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Is an increased anion gap seen with intermittent fasting and/or a low carb diet?

Intermittent fasting refers to various regimens that restrict dietary intake via alternate day fasting, calorie restriction on schedule days, eating within a specific timeframe, or fasting protocols for religious purposes.

  • Human and animal research suggests that intermittent fasting can help promote weight loss, improve glucose and insulin regulation, and have some beneficial effects on inflammatory markers, adiponectin, and leptin.
  • Research from NHANES studies suggests that restricting nighttime eating (after 5pm) to less than 30% of total calories significantly improved HbA1c and CRP in women.
  • 11 of 16 intervention trials reviewed resulted in weight loss using intermittent fasting
  • Alternate-day fasting is not superior to restricted time eating and was associated with intense hunger on fasting days.
  • Further human research must be done to confirm clinical outcomes associated with intermittent fasting, diabetes, cardiovascular disease, or other chronic diseases.
  • Intermittent doesn’t appear to be associated with changes in anion gap and is different from “low carb” diets which can be detrimental.

A “low carb” diet that is not medically necessary (e.g., cancer therapy, intractable seizures, other neurodegenerative disorders) can be detrimental. Effects can progress from ketosis to ketoacidosis which is characterized by a decrease in pH, decreased serum bicarb, and electrolyte abnormalities, so you will see an increased anion gap. If not corrected, ketoacidosis can lead to acute pancreatitis, hypoglycemia, and dyslipidemia, especially in diabetics.    

 Blanco, Joanna C et al. “Starvation Ketoacidosis due to the Ketogenic Diet and Prolonged Fasting - A Possibly Dangerous Diet Trend.” The American journal of case reports vol. 20 1728-1731. 22 Nov. 2019.

It’s important to define “low carb” and what that translates into:

  • Very low-carbohydrate (< 10% carbohydrates) or 20-50 gm/day
  • Low-carbohydrate (<26% carbohydrates) or less than < 130 gm/day
  • Moderate-carbohydrate (26%-44%)
  • High-carbohydrate (45% or greater)
  • The Institute of Medicine proposes Americans obtain 45%-65% of calories from carbohydrates
  • Epidemiological studies and meta-analysis have shown an increased risk of mortality with carbohydrate intake <40%.
  • Restricting carbohydrate intake to less than 50 grams/day depletes glycogen stores and stimulates ketone production from stored fat.
  • Nutritional ketosis can increase serum ketones to 1-7 mmol/L without metabolic acidosis while diabetic ketoacidosis is characterized by serum ketones over 20 mmol/L.

Oh, Robert, et al. “Low Carbohydrate Diet.” StatPearls, StatPearls Publishing, 9 July 2020.

Note that the RDA for carbohydrate is 130 grams per day, representing the amount of glucose the brain uses on a daily basis for adults and children.    

Slavin, Joanne, and Justin Carlson. “Carbohydrates.” Advances in nutrition (Bethesda, Md.) vol. 5,6 760-1. 14 Nov. 2014

High anion gap metabolic acidosis was diagnosed in a 31-year old man following a low carbohydrate (less than 20 grams/day) for one week. He presented with serum bicarbonate of 9.2 mEq/L, anion gap of 20 mEq/L, blood glucose of 86 mg/dL, serum ketones 2+, and serum lactate 1.4 mEq/L, shortness of breath, and palpitations.        

Basnet, Sijan et al. “Severe anion gap metabolic acidosis associated with initiation of a very low-carbohydrate diet.” Journal of community hospital internal medicine perspectives vol. 9,2 165-167. 12 Apr. 2019

Although weight loss may be associated with low carb diets, the risks may outweigh the benefits.