Low Carbohydrate Diet

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Robert Oh

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Sandeep Sekhon

11/13/2019 7:21:10 AM


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 (4kcal/gm), fat (9kcal/gm) and protein (4kcal/gm) found in food.  Therefore, studies have defined low carbohydrate as a percent of daily macronutrient intake or total daily carbohydrate load.  We will define it here as:

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

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


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 approaches in producing rapid weight loss for the first 6-12 months.[4][5][6]  While diets inducing weight-loss produces 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 then reduces hunger and overall food intake and produces a caloric deficit.  Additionally, 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 version of low-carb, deserves mention.  Keto diets restrict carbohydrate to induce nutritional ketosis and typically limits carbs to 20-50gms daily.  Restricting carbs to under 50gms 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 can is measurable as serum or urinary ketones.  Nutritional ketosis generally increases serum ketones to 1mmol/L to 7mmol/L but does not produce metabolic acidosis.  Diabetic ketoacidosis by definition, includes metabolic acidosis, hyperglycemia and serum ketones (generally over 20 mmol/L).[9]

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

There are several hypothetical concerns of the long-term safety of low-carb diets that deserve mention. Safety concerns of low-carb diets relate to ketosis, long-term cardiovascular safety, lipid, and renal effects.


Nutritional ketosis can be induced in the keto diet, the induction phase, and any time where carb load is limited to < 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 remain safe in patients, even with type 2 diabetes.[9][10]  While there have been cases of DKA with concomitant SGLT2 inhibitors in type 2 diabetics, it is unclear if the very low carb approach can put increased risk of DKA with SGLT2 use. However, the recommendation is for caution with the use of ketogenic diets with 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-analysis have shown an increased risk of mortality with carbohydrate intake < 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] Until long term, randomized studies can be undertaken, the long-term effect is unclear.

Lipid Response

Incorporating more fat and protein in response to reduction of dietary carbs has led to concerns on the effect of low-carb dieting on lipids; specifically, LDL cholesterol.  Recent systematic reviews of low-carb diets on lipids demonstrate a neutral to small increase in LDL, but a favorable triglycerides reduction and an increase in HDL cholesterol; particularly those assigned to the very low-carb intervention.[15][16] Although not formally studied, there may be a subset of lean individuals who have a hyper LDL response with ketogenic diets; a term coined Lean Mass Hyper-Responders (https://cholesterolcode.com/lmhr; accessed December 26, 2018). 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 on renal function.  However, depending on specific goals, athletes should ingest protein loads to optimize muscle protein synthesis (1.6 gm/kg) or for endurance sports, (0.8 gm/kg).[17][18] 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.[19]  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.[20]

Clinical Significance

The study of low-carb diets has centered on weight loss in obese and overweight people as well as 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

By far the most research in low-carb approaches has shown that low-carb diet, and specifically ketogenic approaches, induces rapid induction of weight loss.  Initial weight loss is due partly from water loss, but fat loss occurs with adherence to the low carb approach.  With all dietary intervention, as adherence to the diet wanes, weight loss effect becomes similar to other dietary approaches after 1 year.[21] It is notable that most of the low-carb studies generally use an ad-libitum approach of caloric intake (limiting carbs instead), while most comparison diets are calorie restricted.  In general, shared decision making is a valid and person-centered approach in determining nutritional approaches to 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.[22]  A recent study demonstrated a significant reduction of insulin and oral medications and A1C reduction with ketogenic approaches while demonstrating a high adherence to the intervention at 12 months.[23][24] Also markers of cardiometabolic risk factors improved.[25]  Approaches to nutritional lifestyle approaches to diabetes, (medical nutrition therapy) have included low carb as an option in recent guidelines.[26][27]  Recent prospective and randomized controlled trials have demonstrated a consistent benefit in glycemic control, weight loss and sustained medication reduction using a very low carb approach (< 14% of energy from carbohydrates).[28][29][30]

Cardiovascular Risk Factors

As mentioned above, the effect of low-carb diets on cardiovascular risk factors continue 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 TG, increases in HDL, have been demonstrated with low-carb diets.[4][25][16]

Other Issues

Ketogenic diets have been used successfully since 1920 before the existence of medications for epilepsy.[9][31]  Recent studies have shown that acne, cancer, non-alcoholic fatty liver disease, polycystic ovary syndrome, and Alzheimer disease may improve with ketogenic diets.[9][32]  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 recreational population have also undergone testing.[33][34]

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 health or athletic performance, weight loss, improvement of glycemic control for Type 1 or 2 Diabetes, or for a seizure disorder.

  • First, an understanding of what macronutrients are and its relation to food is a critical part of the 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 (< 45% carbohydrates) level.
  • A way to initiate low-carb is through a rapid induction phase of 2 to 4 weeks with 20 to 50gms 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 adverse response. 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 are prudent with rapid reductions in fasting glucose. Evidence Levels: IV

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Low Carbohydrate Diet - Questions

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A patient reports that she has lost 40 pounds over the past month by following a very low carbohydrate diet with less than 50 gm of carbohydrates daily. Limited bread, pasta, or potatoes are allowed, but meat, seafood, and vegetables can be included, ad libitum until satiated. Which of the following is true about this diet?

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A 65-year-old male comes for a routine health visit. He has no active complaints. His past medical history is significant for dyslipidemia but does not take any medications. His family history includes type 2 diabetes in his father. His blood pressure today is 130/65 mmHg and pulse of 74 bpm. His BMI is 33, with a waist circumference of 41 inches. His physical exam is normal. With his risk factor of type 2 diabetes, fasting glucose, HbA1c, and lipid panel are ordered. His labs return with fasting glucose: 110 mg/dl, hemoglobin A1c of 5.9%, total cholesterol = 256 mg/dl, LDL cholesterol = 146 mg/dl, HDL cholesterol= 39 mg/dl, and triglycerides = 174 mg/dl. His cardiovascular risk is calculated to be less than 5%. He is counseled on lifestyle changes such as diet modification and aerobic exercise. He is considering initiating a low-carbohydrate diet. Which of the following effect will this diet have on his cardiovascular risk?

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A 45-year-old man with type 2 diabetes comes for a routine check. He mentions that his blood sugars are still elevated in the morning, with fasting blood glucose of 190 mg/dl on average. He is taking his metformin 1000 mg twice a day as prescribed as well as atorvastatin 40 mg and lisinopril 20 mg daily. His BMI today is 38, and his weight has been increasing despite his diet and exercise. Today, his blood pressure today is 118/78 mmHg, and his hemoglobin A1c is 8.7%. He would like to know what he can do to improve his sugars without medications. He does not want to try insulin. He is willing to try a different diet and continue his exercise. He has heard a lot about the ketogenic diet and asks for advice. Which of the following affect will a low-carbohydrate, ketogenic diet have on this patient?

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Low Carbohydrate Diet - References


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