Introduction. The multifactorial chylomicronemia ((MCM), also known as type V hyperlipoproteinaemia or mixed hyperlipidaemia) is an oligogenic or polygenic disorder that is associated with a reduction in lipoprotein lipase activity which leads to chylomicronemia. In this disease, very high concentrations of serum triglycerides (≥10 mmol/l (≥880 mg/dL)) can be observed in the fasting state due to the accumulation of both VLDL-C and chylomicron. In patients with MCM, chylomicronemia typically occur in adulthood and is exacerbated by the presence of secondary factors such as a diet rich in dietary fats and simple sugars, obesity, alcohol intake and uncontrolled diabetes. It has been estimated that chylomicronemia can be found in 1:600 adults. However, it is likely that the prevalence of MCM may increase in the future due to the increasing prevalence of obesity, metabolic syndrome and type 2 diabetes. This condition increases the risk of acute pancreatitis, which can be recurrent and potentially fatal. Indeed, the risk of acute pancreatitis is 10-20% for TG levels > 22.58 mmol/L (>2000 mg/dL). Furthermore, because MCM patients often present with other lipid disturbances as well as a worse metabolic profile, these patients are at increased risk of cardiovascular disease (CVD). Fortunately, MCM patients generally respond well to modifications in lifestyle, to treatment of secondary factors and to triglycerides lowering therapies such as fibrates. However, it is still unknown which kind of diet has the greatest effect on triglycerides level and on the metabolic profile in MCM patients.

The nutritional recommendations can be very different according to the nature of the patient's population to be treated. In order to reduce and manage triglycerides level in the general population, the American Heart Association guidelines recommend reduction of simple carbohydrates intake.

On the other hand, the nutritional intervention strategy is quite different for subjects affected by familial chylomicronemia syndrome (FCS), for which the treatment focuses on restriction of dietary fat. FCS is a very rare autosomal recessive disease that leads to a drastic reduction of chylomicrons clearance leading to chylomicronaemia. Therefore, a very strict lipid-controlled diet low in long-chain fatty acid (10-30g/day or 10%-15% of total energy intake) is required in order to lower chylomicron formation.

MCM is a complex condition in which both an increased VLDL formation by the liver and a decreased chylomicrons and VLDL clearance are present. Furthermore, triglycerides values are fluctuating from day to day but generally remain very high. Therefore, the best dietary approach for these patients remains to be elucidated.

Primary Objective. The primary objective of this study is to compare the effects of low-fat vs low-carbohydrate diets on fasting serum triglyceride concentrations.

Secondary Objectives.

1. To compare the effects of low-fat vs low-carbohydrate diets on other fasting cardiometabolic parameters: measured LDL-C, total cholesterol, HDL-C, glucose, insulin, HOMA-IR, apoB, non-HDL-C, hs-CRP, PCSK9 and free fatty acids (FFA).
2. To compare the effects of low-fat vs low-carbohydrate diets on SBP, DBP and waist circumference.
3. To compare the effects of low-fat vs low-carbohydrate diets on lipoprotein subfractions (fasting).
4. To compare the effects of low-fat vs low-carbohydrate meals on postprandial triglycerides, insulin, glucose, FFA and PCSK9 after a standardized test meal.
5. To assess the patients' appreciation, compliance and tolerability for each experimental diet (feedback questionnaire).

Inclusion Criteria:

1. Men or women ≥ 18 years.
2. Fasting triglycerides values ≥ 10 mmol/L (≥ 880 mg/dL) at least once, with or without medication.
3. Fasting triglycerides values ≥ 6.0 mmol/L at screening.

Exclusion Criteria:

1. A diagnosis of familial chylomicronemia syndrome, familial hypercholesterolemia or type III hyperlipidemia.
2. An episode of accute pancreatitis in the 6 months prior the screening.
3. Recent changes (in the last 3 months) in medication or supplement known to affect glucose metabolism such as steroid or oral contraceptive.
4. Recent changes (in the last 4 weeks) in lipid-lowering medication such as fibrates and statins.
5. Any condition known to affect lipid or glucose metabolism such as uncontrolled hypothyroidism or Cushing's syndrome.
6. Major surgery in the 3 months preceding the study.
7. Significant weight change (±10 %) within 3 months prior to beginning the study.
8. Inability to reduce alcohol use (0-2 units per week).
9. The necessity or the wish to follow a specific diet.
10. BMI ≥ 40 kg/m2.
11. Breastfeeding woman.
12. Pregnancy or the wish to become pregnant.
13. Consumption of dietary supplements such as omega-3, psyllium or phytosterols.
14. Any serious health condition associated with a life expectancy of ≤ 1 year.