Study Finds Ketogenic Diets May Increase “Bad” Cholesterol

The ketogenic (keto) diet may have long lasting effects on the gut microbiome and cardiovascular health (CVH), according to a trial published in Cell Reports Medicine. Although the diet is associated with short-term weight loss, the authors found it may decrease glucose tolerance, increases skeletal muscle PDK4, and reduces AMPK and GLUT4 levels.^1,2

Keto diets are characterized as the significant reduction in carbohydrate intake and the emphasis on fat consumption, which forces the body into ketosis. Image Credit: © nadianb - stock.adobe.com

Millions of individuals in the US have high cholesterol, which is defined as having a total cholesterol level above 200 mg/dL. High levels of low-density lipoproteins (LDLs), commonly referred to as “bad” cholesterol, leads to plaque buildup and narrowing of the arteries, resulting in decreased blood flow to the heart and other organs. Individuals with high LDL levels are at an increased risk of heart disease and stroke, the 2 leading causes of death in the US.³

Keto diets are characterized as the significant reduction in carbohydrate intake and the emphasis on fat consumption, which forces the body into ketosis. The diet relies on ketone bodies produced from stored fat by the liver as a source of energy. A typical keto diet has a high fat requirement, which could include 165 grams of fat in a daily 2000 calorie diet, and supplies as much as 90% of daily calories. Protein is another part of the keto diet but there is little discrimination between lean protein sources and those high in saturated fats. In fact, eating too much protein can interfere with reaching a state of ketosis.^4,5

Keto diets are not suited for every individual and are associated with various potential health risks including nutrient deficiency—due to decreased intake of fruits and vegetables, which are necessary sources of vitamins, minerals, antioxidants, and fiber—liver and kidney issues, constipation, and mood swings.^4,6

Due to the specific requirements of keto diets, patients need access to information resources that effectively guide them through safe implementation of this diet. Pharmacists are key resource points to navigate the nuances of keto diets and chronic health management, such as providing information about monitoring urinary ketones or identifying the carbohydrate content of prescribed medications. Additionally, keto diets often require vitamin supplementation due to the decreased intake of fruits and vegetables. The study authors findings support and contribute to existing research indicating potential health risks associated with ketogenic diets, helping pharmacists and patients weigh the potential risk-benefit of implementing this diet into a treatment plan.⁷

The current study evaluated 60 healthy adults aged 18 to 65 who completed ≥4 weeks of either MODSUG (n = 18), LOWSUG (n = 17), or LOWCHO (n = 18) diet. Of the participants, 53 completed the 12-week diet intervention. The authors randomized them into 3 groups based on self-reported carbohydrate intake: a ketogenic group, who reported less than 8% of daily calories from carbohydrates; a low-sugar group, who reported less than 5%; and a control group, who reported approximately 18%.¹

According to the data, a low-sugar diet was associated with minimal affects to metabolism or the gut microbiome and a decrease in LDL cholesterol (LDL-C). Keto diets were associated with decreased glucose tolerance, increases skeletal muscle PDK4, and reduces AMPK and GLUT4 levels. At week 4, participants from the keto group had reduced fasting glucose and increased apolipoprotein B, C-reactive protein, and postprandial glycerol concentrations. At 12 weeks, there were no significant impact on CVH during the study, but there was a sustained decrease in gut microbiome diversity. In contrast, participants on the low-sugar diet achieved reductions in body fat and total cholesterol, especially LDL-C, without a negative impact on their gut microbiome.¹

The findings reinforce existing recommendations that advise a low-sugar diet to lower the risk of cardiovascular disease and other chronic health conditions. Due to the potential risks associated with a keto diet, it may not be an appropriate nutritional plan for every patient. This information provides pharmacists with deeper knowledge about the effects of ketogenic diets, aiding them in tailoring personalized treatment plans that have the patients needs at the center.

REFERENCES

1. Hengist A, Davies R, Walhin J, et al. Ketogenic diet but not free-sugar restriction alters glucose tolerance, lipid metabolism, peripheral tissue, phenotype, and gut microbiome: rct. Cell Rep. August 5, 2024. doi:10.1016/j.xcrm.2024.101667

2. Keto diet may increase 'bad' cholesterol, reduce bacterial diversity in the gut. Medical News Today. August 12, 2024. Accessed August 20, 2024. https://www.medicalnewstoday.com/articles/keto-diet-may-increase-bad-cholesterol-reduce-bacterial-diversity-in-the-gut

3. About cholesterol. CDC. May 14, 2024. Accessed August 20, 2024. https://www.cdc.gov/cholesterol/about/index.html

4. Should you try the keto diet? Harvard Health Publishing. March 28, 2024. Accessed August 20, 2024. https://www.health.harvard.edu/staying-healthy/should-you-try-the-keto-diet

5. Ketosis. Cleveland Clinic. August 15, 2022. Accessed August 20, 2024. https://my.clevelandclinic.org/health/articles/24003-ketosis

6. Health benefits of fruits and vegetables. National Library of Medicine. July 6, 2012. Accessed August 20, 2024. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649719/

7. Bainbridge J, Gidal B, Ryan M. The Ketogenic diet. Pharmacotherapy. 1999. https://www.accp.com/docs/positions/opinionPapers/pos20.pdf