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. 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 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.
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%.
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. Until long term, randomized studies can be undertaken, the long-term effect is unclear.
Incorporating more fat and protein in response to the 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. 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. Due to the varied and individualized response, recommendations are for baseline fasting lipid profile, periodic testing, and shared decision making.
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). 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.
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.