Ketogenic Diet and Vitamin D Metabolism: What Do We Know
Estimated reading time: 6 minutes
A review came out doing its best to investigate the effects of Ketogenic Diets on vitamin D. Being a huge fan of both; I thought it would make an interesting blog post and contribute to my goal of you knowing all the ways you can feel better.
In this scientific review, published in Dec 2022, some experts dug deep into intervention studies and other factors that could effect the connection between Ketogenic Diets and vitamin D. They even took a look at gene-nutrient interactions! So I am going to unpack what they found so you can better understand how a ketogenic diet may influence your Vitamin D status.
The researchers found five studies done in healthy adults, one in subjects with type 2 diabetes, and seven in subjects with epilepsy that assessed the levels of vitamin D pre-and post-intervention. What did they find? Here is a summary for your convenience! ⬇️
First, we need to introduce some of the terms used in this part of the authors’ review. Let me introduce you to 25(OH)D and 1,25(OH)2D. It will make reading this part easier to understand.
25(OH)D is the abbreviation for 25-hydroxyvitamin D. It is a blood test used to measure the level of vitamin D in your body. When vitamin D is absorbed by the body, it is converted into 25-hydroxyvitamin D (25(OH)D), which is the main circulating form of vitamin D in the blood. Measuring the level of 25(OH)D in the blood is considered the best way to assess a person’s vitamin D status.
1,25(OH)2D is the abbreviation for 1,25-dihydroxyvitamin D. It is the active form of vitamin D that is produced in the body through a series of metabolic reactions that involve the liver and kidneys. 1,25(OH)2D is a hormone that helps regulate the levels of calcium and phosphorus in the body, which are important for maintaining healthy bones.
Unlike 25(OH)D, which is considered the best marker for overall vitamin D status, 1,25(OH)2D levels are usually measured to evaluate certain medical conditions that affect calcium and bone metabolism, such as renal failure, hyperparathyroidism, and some rare genetic disorders.
What they found was that initially, low levels of vitamin D are often observed in Ketogenic Diet patients, but supplementation can increase vitamin D levels. The production of ketone bodies by the Ketogenic Diet creates an acidic environment that can inactivate liver and kidney hydroxylase, preventing the conversion of vitamin D to its active form. A hydroxylase is an enzyme that adds a hydroxyl group (-OH) to a substrate molecule, which is an important step in many biological processes, like Vitamin D conversion.
The authors discuss acidosis resulting from the production of ketone bodies that can decrease the vitamin D binding protein, reducing the amount of circulating active vitamin D. One of the evaluated studies cited showed that following a KD, 25(OH)D was increased, while 1,25(OH)2D was decreased, suggesting an effect of the KD on hydroxylase. But it was noted that 1,25(OH)2D has a short half-life and may not be a reliable index of vitamin D status.
And please note that a properly done ketogenic diet does not produce a chronic state of acidosis.
Individuals on ketogenic diets tend to consume more high-fat foods, which can lead to an increased dietary intake of vitamin D and higher levels of circulating vitamin D. One observational study they evaluated found that subjects following a low-carbohydrate/high-fat diet had significantly higher levels of 25(OH)D compared to those on an eastern European diet.
Fatty acids in the diet can also interact with cholecalciferol in intestinal absorption, and vitamin D supplementation is more effective when given with high-fat meals. Bile acids, increased after fat consumption, have been reported to activate vitamin D receptors.
Dietary intake of other macronutrients, such as protein, may also affect key metabolic enzymes of vitamin D. However, no data currently exist for the effects of Ketogenic Diets on these key metabolic enzymes.
In all studies that have assessed the effects of Ketogenic Diets (KDs) on vitamin D in healthy subjects, weight loss was present, which may have obscured the net effects of the Ketogenic Diets.
They found only one study that compared the effects of a KD versus another weight-loss diet (Mediterranean diet) on circulating 25(OH)D. And in that study, after weight loss via a very-low-carbohydrate Ketogenic Diet (VLCKD), the serum 25(OH)D concentrations increased significantly, while after the Mediterranean diet, the increase in vitamin D was not statistically significant.
This part is interesting and deserves some context because I don’t think it gets discussed enough. So I am going to do some explaining in a step-by-step manner. You won’t want to miss understanding this cool part!
The ketogenic diet (KD) is known to improve insulin sensitivity.
Insulin is a hormone that regulates blood sugar levels and has been reported to have effects on bone health and vitamin D metabolism.
Insulin has been shown to downregulate fibroblast growth factor 23 (FGF23), which is produced by bone cells and plays a key role in renal phosphate and vitamin D metabolism.
FGF23 is a hormone that physiologically inhibits α-hydroxylase, an enzyme responsible for converting vitamin D into its active form. It decreases the formation of active vitamin D.
Therefore, higher levels of FGF23 can lead to lower levels of active vitamin D.
Given that insulin can downregulate FGF23, increasing insulin sensitivity through a Ketogenic Diet could lead to reduced levels of FGF23 and potential increases in hydroxylated (active form) vitamin D.
This would suggest that Ketogenic Diets may actually have a positive impact on vitamin D metabolism.
Ketogenic diets have been proposed to modulate the gut microbiota by decreasing the abundance of Firmicutes and increasing the abundance of Bacteroidetes and microbial diversity.
This can have implications for vitamin D metabolism, as there is evidence that probiotics can increase circulating vitamin D levels and affect protein levels of vitamin D transporters, thereby promoting its absorption.
The authors reported that there really isn’t enough evidence on how gut microbiome changes on the ketogenic diet might affect Vitamin D levels.
Somebody get on that! I want to know! And in the meantime, we are going to continue to learn all the ways we can feel better. Let’s continue learning what we can from this excellent review!
Along with environmental factors, genetic variations in genes implicated in cholesterol synthesis, hydroxylation, and vitamin D transport can affect vitamin D levels.
A genetic SNP (single nucleotide polymorphism) is a common type of genetic variation that involves a single nucleotide change in the DNA sequence of a gene. It can influence how well we store, transport, or convert micronutrients into bioavailable forms.
Their review of the research identified 35 genes and several SNPs associated with vitamin D levels, suggesting that genetic variations can alter individual responses to ketogenic diets.
It’s part of why in my Brain Fog Recovery Program, I teach people how to do a nutrigenomics analysis so they can personalize their supplementation of Vitamin D and other important nutrients needed for optimal brain health.
So that was a LOT of information. Would you like to know the bottom line?
Here it is. In the majority of studies, increases in circulating vitamin D were reported.
Check it out yourself in the references if you are interested!
Detopoulou, P., Papadopoulou, S. K., Voulgaridou, G., Dedes, V., Tsoumana, D., Gioxari, A., … & Panoutsopoulos, G. I. (2022). Ketogenic Diet and Vitamin D Metabolism: A Review of Evidence. Metabolites, 12(12), 1288. https://doi.org/10.3390/metabo12121288