Genes restrict Vitamin D, Vitamin K, Omega-3, Magnesium, etc.

Genetic Restrictions in Nutrient Metabolism: Population Impact Analysis
VitaminDWiki – Genetics category contains

Genetic Restrictions in Nutrient Metabolism: Population Impact Analysis

Perplexity AI - Deep Research April 2025
This report examines the genetic factors that restrict nutrient metabolism, absorption, transport, and function for five key nutrients. For each nutrient, we identify the relevant genes involved and estimate the percentage of the population affected by genetic variations that may limit optimal nutrient utilization.

Vitamin D: The Sunshine Nutrient

Key Genetic Factors Restricting Vitamin D

VDR (Vitamin D Receptor): Contains several polymorphisms including FokI, BsmI, ApaI, and TaqI that affect receptor function and sensitivity [1] [19]
CYP2R1: Converts vitamin D to 25(OH)D (calcidiol), the main circulating form [2] [13]
CYP27B1: Converts 25(OH)D to the active 1,25(OH)₂D (calcitriol) [2] [20]
CYP24A1: Catalyzes vitamin D catabolism, affecting vitamin D levels [13] [20]
GC: Encodes Vitamin D Binding Protein (VDBP), critical for vitamin D transport [2] [13]
DHCR7: Involved in vitamin D synthesis pathway from 7-dehydrocholesterol [13] [20]

Population Affected – 40-50% at blood level (higher % at cellular level)

Approximately 40-50% of the general population shows some genetic predisposition to vitamin D insufficiency. In specific populations, the prevalence varies significantly:
- Female children (53.1%) have higher rates than male children (41.75%) [3]
- Individuals with specific genetic variants in the top quartile of risk scores have 2-2.5 fold higher odds of vitamin D insufficiency [13]
- Vitamin D deficiency is particularly prevalent in Middle Eastern and Asian populations [1]

Magnesium: The Essential Mineral

Key Genetic Factors Restricting Magnesium

TRPM6: Encodes a magnesium-permeable ion channel critical for intestinal absorption and renal reabsorption [4] [5]
TRPM7: Regulates cellular magnesium homeostasis and is ubiquitously expressed [5] [14]
CNNM4: Mediates basolateral magnesium extrusion in intestinal cells [5]

Population Affected – 20-30%

Approximately 20-30% of the population carries genetic variants potentially affecting magnesium metabolism:
- About 31.5% are heterozygous for the rare G allele of rs2274924 in TRPM6 [4]
- Approximately 22% are heterozygous for the A allele of rs3750425 in TRPM6 [4]
- Population frequencies of these variants range from 7-21% for rs3750425 A allele and 15-36% for rs2274924 G allele across different ethnic groups [4]

Vitamin K: The Coagulation Vitamin

Key Genetic Factors Restricting Vitamin K

VKORC1 (Vitamin K Epoxide Reductase Complex Subunit 1): Particularly the 1173C>T polymorphism affects vitamin K recycling and utilization [6] [15]

Population Affected

A substantial portion of the population carries genetic variants affecting vitamin K metabolism:
- The T allele frequency of VKORC1 1173C>T polymorphism is 38.8% in studied populations [15]
- Approximately 62.8% of individuals carry at least one T allele (48% heterozygous CT and 14.8% homozygous TT) [15]
- Carriers of the T allele have a 19% increased risk of aortic calcification, suggesting impaired vitamin K-dependent protein function [15]

Vitamin C: The Antioxidant Nutrient

Key Genetic Factors Restricting Vitamin C

SLC23A1: Encodes SVCT1, the sodium-dependent vitamin C transporter responsible for dietary absorption and renal reabsorption [7] [16]
SLC23A2: Encodes SVCT2, responsible for cellular vitamin C accumulation [8] [16]

Population Affected – varies

While the exact percentage is difficult to determine from available data, genetic variations affecting vitamin C transport appear common:
- The rs1279683 SNP in SLC23A2 is significantly associated with lower plasma vitamin C concentrations in carriers of the GG genotype [17]
- Approximately 15-25% of studied populations carry genetic variants in SLC23A2 that may affect vitamin C accumulation in tissues [8]
- Variants in SLC23A2 have been associated with increased disease risk when combined with low vitamin C intake [8]

Omega-3 Fatty Acids: The Essential Fats

Key Genetic Factors Restricting Omega-3

FADS1 (Fatty Acid Desaturase 1): Involved in the biosynthesis of highly unsaturated fatty acids [9] [10]
FADS2 (Fatty Acid Desaturase 2): Critical for conversion of essential fatty acids to longer-chain polyunsaturated fatty acids [9] [18]

Population Affected - wide: 1% to 55%

The prevalence of genetic restrictions varies widely by ancestry:
- TT genotype at rs174537 (associated with limited LC-PUFA biosynthesis) ranges from <1% in African-ancestry populations to 40-55% in high Amerind-ancestry Hispanic populations [10]
- Approximately 11% of European-ancestry populations carry the TT genotype [10]
- The frequency of minor alleles in FADS polymorphisms ranges from 22.7% to 32.2% among pregnant women in studies [18]
- AI ancestry accounts for approximately 12% of variation in EPA, DHA, and ARA levels in Hispanic populations [10]

Conclusion

VitaminDWiki – Genetics category contains

346 articles in the Genetics category

see also

Vitamin D Receptor has 540 items
Vitamin D Binding Protein = GC has 178 items
CYP27B1 has 64 items
CYP24A1 in title of 39+ items
CYP2R1 25+ items
Calcidiol has 49 items
Calcitriol has 64 items
Topical Vitamin D
Nanoemulsion Vitamin D may be a substantially better form
1289 genes changed with higher doses of Vitamin D - RCT Dec 2019
CYP3A4 (7 as of Dec 2022)
Getting Vitamin D into your blood and cells

Vitamin D blood test misses a lot
in Visio for 2023

Vitamin D from coming from tissues (vs blood) was speculated to be 50% in 2014, and by 2017 was speculated to be 90%
Note: Good blood test results (> 40 ng) does not mean that a good amount of Vitamin D actually gets to cells
A Vitamin D test in cells rather than blood was feasible (2017 personal communication) Commercially available 2019
- However, test results would vary in each tissue due to multiple genes
Good clues that Vitamin D is being restricted from getting to the cells
1) A vitamin D-related health problem runs in the family
    especially if it is one of 51+ diseases related to Vitamin D Receptor
2) Slightly increasing Vitamin D shows benefits (even if conventional Vitamin D test shows an increase)
3) DNA and VDR tests - 100 to 200 dollars $100 to $250
4) PTH bottoms out ( shows that parathyroid cells are getting Vitamin d)
   Genes are good, have enough Magnesium, etc.
5) Back Pain
   probably want at least 2 clues before taking adding vitamin D, Omega-3, Magnesium, Resveratrol, etc