Effect of Candida Rugosa Lipase on Serum Triglyceride Lowering
Condition: Hypertriglyceridemia
MeSH terms: Hypertriglyceridemia
Study type: Interventional

Summary: 
      The primary objective of this study was to evaluate the safety and tolerability of 3 doses of
      fungal lipase in the treatment of adults with mildly elevated serum triglycerides. The
      secondary objective was to assess the efficacy of fungal lipase in reducing serum
      triglycerides in adults with mildly elevated serum triglycerides.
    

Detailed description: 
      According to the World Health Organization, ischemic heart diseases and stroke were the
      leading causes of death globally in 2019, accounting for 16% and 11% of the world's total
      deaths, respectively. The American Heart Association reported in 2020 that approximately 87%
      of all strokes are ischemic strokes, in which blood flow to the brain is blocked (Virani et
      al). That blockage is typically caused by an accumulation of fatty deposits inside
      triglycerides (atherosclerosis). Higher levels of serum triglycerides are linked to an
      increased risk of ischemic stroke in men and women. Researchers tracked 7,579 women and 6,372
      men whose triglyceride and cholesterol measurements were taken in the late 1970s. Subjects
      were followed for up to 33 years. During the follow-up period, 837 women and 837 men
      developed ischemic stroke. Both men and women had a higher risk of stroke with high levels of
      triglycerides, in particular triglyceride levels of 5 mmol/L (443 mg/dL or 5.0 mmol/L) or
      more. These individuals carried four-fold greater stroke risk than those with lower levels
      (Varbo et al).

      Each of the current treatments for hypertriglyceridemia has negative side effects and
      therefore many individuals that suffer from this condition decline treatment to reduce stroke
      risk. Oral supplementation with a fungal lipase preparation from Candida cylindracea
      (formerly rugosa), commonly found in dietary supplements for digestive health, is a candidate
      strategy to lower triglycerides without side effects.

      During digestion, each of lingual, gastric, and pancreatic lipases combine to remove the
      outer 2 fatty acids from ingested, dietary triglycerides, thus forming monoglycerides and 2
      free fatty acids. Following uptake by intestinal enterocytes, the free fatty acids are
      re-esterified with the monoglycerides to reform triglycerides before release in to the
      bloodstream. Overconsumption of dietary fats can thus lead to elevated levels of serum
      triglycerides.

      Candida cylindracea (formerly rugosa) lipase, however, hydrolyzes all three fatty acids from
      dietary triglycerides to release free fatty acids and the glycerol backbone. It is predicted
      that most of these free fatty acids and glycerol molecules enter the bloodstream without
      reformation to triglycerides by the major metabolic pathway to reform the triglycerides from
      monoglycerides. Nonetheless, an alternate metabolic pathway to generate triglycerides from
      free fatty acids alone does exist in enterocytes.

      The investigators tested the hypothesis that fungal lipase-mediated lowering of dietary
      monoglycerides would lower serum triglyceride levels in a randomized, double-blind, placebo
      controlled parallel arm clinical trial of 39 subjects with elevated serum triglyceride
      levels. Subjects were between 18 and 75 years of age, with good general health and mildly
      elevated serum triglycerides (150 mg/dL to 500 mg/dL, or 1.7 mmol/L to 5.6 mmol/L). The study
      included 4 study site visits over a 13 to 16 week period (including baseline period).

      Subjects underwent an initial phone screen and were asked questions regarding their age and
      general health. Eligible subjects were scheduled for a screening visit. Subjects attend all
      visits in a fasted state. At the screening visit (Visit 1), the inclusion and exclusion
      criteria were reviewed and the overall details of the study were explained and informed
      consent was obtained. Blood pressure, body weight, and body mass index (BMI) were measured.
      Family and medical history and general health were recorded.

      A fasting blood sample was collected and serum triglycerides were measured. Subjects with
      serum triglyceride levels between 151 mg/dL (1.71 mmol/L) and 499 mg/dL (5.65 mmol/L) were
      invited to participate in the study. Eligible subjects were scheduled to return to the study
      site within 4 weeks for their baseline visit (Visit 2).

      At Visit 2, a fasting blood sample (12 mL) was collected for glucose, electrolyte,
      triglyceride, cholesterol (including HDL, LDL, VLDL), liver and kidney function, and HbA1C
      measurements. Subjects were randomized to one of 4 arms: 1) placebo (n = 9), 2) 1X low-dose
      (n = 10), 3) 2X medium-dose (n = 10), and 4) 3X high-dose (n = 10). Subjects were provided
      with a 90 day supply of investigational study product (lipase or placebo) and were instructed
      to take one dose with each major meal (3 doses per day) for the next 90 days. Subjects were
      instructed to follow their standard diet and exercise routine for the duration of the study.
      Subjects were scheduled to return to the study site after 30 days (+/- 4 days) for Visit 3.

      At Day 30 (Visit 3), a fasting blood sample (12 mL) was collected for glucose, electrolytes,
      triglyceride, cholesterol (including HDL, LDL, VLDL), liver and kidney function, and HbA1C
      measurements. Subjects were scheduled to return to the study site for the 4th and final visit
      at Day 90. At Day 90, a fasting blood sample (12 mL) was collected for glucose, electrolyte,
      triglyceride, cholesterol (including HDL, LDL, VLDL), liver and kidney function, and HbA1C
      measurements. Subjects returned any unused study product and compliance was assessed.
    

Intervention name(s): Placebo; Candida cylindracea lipase (225,000 FIP lipase units per day); Candida cylindracea lipase (450,000 FIP lipase units per day); Candida cylindracea lipase (675,000 FIP lipase units per day)
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): Participants were directed to consume 1 placebo capsule containing maltodextrin, three times daily, for 90 days. Subjects were directed to consume the capsules with their three largest eating occasions of the day.; Participants were directed to consume 1 capsule containing lipase (75,000 FIP lipase units per capsule), three times daily, for 90 days. Subjects were directed to consume the capsules with their three largest eating occasions of the day.; Participants were directed to consume 2 capsules containing lipase (75,000 FIP lipase units per capsule), three times daily, for 90 days. Subjects were directed to consume the capsules with their three largest eating occasions of the day.; Participants were directed to consume 2 capsules containing lipase (112,500 FIP lipase units per capsule), three times daily, for 90 days. Subjects were directed to consume the capsules with their three largest eating occasions of the day.
Other intervention name(s): GFA-918; Candida rugosa lipase; GFA-918; Candida rugosa lipase; GFA-918; Candida rugosa lipase
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: triglyceride; lipase; cholesterol; cylindracea; rugosa; digestion; triacylglycerol