Continuing Education Activity

Low carbohydrate (low-carb) diets are a strategy for weight loss. Today, there continues to be an interest in low-carb approaches. While all low carbohydrate approaches reduce the overall intake of carbohydrates, there is no clear consensus on what defines a low-carb diet. Studies have defined low carbohydrate as a percent of daily macronutrient intake or total daily carbohydrate load. This activity will review the evidence and effectiveness of low-carb approaches in clinical medicine for an interprofessional team to consult with patients who might benefit from such a dietary strategy.

Objectives:

• Outline low carbohydrate diets in terms of percent of macronutrient content and total carbohydrate load.
• Review the evidence behind low carbohydrate diets.
• Describe the potential concerns surrounding low carbohydrate diets.
• Explain the importance of collaboration and communication among the interprofessional team to ensure the appropriate selection of candidates for low carbohydrate diets and educate patients to provide the best possible outcome.

Introduction

Since 1860, and more recently, in 1972, low carbohydrate (low-carb) diets have been a strategy for weight loss. Today, there continues to be an interest in low-carb approaches. While all low carbohydrate approaches reduce the overall intake of carbohydrates, there is no clear consensus on what defines a low-carb diet. There are three macronutrients—carbohydrates (4 kcal/gm), fat (9 kcal/gm), and protein (4 kcal/gm) found in food. Therefore, studies have defined low carbohydrate as a percent of daily macronutrient intake or total daily carbohydrate load. This article will define it as:

1. Very low-carbohydrate (less than 10% carbohydrates) or 20 to 50 gm/day
2. Low-carbohydrate (less than 26% carbohydrates) or less than 130 gm/day
3. Moderate-carbohydrate (26% to 44%)
4. High-carbohydrate (45% or greater)

For reference, the institute of medicine proposes Americans obtain 45% to 65% of calories from carbohydrates.[1] This article will review the evidence and effectiveness of low-carb approaches in clinical medicine.

Function

Low-carb approaches stem primarily from the hypothesis that lowering insulin, a critical hormone that produces an anabolic, fat-storing state, improves cardiometabolic function and induces weight loss.[2] This approach has been recently called the carbohydrate-insulin model.[3] Studies have shown low-carb approaches to be superior to other dietary methods in producing rapid weight loss for the first 6 to 12 months.[4][5][6] While diets inducing weight loss produce a caloric deficit, the mechanism of low-carb diets remains in debate. When lowering carbohydrates from the diet, the macronutrient intake of fat and protein generally increases to compensate for the reduction of carbohydrates.

One hypothesis of why low-carb approaches produce rapid weight loss compared to other diets is that fats and protein increase satiety and produce less concomitant hypoglycemia. This increase in satiety and less rebound hypoglycemia reduces hunger and overall food intake and produces a caloric deficit. Another hypothesis contends that low-carb diets can produce a higher metabolic burn than high-carb diets. In recent studies, there appears to be a metabolic advantage of approximately 200 to 300 more calories burned compared to an iso-caloric high-carb diet.[2][7] However, these theories remain controversial.[8]

The ketogenic (keto) diet, a specific low-carb version, deserves mention. Keto diets restrict carbohydrates to induce nutritional ketosis and typically limit carbs to 20 to 50 grams daily. Restricting carbs to under 50 gms induces glycogen depletion and ketone production from the mobilization of fat stored in adipose tissue. Nutritional ketosis produces ketone bodies (acetoacetate, acetone, and beta-hydroxybutyrate) and is measurable as serum or urinary ketones. Nutritional ketosis generally increases serum ketones from 1 mmol/L to 7 mmol/L but does not produce metabolic acidosis. Diabetic ketoacidosis, by definition, includes metabolic acidosis, hyperglycemia, and serum ketones (generally over 20 mmol/L).[9]

The term net carbs refer to the total amount of fully digestible carbohydrates contained in a meal. This can be calculated carbs by subtracting the whole amount of fiber and half the amount of sugar alcohols from the amount of total carbs. The only nutritional impact of using net carbs is it may help the patient to choose foods that are higher in fiber.

Despite the debate, it is clear from numerous systematic reviews that low-carb diets are as effective, if not more effective, for weight loss compared to other diets. The evidence for benefits and concerns for low-carb will be further delineated below.

Issues of Concern

Several theoretical concerns about the long-term safety of low-carb diets deserve mention. Low-carb diet safety concerns relate to ketosis, long-term cardiovascular safety, lipid, and renal effects.

Ketosis

Nutritional ketosis can be induced in the keto diet, the induction phase, and when carb load is limited to less than 10% of macronutrient intake or 20 to 50 gm/day of carbohydrates. However, there is no evidence that very low-carb intake produces metabolic ketoacidosis and remains safe in patients, even with type 2 diabetes.[9][10] While there have been cases of diabetic ketoacidosis (DKA) with concomitant SGLT2 inhibitors in patients with type 2 diabetes, it is unclear if the very low carb approach increases the risk of DKA with SGLT2 use. The recommendation is for caution with the use of ketogenic diets with the concomitant use of SGLT-2 inhibitors.[11]

Mortality and Cardiovascular Safety

There have been several studies linking low-carb diets to increased mortality. Epidemiological studies and meta-analyses have shown an increased mortality risk with a carbohydrate intake of less than 40%.[12][13] However, the recent Prospective Urban Rural Epidemiology (PURE) study, a large prospective nutrition study involving over 135,000 participants across the globe, found a relationship between increased mortality and higher carbohydrate intake and lower mortality associated with higher fat intake.[14] Another prospective cohort study found that a healthy low-carb diet and low-fat diets were associated with lower mortality, and unhealthy low-carb and low-fat diets were associated with higher mortality.[15] This suggests that the quality of the food matters, not just the macronutrient itself. The ongoing effect is unclear until long-term, randomized studies can be undertaken.

Lipid Response

Incorporating more fat and protein in response to reducing dietary carbs has led to concerns about the effect of low-carb dieting on lipids, specifically LDL cholesterol. Recent systematic reviews of low-carb diets on lipids demonstrate a neutral to a small increase in LDL but a favorable triglycerides reduction and an increase in HDL cholesterol, particularly those assigned to the very low-carb intervention.[16][17] Research recently indicated that a subset of lean individuals might have a hyper LDL response with ketogenic diets, a term called lean mass hyper-responders.[18] Due to the varied and individualized response, recommendations are for baseline fasting lipid profile, periodic testing, and shared decision making.

Renal Function

With a potentially higher protein intake on low-carb diets, some have expressed concerns about renal function. However, depending on specific goals, athletes should ingest protein loads to optimize muscle protein synthesis (1.6 gm/kg) or endurance sports (0.8 gm/kg).[19][20] Encouraging higher protein loads to support physical activity can also help with improving body composition and metabolic adaptations. In general, there are no data to associate high protein load with worsening kidney function in those with normal kidneys.[21] For those with chronic kidney disease, a low or very-low-protein diet (0.2-0.8 gm/kg/day) may be recommended to prevent further renal deterioration.[22]

Clinical Significance

The study of low-carb diets has centered on weight loss in obese and overweight people and patients with or at risk for cardiometabolic diseases such as type 2 diabetes and nonalcoholic fatty liver disease. Ketogenic diets have also been used for seizure disorders and, more recently, have found use in the athletic population as an alternative fuel for performance and health.

Weight Loss

Most research on low-carb approaches has shown that a low-carb diet, specifically ketogenic approaches, induces rapid induction of weight loss. Initial weight loss is due partly to water loss, but fat loss occurs with adherence to the low carb approach. With all dietary interventions, as adherence to the diet wanes, the weight loss effect becomes similar to other dietary approaches after one year.[23] Notably, most low-carb diet studies generally use an ad-libitum approach to caloric intake (limiting carbs instead), while most comparison diets are calorie-restricted. In general, shared decision-making is a valid and person-centered approach to determining nutritional strategies for weight loss.

Type 2 Diabetes

Before medications, carbohydrate control has been the cornerstone of glycemic control in both type 1 and type 2 diabetes. Dietary carbohydrates increase insulin needs, and reduction of carbohydrate intake can improve glycemic control.[24] A recent study demonstrated a significant reduction of insulin and oral medications and hemoglobin A1c reduction with ketogenic approaches while demonstrating a high adherence to the intervention at 12 months.[25][26] Also, markers of cardiometabolic risk factors improved.[27] A systematic review and meta-analysis found low-quality evidence that low-carb approaches increase type 2 diabetes remission and are generally safe.[28]  

Approaches to nutritional lifestyle and approaches to diabetes (medical nutrition therapy) have included low carb as an option in recent guidelines.[29][30][30] Recent prospective and randomized controlled trials have consistently benefited glycemic control, weight loss, and sustained medication reduction using a very low carb approach (less than 14% of energy from carbohydrates).[31][32][33]

Cardiovascular Risk Factors

As mentioned above, the effect of low-carb diets on cardiovascular risk factors continues to be controversial. While a few studies have demonstrated an increase in LDL cholesterol with low-carb diets, others showed negligible changes. However, other metabolic markers, such as lowering triglycerides, and increases in HDL, have been demonstrated with low-carb diets.[4][27][17]

Other Issues

Ketogenic diets have been used successfully since 1920, before the existence of medications for epilepsy.[9][34] Recent studies have shown that acne, cancer, non-alcoholic fatty liver disease, polycystic ovary syndrome, and Alzheimer disease may improve with ketogenic diets.[9][35] Recently use of keto diets to provide sustained, and steady fuel for endurance sports in athletic individuals and the optimization of body composition in high-intensity training for the recreational population have also undergone testing.[36][37]

Enhancing Healthcare Team Outcomes

Initiation of a Low-Carb Lifestyle

After a shared decision-making process with the patient, there are numerous ways to start a patient on a low-carb diet. Low-carb nutrition may be advisable for those who desire healthy or athletic performance, weight loss, improvement of glycemic control for type 1 or 2 diabetes, or a seizure disorder.

• First, understanding what macronutrients are and their relation to food is a critical part of counseling.
• Secondly, determine the patient's desire for either small steps or a rapid induction phase through motivational interviewing and S.M.A.R.T goal setting.
• Limitation of added sugar (sucrose) and refined carbohydrates is critical in the overall improvement of food quality and will generally reach a moderate carbohydrate (less than 45% carbohydrates) level.
• A way to initiate low-carb is through a rapid induction phase of 2 to 4 weeks, with 20 to 50 gms of carbohydrates to induce nutritional ketosis. Ad libitum vegetables that grow above the ground and are lower in carbohydrate content are encouraged. Additionally, carbs should be limited to those found in whole, unprocessed food.
• Finally, after the induction phase, depending on goals, patients can remain in the keto phase or slowly add healthy carbohydrates from whole, unprocessed vegetables and low-glycemic, high fiber fruit (i.e., berries).

Maintenance of a Low-Carb Lifestyle

If limited initially or during the induction phase, full-fat dairy, legumes, and whole grains can also be added during this maintenance phase as long as goals are maintained and tolerated without any hypersensitivity or an adverse response. The lifelong maintenance phase can then continue in accordance with patient preference. Periodic monitoring of cardiovascular risk markers and control of cardiometabolic disease should also be a priority. Those with type 2 diabetes require close monitoring for hypoglycemia, and reduction of insulin or hypoglycemic medications is prudent with rapid reductions in fasting glucose.[38]  [Level 4]