these regulatory mechanisms can fail and lead to hypoglycemia and what kind of symptoms this can cause. Hypoglycemia management strategies will be outlined along with integrative approaches and dietary considerations to help stabilize glucose levels and avert episodes of low blood sugar.

Maintaining glucose balance is critical. When blood sugar is too high for too long (chronic hyperglycemia), irreversible damage can be done to various tissues. On the other hand, severe hypoglycemia may cause a person to become comatose or even die. To prevent these complications, the body has adopted a variety of mechanisms to maintain plasma glucose levels within certain values, a process known as homeostasis, which is controlled by a symphony of interrelated checks and balances within the body, including neurotransmitters, hormones, and organ systems (Klement 2012).

Blood glucose is mainly derived from two sources: diet and synthesis in the liver via a process known as hepatic blood sugar production (Boden 2004). Excess dietary glucose can be stored in the liver as glycogen. Glucose can be released from glycogen in a process known as glycogenolysis. Another critical mechanism for glucose production in the liver is when glucose is newly synthesized from precursors; this process is known as hepatic gluconeogenesis (Cersosimo 2011). During gluconeogenesis, the liver converts certain amino acids or metabolites, such as alanine, glycerol, and lactate into glucose (Watford 2006).

Hormonal Regulation

Islets are specialized clusters of hormone-secreting cells in the pancreas. Within the islets are alpha cells that secrete glucagon and beta cells that secrete insulin. The major effect of glucagon is to stimulate glycogenolysis and gluconeogenesis in the liver, which results in an increase in the blood levels of glucose (Lee 2012). During carbohydrate ingestion, insulin inhibits glucagon and stimulates glucose uptake primarily in skeletal muscle, effectively lowering the blood glucose concentration (Lee 2011; Roth 2007).

Glucagon, as well as growth hormone, cortisol, and epinephrine all oppose the action of insulin and are known as “counter-regulatory hormones” (Lager 1991).

In the absence of dietary carbohydrate, (eg, during starvation) hepatic glucose production by gluconeogenesis and glycogenolysis guards against hypoglycemia (Rothman 1991; Cahill 2006). Upon carbohydrate ingestion, hepatic glucose production is reduced and blood glucose levels are maintained by dietary glucose absorbed through the gastrointestinal tract.

Dietary Contribution to Glucose Levels

The contribution of diet to glucose levels is relatively straightforward: dietary carbohydrates are broken down into glucose and absorbed through the gastrointestinal tract after ingestion. Thus, eating a meal containing large amounts of carbohydrate contributes to a rapid elevation of blood glucose levels. Ingestion of a pure glucose solution causes detectable elevations in blood glucose levels in as little as 15 minutes (Shrayyef 2010). On the other hand, the more complex or “fibrous” the carbohydrates ingested are, the slower the subsequent glucose elevations. Moreover, the addition of fats and proteins to a meal can also slow glucose absorption (Gemen 2011; Bajorek 2010; Riccardi 1991). This is why a high-fiber diet with moderate amounts of slowly-digested carbohydrate, good quality protein, and healthy fats (eg omega-3 fatty acids from fish) is recommended for people with impaired glucose control, such as those with type 2 diabetes.

With regard to hypoglycemia, the contribution of diet is somewhat counterintuitive. If too much rapidly-digested carbohydrate is consumed and absorbed quickly, an ensuing hypoglycemic episode can follow if the body generates an exaggerated insulin response to bring post-meal glucose levels back down (Kuipers 1999). This is called reactive hypoglycemia (Bell 1985). Thus, interventions aimed at reducing the rapid absorption of dietary carbohydrate can help avoid the reactive drop in blood sugar following an overly exaggerated insulin spike.

Regulation of Glucose Levels Following a Meal

Once glucose is absorbed from the gastrointestinal tract into the bloodstream, the body must keep blood sugar from rising to levels above normal since too much glucose in the blood can damage tissues and contribute to inflammation and vascular stress (Averill 2009). The process of controlling after-meal glucose levels is a complex interplay of several organs, hormones, and neurotransmitters (Shrayyef 2010).

When glucose levels rise following a meal, the pancreas releases the hormone insulin. Insulin triggers numerous tissues throughout the body to initiate the breakdown and/or storage of glucose, thus bringing blood glucose levels back down. Insulin stimulates the uptake of glucose from the blood into muscle and fat tissue, where it can either be stored or broken down and used to meet cellular energy demands. Insulin also suppresses the release of glucose from the liver, a significant source of glucose between meals (Shrayyef 2010).

Causes of hypoglycemia can broadly be classified as reactive or fasting, insulin-mediated or non-insulin-mediated, and drug-induced or non drug-induced (Merck 2012).

Drug-Induced Hypoglycemia

Iatrogenic (treatment-related) hypoglycemia. Hypoglycemia is most commonly associated with the treatment of diabetes, either with insulin or oral drugs that reduce blood sugar levels (Merck 2006; Cryer 2009). This is known as “iatrogenic hypoglycemia,” meaning it occurs as an adverse effect of treatment. In addition to glucose-lowering drugs, other drugs such as pentamidine (Nebupent®) or quinine may cause hypoglycemia (Merck 2006).

Insulin injections, which are the staple treatment for type 1 diabetes and are also used in type 2 diabetes, contribute to hypoglycemia directly by causing glucose disposal into peripheral tissues such as fat and skeletal muscle.

Several reviews of published studies reveal that attempts to aggressively lower blood glucose levels with intensive insulin therapy are associated with a 2-2.5-fold higher risk of severe hypoglycemia (Bloomfield 2012). One study found that the incidence of severe hypoglycemia was 3-fold higher among type 2 diabetic patients receiving insulin compared to those not receiving insulin (Samann 2012). The severity of this is evidenced by the ACCORD trial, wherein type 2 diabetics assigned to the intensive glucose-lowering treatment group experienced significantly more hypoglycemia and an increase in all-cause mortality (Gerstein 2008). In fact, for the group receiving the intensive treatment approach, the clinical trial was stopped after a 3.4-year follow-up period because the investigators noted a 22% higher all-cause mortality (Riddle 2010).

Another type of drug often used to treat type 2 diabetes, sulfonylureas, are well-known causes of hypoglycemia (Holstein 2010). These drugs work by increasing pancreatic insulin secretion without regards to glucose level. Although the risk of hypoglycemia associated with sulfonylurea drugs is well known, studies suggest that this risk may be underappreciated, especially in patients who are older or have reduced kidney function (Holstein 2010). Metformin, an anti-diabetic drug that works by suppressing gluconeogenesis, is effective at controlling glucose levels in type 2 diabetic patients and has been shown to be far less likely to cause hypoglycemia. In fact, one study involving more than 50 000 subjects showed that the risk for developing hypoglycemia was 179% greater among diabetics receiving sulfonylureas compared to those taking metformin (Bodmer 2008).

Antibiotics. Certain antibiotics are known to cause hypoglycemia. For example, the fluoroquinolone levofloxacin (Levaquin®) enhances insulin secretion by a mechanism similar to sulfonylureas and induces hypoglycemia, which sometimes may be life-threatening (Kelesidis 2009). Hypoglycemia has also been observed after the administration of norfloxacin (Noroxin®), another fluoroquinolone drug (Mishra 2012).

Non Drug-Induced Hypoglycemia

Reactive hypoglycemia. Reactive hypoglycemia occurs after eating, usually 2-5 hours after food intake, and is caused by insulin hypersecretion (McCool 1977; Hofeldt 1989; Altuntas 2005; Meier 2006; Bell 1985). This form of hypoglycemia is also more prevalent in people who have undergone Roux-en-Y gastric bypass surgery; it was reported to occur as a late complication in about 72% of the patients who underwent gastric bypass surgery (Meier 2006; Mingrone 2012). This is thought to occur, at least in part, as a result of nesidioblastosis, excessive function of the cells of the pancreas that produce insulin (Rabiee 2011).

Reactive hypoglycemia may also occur in people who have not had gastric bypass surgery (Mayo Clinic 2012a). In some cases, individuals have symptoms similar to reactive hypoglycemia without the corresponding low blood sugar levels. Nevertheless, these patients often reduce their risk of this condition by avoiding rapidly-absorbed carbohydrates and eating a high-fiber diet with moderate amounts of quality protein and fat (eg, omega-3 fatty acids) (Gaby 2011; Bell 1985). Reactive hypoglycemia is more common in overweight and obese individuals, people that are insulin-resistant as well as those with a family history of type 2 diabetes (Hamdy 2013).

Glucagon deficiency. Glucagon deficiency can cause hypoglycemia, and together with other hormones such as epinephrine, glucagon represents a primary defense against hypoglycemia (Hussain 2005).

One of the challenges in treating iatrogenic hypoglycemia is that in some diabetic patients with more pronounced damage to the pancreas, their glucagon response to hypoglycemia is defective, which can make their hypoglycemic episodes more severe and prolonged (Cryer 1983; Cryer 2009; Taborsky 2012).

Addison’s disease. Cortisol is an anti-inflammatory hormone produced by the adrenal glands that also helps sustain glucose levels. Addison’s disease is a condition of adrenal insufficiency wherein the production of cortisol is impaired (MedlinePlus 2011). Addison’s patients often develop hypoglycemia, among other symptoms (Meyer 2012).

Fasting-induced hypoglycemia. Fasting-induced hypoglycemia is usually associated with either an insulin-secreting tumor, known as insulinoma, or with genetic mutations. Alternatively, excess alcohol consumption after a period of fasting could also trigger a bout of hypoglycemia. This is because alcohol cannot be excreted from the body as is, but it first needs to be metabolized in the liver (Berg 2002). Alcohol metabolism prevents the production of pyruvate, which is an important building block of gluconeogenesis (Berg 2002; Devenyi 1982; Watford 2006). Alcohol alone does not necessarily cause hypoglycemia, but it does when combined with the additional insult of fasting-induced depletion of liver glycogen reserves. Something similar is seen when fasting and alcohol ingestion are combined with sulfonylureas, drugs which enhance the secretion of insulin. In elderly individuals with type 2 diabetes, even a small amount of alcohol during a short-term fast were shown to lower blood glucose levels. In this case, the effect is compounded by sulfonylureas (Burge 1999).

Polycystic ovary syndrome (PCOS). PCOS is associated with obesity and an exaggerated insulin response, and reactive hypoglycemia is significantly more prevalent in PCOS sufferers than the general population (Kasim-Karakas 2007).

Congenital/genetic causes. Fasting-induced hypoglycemia is associated with a number of congenital disorders, many of which are diagnosed in childhood and persist in adulthood. Some examples of conditions in this group are glycogen storage or fatty acid metabolism diseases and gluconeogenesis disorders (Douillard 2012).

Exercise-induced hypoglycemia. Exercise-induced hypoglycemia may be caused by pyruvate-related mutations that result in a massive insulin hypersecretion in response to anaerobic exercise (Meissner 2005). It causes hypoglycemia specifically during anaerobic exercise because pyruvate in the blood is increased by the high intensity activity. Another cause of exercise-induced hypoglycemia is hypoglycemia-associated autonomic failure (HAAF), which may be mediated by an exaggerated endorphin response to exercise.

Other Causes

Additional causes of hypoglycemia include (Toth 2013):

• Advanced liver or kidney disease
• Autoimmune disease
• Sepsis
• Hypopituitarism

Symptoms of hypoglycemia can be organized into 2 primary categories: neurogenic and neuroglycopenic. Neurogenic symptoms are the result of activation of the sympathetic nervous system when glucose levels drop too low. These include shaking or tremors, a pounding heart, nervousness or anxiety, sweating, and tingling. Neuroglycopenic symptoms arise when insufficient glucose is available to fuel the brain. These include warmth, confusion, and drowsiness. During prolonged, severe hypoglycemia dramatic brain dysfunction can occur, potentially leading to coma and death (Towler 1993; MedlinePlus 2012).

Hypoglycemic symptoms including anxiety, sweating, tremors, and fatigue do not always correlate with glucose levels (Nippoldt 2013). Individuals with low glucose levels may be asymptomatic or unaware of their hypoglycemia, and others with normal glucose levels may display hypoglycemic symptoms (Bakatselos 2011; Alken 2008; Palardy 1989). 

Diagnosis

A set of diagnostic criteria called Whipple’s Triad are used to establish a diagnosis of hypoglycemia. Whipple’s Triad includes 1) clinical symptoms/signs consistent with hypoglycemia; 2) low blood glucose levels at the time of the symptoms; and 3) relief of symptoms after the administration of glucose (Ng 2010; Bjelakovic 2011; Cryer 2009; Mayo Clinic 2012b).

If onset is associated with a drug known to lower blood glucose, such as insulin, then the cause is deemed to be iatrogenic (treatment related) (Cryer 1992; Martorella 2011). If the underlying cause of hypoglycemia is not immediately obvious, several tests can be conducted to help determine the cause. Laboratory tests that may be helpful include: fasting glucose and insulin, an oral glucose tolerance test (which measures the body’s ability to react to ingestion of sugar), C-peptide levels (which may be elevated with use of sulfonylureas), cortisol (which can measure adrenal insufficiency), magnetic resonance imaging (MRI) (which can help identify an insulin-secreting tumor), and other blood tests (Cryer 2009; MedlinePlus 2013; Toth 2013; Hamdy 2013).

Conventional Treatment

Management of hypoglycemia includes two priorities: 1) immediately restoring glucose levels in a patient who presents with severe hypoglycemia, and 2) taking steps to help stabilize long-term glucose control and prevent additional episodes of hypoglycemia.

Immediate treatment of hypoglycemia involves the administration of glucose (Merck 2007). Another option, in some cases, is to administer glucagon. However, this is ineffective in people who have been fasting or have experienced prolonged hypoglycemia. This is because glucagon stimulates glycogenolysis to restore blood glucose levels, but in fasting or prolonged hypoglycemic patients, liver glycogen stores have already been used up (Merck 2007; Roach 2012; Dohm 1986; Butler 1989; Koubi 1991; Kimmig 1983; Castle 2010).

From a long-term management perspective, prevention of hypoglycemia encompasses treatment of the underlying cause. Since hypoglycemia most often occurs in diabetics being treated with glucose-lowering therapy, modification of dose or switching to a different drug is typically considered. For example, use of sulfonylureas for glucose management in type 2 diabetics is associated with increased frequency of hypoglycemia compared to metformin (Bodmer 2008).

Implantable Continuous Glucose Monitoring Devices

Many type 1 diabetics who use insulin have made the transition from self-injections and adjustable glucose infusion pumps to continuous glucose monitoring systems, also known as “closed-loops,” in which an implantable device measures blood glucose and constantly adjusts the insulin infusion rate. These systems allow for continual monitoring and adjustment of the insulin infusion rate without the need for patient predictions (Hovorka 2011).

In one study, type 1 diabetics on implantable insulin pumps were randomly assigned in crossover fashion to their standard therapy or a closed-loop system. The closed-loop system achieved better overnight control of insulin and reduced the risk of hypoglycemia (Hovorka 2011).

The use of integrated closed-loop control has been shown to reduce hypoglycemic episodes 2.7-fold over traditional insulin therapy. Moreover, it provided a 6-fold reduction in overnight hypoglycemia. This represents an important step toward improving patient safety and decreasing the risk of complications (Breton 2012). In another study, a closed-loop delivery system combining glucose monitoring with insulin and glucagon infusions dramatically reduced the number of participants who developed at least one hypoglycemic episode from 53% to 7% (Haidar 2013).

Improving Hypoglycemia Awareness

A major problem in the treatment of type 1 diabetes is patient unawareness of hypoglycemia. This occurs due to defects in the neural response that normally accompanies low blood glucose levels. The result is that individuals with type 1 diabetes may not be aware their glucose levels are falling too low (Cryer 2008). This phenomenon is called hypoglycemia-associated autonomic failure (Vele 2011).

Some evidence suggests that naltrexone (Revia®), a drug used in the management of addictive disorders, may help improve hypoglycemia awareness (Feeney 2001; Blasio 2013). It works by blocking opioid receptor signaling. Studies show that blocking opioid receptor signaling helps improve the perceptibility of hypoglycemia (Vele 2011). As of the time of this writing, naltrexone, at a 25-50 mg/day dose, is being tested in type 1 diabetics to determine whether it can prevent hypoglycemia unawareness (Kumar 2012).

Fluoxetine (Prozac®), the selective serotonin reuptake inhibitor used as an antidepressant, may also be useful for increasing hypoglycemia awareness. In one study, 20 healthy patients were subjected to an experimentally controlled bout of hypoglycemia, treated with 40-80 mg/day fluoxetine for 6 weeks, and then re-tested. The study found that this treatment increased several categories of counter-regulatory responses to hypoglycemia and resulted in an increase in endogenous glucose production (Briscoe 2008). The increased counter-regulatory response may allow patients to be more aware of an impending hypoglycemic episode.

The Overlooked Potential of Acarbose in the Management of Reactive Hypoglycemia Individuals who suffer from reactive hypoglycemia may not realize that glucose levels going too high after a meal may be the culprit driving their symptoms. This seemingly counterintuitive phenomenon is the result of ingesting large amounts of carbohydrate, which are then quickly broken down to glucose by enzymes in the gastrointestinal tract before being absorbed. The subsequent spike in blood glucose levels triggers an exaggerated release of insulin from the pancreas, which then causes glucose levels to plummet to a hypoglycemic state (Brun 2000). One way of avoiding post-meal hypoglycemia is reducing carbohydrate consumption. However, this can be difficult in modern society where so many starchy foods are readily available. Fortunately, there is another method that most people who suffer from hypoglycemia are probably unaware of, and which is overlooked by many physicians: the anti-diabetic drug acarbose (Bavenholm 2006; Hanefeld 2007; Gerard 1984; Hasegawa 1998; Ozgen 1998; Derosa 2012). One of the key enzymes that break down carbohydrate into glucose is alpha-glucosidase. Acarbose inhibits alpha-glucosidase, thereby slowing the rate of glucose absorption into the bloodstream. This drug is typically used to help type 2 diabetics keep their blood sugar from going too high, but it may also benefit those who suffer from reactive hypoglycemia by suppressing the post-meal glucose surge that triggers excess insulin release and subsequent hypoglycemia (Bavenholm 2006; Hanefeld 2007; Derosa 2012). Several studies have investigated the efficacy of acarbose in managing reactive hypoglycemia. In one study, 21 subjects with reactive hypoglycemia were treated for 3 months with acarbose. Before the treatment, the subjects’ lowest glucose level 3 hours after an oral glucose challenge was 39 mg/dL. After 3 months of treatment with acarbose, the lowest glucose level 3 hours after the glucose load was 67 mg/dL. Moreover, the subjects’ insulin levels were reduced within the first few hours following a meal after treatment with acarbose. The researchers concluded “These results confirm that acarbose may be of value in preventing reactive hypoglycemia by reducing the early hyperglycemic stimulus to insulin secretion…” (Ozgen 1998). Another study demonstrated the immediate benefit of acarbose. Twenty-four subjects with postprandial hypoglycemia symptoms were given an oral sucrose challenge. Along with the sucrose solution, participants were given either 100 mg acarbose or a placebo. Compared to subjects who received placebo, those who took acarbose experienced significantly less reactive hypoglycemia after the sucrose challenge. Also, in some of the subjects who took acarbose, the post-challenge glucose level variance was attenuated: both the highest and lowest glucose levels were closer to baseline than in those who took the placebo. This indicates that acarbose blunted the post-challenge spike in glucose levels and the subsequent drop that characterizes reactive hypoglycemia. Insulin levels were also reduced in subjects who took acarbose (Gerard 1984). Additional evidence comes from a small study in which subjects with type 2 diabetes and symptoms of reactive hypoglycemia were treated with acarbose for one month. In this study, each subject took either 50 or 100 mg of acarbose 3 times daily before meals. Before treatment, all the subjects in the study experienced symptoms such as weakness, palpitation, and dizziness after meals. After one month of treatment with acarbose, these symptoms subsided and subjects’ post-meal glucose and insulin levels stabilized (Hasegawa 1998).

For those who want to avoid prescription drugs, there are nutrients described later in this chapter that suppress alpha-glucosidase and other functions in the digestive tract that can cause too much glucose to be rapidly absorbed.

Life Extension® suggests that most healthy people strive to maintain fasting glucose levels between 80 and 86 mg/dL and 2-hour post-meal glucose levels no more than 40 mg/dL above fasting levels, or a maximum of 125 mg/dL. Adjustment of dietary habits can help stabilize glucose levels and achieve these goals for many people. In addition to the strategies outlined in this protocol, readers are encouraged to review the protocol on Diabetes.

One dietary strategy for avoiding a rapid spike in blood sugar levels after a meal is increasing intake of dietary fiber, which slows the rate of carbohydrate absorption. For example, a study on 63 patients with type 1 diabetes assessed the effect of 24 weeks of a high- or low-fiber diet. Compared to 15 g of fiber daily, those who ate 39.1 g on average exhibited half as many episodes of hypoglycemia (Giaco 2000). The increased fiber intake in this study was accomplished by eating more fruits and vegetables.

A more direct way to reduce the glycemic impact of the diet is to consume fewer carbohydrates. This was tested in a group of subjects with severe reactive hypoglycemia who had recently undergone Roux-en-Y gastric bypass surgery for weight loss (Kellogg 2008). In this study, the high-carbohydrate meal contained 79% carbohydrates, 11% fat, and 10% protein, and the low-carbohydrate meal contained 2% carbohydrates, 74% fat, and 24% protein. Of 12 participants, 10 (83%) showed improvement in their symptoms, and of these, 3 (25%) had complete resolution of their symptoms (Kellogg 2008). These findings suggest that a low-carbohydrate diet attenuates pathological glycemic excursions in this population (Cui 2011).

Typical dietary suggestions for reactive hypoglycemia include (Gaby 2011; Hamdy 2013; Nippoldt 2013):

• Avoid refined carbohydrates (eg, white rice, white flour).
• Eat several small meals and snacks throughout the day (6 small meals or in-between meal snacks).
• Avoid excess alcohol while fasting (or at least consume food while drinking alcohol).
• Eat foods with a lower glycemic index. These are foods that raise blood sugar levels more slowly (eg, lean protein, high-fiber foods).

Stabilization of glucose levels following a meal may help avert reactive hypoglycemia. Several natural interventions may help reduce post-meal glycemic variability.

Fiber

Supplementation of the diet with fiber such as fructooligosaccharides (FOS) may help stabilize post-meal glucose levels by prolonging carbohydrate absorption (Wursch 1997; Sabater-Molina 2009; Gietl 2012). This may be beneficial for people prone to reactive hypoglycemia.

Fructooligosaccharides (FOS) are fermentable prebiotic fibers found in plant foods such as onion, garlic, chicory, asparagus, artichokes, and bananas (Sabater-Molina 2009; Gietl 2012). A study found that supplementation with 20 g of FOS daily for two weeks in people with reactive hypoglycemia resulted in significantly improved blood glucose profiles and fewer episodes of hypoglycemia (Sorensen 2010).

Chromium

Chromium is an essential trace mineral that plays a significant role in sugar metabolism. Chromium supplementation helps control blood sugar levels in type 2 diabetes and improves metabolism of carbohydrates (Ghosh 2002; Jovanovic 1999). A small, double-blind, crossover trial assessed the effects of chromium on 8 women with symptoms of reactive hypoglycemia. Supplemental chromium, at a daily dose of 200 mcg for 3 months, led to improvements in both blood sugar metabolism parameters and hypoglycemic symptoms such as sweating, trembling, and blurred vision (Anderson 1987). 

Green Coffee Bean Extract

Green coffee bean extract, an antioxidant-rich mixture from unroasted coffee beans, may temper post-meal spikes in glucose (Nagendran 2011). Chlorogenic acid, a compound derived from green coffee extract, has been shown to reduce glucose absorption in healthy volunteers (Thom 2007). One compelling study showed that people not taking green coffee extract had glucose levels of 130 mg/dL one hour after sugar ingestion. In this same study, glucose levels of subjects taking 400 mg of green coffee extract dropped to 93 mg/dL after sugar ingestion (Nagendran 2011).

Chlorogenic acid may reduce postprandial hyperglycemia both by shutting down excess liver glucose production and also stimulating glucose uptake into skeletal muscle (Ong 2012; Ong 2013). Another means by which chlorogenic acid acts to suppress post-meal glucose surges is by inhibiting alpha-glucosidase. This intestinal enzyme breaks apart complex sugars and enhances their absorption into the blood (Pusztai 1998). Slowing the absorption of common sugars (including sucrose) limits after-meal glucose spikes (Alonso-Castro 2008).

White Bean Extract (Phaseolus vulgaris) and Irvingia Gabonensis

White bean extract (Phaseolus vulgaris) and Irvingia gabonensis are powerful blockers of the enzyme alpha-amylase, which is secreted by the pancreas (Mosca 2008; Obiro 2008). Alpha-amylase breaks down long-chain, complex starch molecules into simple sugars and short-chain oligosaccharides for absorption in the small intestine. Blocking alpha-amylase inhibits the metabolism of starches and slows the rate at which free sugars are absorbed (Udani 2004; Celleno 2007; Oben 2008; Ngondi 2009).

In one double-blind, placebo-controlled study of obese but otherwise healthy adults, one month of supplementation with Irvingia gabonensis produced a 5.3% body weight loss in supplemented patients compared with only a 1.3% loss in the control group (Ngondi 2005). These individuals also saw significant improvement in their lipid profiles. Additional studies confirm these findings, demonstrating significant reductions in body fat  waist circumference, blood sugar levels, and markers of fat tissue regulation (Oben 2008; Ngondi 2009).

White bean extract shows enormous potential for preventing the blood sugar and insulin spikes associated with many chronic health disorders (Preuss 2007). Slowing starch digestion prolongs the amount of time it takes for the stomach to empty its contents, reducing the amount of carbohydrate calories released at any one time into the intestine (Layer 1986).

White bean extracts operate along numerous overlapping pathways in multiple, related physiological systems. Laboratory research shows that supplementation with white bean extract promotes weight loss in obese animals, with dramatic reduction in fat accumulation without loss of muscle mass (Santoro 1997; Pusztai 1998). Plasma insulin levels also dropped substantially following a high-carbohydrate meal including white bean extract in pre-clinical studies, reflecting a much more gradual rise in blood sugar levels (Pusztai 1998).

Seaweed Extracts

Extracts from kelp (Ascophyllum nodosum) and bladderwrack (Fucus vesiculosus) have been demonstrated to inhibit the activity of the digestive enzymes alpha-amylase and alpha-glucosidase (Paradis 2011). Inhibition of these enzymes interferes with the digestion of dietary starches and may reduce or slow the absorption of high glycemic carbohydrates (Preuss 2009).

L-arabinose 

Sucrose (table sugar) is composed of 2 simple sugar molecules, glucose and fructose. It is poorly absorbed in the intestine in this form. In order to be utilized, it must first be broken down by the digestive enzyme sucrase. Blocking the enzymatic action of sucrase therefore reduces uptake of sucrose. Researchers have identified a potent sucrase inhibitor called L-arabinose. L-arabinose, an indigestible plant compound, cannot be absorbed into the blood. Instead, it remains in the digestive tract and is eventually excreted (Seri 1996; Osaki 2001). By blocking the metabolism of sucrose, L-arabinose inhibits the spike in blood sugar and fat synthesis that would otherwise follow a sugar-rich meal (Osaki 2001).