Abstract

Background: Multi-vitamin multi-mineral (MVMM) products often come in several single-substance capsules from different manufacturers. However, attempts to mix several vitamins and minerals into one MVMM product have been complicated and often involve legal concerns. This study aimed to comparatively investigate the changes in laboratory parameters and the quality of life (QOL) among individuals who received different MVMM formulations. Methods: This three-arm non-randomized controlled trial was conducted at VitalLife Scientific Wellness Center (VSWC), Bangkok, Thailand. A total of 72 healthy adult individuals with total serum 25-(OH)D level of 20-29 ng/ml were invited to choose from the three available options, namely, (1) Hydro-Cell-Key (HCK®, Hepart AG, Switzerland) contains vitamin D3 2,000 IU, vitamin C 1,000 mg, vitamin E 166 mg, vitamin A 1 mg, coenzyme Q10 30 mg, natural carotenoids 8 mg, and citrus flavonoids 200 mg in granule formulation; (2) VTL-7 (VWSC) contains similar vitamins and minerals but in capsule formulation; and (3) placebo capsule (no supplement). The 36-Item Short-Form Health Survey (SF-36) was used to measure QOL at baseline, month 3 and 6. A generalized estimating equation (GEE) was used to compare the repeated-measure outcomes across the three groups. This study was registered at the Thai Clinical Trial Registration (TCTR20190205002) and approved by the Bumrungrad International Institutional Review Board (BI-IRB No.258-10-18PhFub). Results: Both VTL-7 and HCK saw a significantly higher increase in vitamin D than placebo at months 3 and 6, i.e., VTL-7 from 25.15 ± 2.13 to 35.53 ± 6.11 (p < 0.001) and 33.38 ± 6.89 (p < 0.001); HCK from 24.25 ± 3.08 to 28.43 ± 5.93 (p = 0.005) and 27.40 ± 5.24 (p = 0.012); and placebo from 24.00 ± 2.73 to 23.05 ± 4.39 (p = 0.273) and 22.30 ± 6.23 (p = 0.200), respectively. Similarly, β-carotenoids of VTL-7 vs. HCK groups significantly increased from 0.88 ± 0.68 vs. 0.94 ± 0.55 at baseline to 3.03 ± 1.79 (p < 0.001) vs. 1.09 ± 0.61 (p = 0.125) and 3.26 ± 1.74 (p < 0.001) vs. 1.15 ± 0.66 (p = 0.064), respectively. These findings were corroborated through the GEE analysis. Other micronutrients at months 3 and 6 did not increase significantly from baseline in any group. The overall QOL among the three groups in terms of physical (p = 0.560) and mental (p = 0.750) health increased but was not statistically significant. Conclusion: The supplements of MVMM in capsule formulation increased the serum levels of some micronutrients to a higher extent than that of granule formulation. Participant adherence remains a potential confounder and should be further explored. Clinical Trial Registration: identifier: TCTR20190205002.

Abstract

It is well known, based on the previous research, that a ketogenic diet leads to an improvement in the lipid profile and decreases cardiovascular risk factors such as hypertension. However, recent studies have also reported increased levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C) as a result of this diet. It has been postulated that this elevation in LDL-C would not likely increase cardiovascular complications due to the large LDL-C particle size. In this case report, we present a case of a rapid increase, followed by a rapid correction of LDL-C, in a patient following a ketogenic diet. A 56-year-old Hispanic female with a past medical history of hypertension and fibromyalgia presented to the outpatient clinic for evaluation of fatigue. She reported that she had been following a strict ketogenic diet along with daily regular exercise for approximately 30-40 days prior to this visit. Her diet consisted of low-carbohydrate vegetables, seafood, avocados, eggs, and coconut oil. The patient's physical exam was unremarkable. At the time of the visit, her BMI was calculated at 28 kg/m2, with a weight loss of approximately six to seven pounds since starting the ketogenic diet. Her fasting lipid profile showed a total cholesterol of 283 mg/dl, LDL-C of 199 mg/dl, high-density lipoprotein cholesterol (HDL-C) of 59 mg/dl, and triglycerides levels of 124 mg/dl. She was instructed to stop the ketogenic diet and to incorporate a balanced diet, which includes a higher amount of carbohydrates and lower fat. She was also started on high-intensity atorvastatin. However, she reported experiencing myalgias soon after initiating atorvastatin; therefore, the medication was switched to rosuvastatin 10 mg at bedtime. During her follow-up appointment, she reported not having consistently taken rosuvastatin due to the concern of worsening myalgias. Her lipid profile, after four weeks of ketogenic diet discontinuation and inconsistent use of statins, showed significant improvement resulting in a total cholesterol level of 190 mg/dl and LDL-C of 106 mg/dl. Statin therapy was discontinued, and the patient maintained optimal LDL-C levels on subsequent testing. This patient showed a rapid increase in LDL-C and total cholesterol after only 30-40 days of the ketogenic diet. Her drastic elevation in LDL-C could also be explained due to the rapid weight loss, as cholesterol in the adipose tissue is known to mobilize as the fat cells shrink. Interestingly, her BMI four weeks after the discontinuation of the ketogenic diet did not change despite a marked improvement in her LDL-C. Therefore, we believe the acute onset and resolution of hyperlipidemia was secondary to the ketogenic diet itself. This study helps to better understand expectations when recommending a ketogenic diet to patients and its consequences. There is currently no statistically significant study that proves this elevation of LDL-C would not increase cardiovascular risks. Furthermore, the necessity for statin therapy in a ketogenic diet-induced hyperlipidemia remains unknown.