Why your genetics change what your supplements should be

Vitamin D: how well your cells respond

Vitamin D only works once it binds the vitamin D receptor inside your cells, which then switches on hundreds of downstream genes. The VDR gene builds that receptor. Four well-studied variants (FokI, BsmI, ApaI and one regulatory site) change how efficiently it responds, so two people with identical blood levels can get different biological effects from the same dose. Reduced-response genotypes need a higher level to reach the same activity. Jia et al., Genet Test Mol Biomarkers, 2013 (meta-analysis of 26 studies); Krasniqi et al., Nutrients, 2021 (systematic review, 77 studies).

Folate: whether folic acid is usable for you

MTHFR builds the enzyme that converts folic acid into methylfolate, the only form your body can put to work. Carry two copies of the 677T variant and that enzyme runs at roughly a third of normal speed. The folic acid in a standard multivitamin largely sits there unconverted. Methylfolate skips the broken step entirely, which is why your formula uses 5-MTHF rather than folic acid when your genotype calls for it. Tsang et al., Am J Clin Nutr, 2015 (systematic review and meta-analysis); Colson et al., Eur J Nutr, 2017.

Homocysteine: recycling it back to methionine

MTHFR and MTRR work with folate, B12, B6 and B2 to convert homocysteine back into methionine. Reduced-function variants slow that cycle, so homocysteine can drift upward on an ordinary diet. In a meta-analysis of 11,162 coronary heart disease cases against 12,758 controls, the 677TT genotype carried about 16% higher odds of coronary heart disease. The response is the active B-vitamin forms matched to genotype, rather than the same B-complex for everyone. Klerk et al., JAMA, 2002; Bouzidi et al., Sci Rep, 2020; García-Minguillán et al., Genes Nutr, 2014 (riboflavin status modifies the effect).

Iron: when more is the wrong answer

HFE regulates how much iron you absorb from food, through its control of hepcidin. Overload variants release that brake, so iron accumulates in the liver, heart and pancreas. This is one of the few markers where the recommendation flips completely: if you carry these variants, your formula leaves iron out and the sensible next step is a ferritin test, not a supplement. Feder et al., Nature Genetics, 1996; Adams et al., NEJM, 2005.

Selenium: how much you need to run your defences

GPX1 builds a selenium-dependent enzyme that breaks down hydrogen peroxide and lipid hydroperoxides. The rs1050450 variant changes how efficiently that enzyme responds to the selenium available to it, and the genotype difference shows up most clearly when selenium intake is on the low side. A randomised controlled trial found the rise in glutathione peroxidase activity after selenium supplementation depended on which genotype you carry. Miller et al., Am J Clin Nutr, 2012 (randomised controlled trial); Combs et al., Br J Nutr, 2011; Donadio et al., Clin Nutr, 2018 (SU.BRA.NUT).

Coenzyme Q10: whether you can activate it

Q10 is only useful in its reduced form, ubiquinol. NQO1 performs that conversion. The rs1800566 variant destabilises the protein so it breaks down quickly inside the cell, and homozygous carriers have close to no functional enzyme. Around 9% of people carry the reduced-function version. For them, loading up on standard ubiquinone Q10 is poor value, and the formula routes around it with vitamins C and E, selenium and alpha-lipoic acid instead. Ross et al., Chem Biol Interact, 2000; Fischer et al., BMC Res Notes, 2011 (54 healthy men, ubiquinol 150 mg/day for 14 days); Freriksen et al., J Hum Genet, 2014.

Lactose, and the calcium problem underneath it

This variant decides whether you keep producing lactase into adulthood. The interesting part isn't the intolerance, it's what happens next. People who cut dairy without replacing it commonly end up short on calcium, because dairy was doing most of that work. Your formula adjusts calcium accordingly. Enattah et al., Nature Genetics, 2002.

Omega-3: the variant that reverses the effect

APOA1 builds the main HDL protein. In the Framingham study, women carrying the A allele had roughly 13% higher HDL cholesterol on a high polyunsaturated fat intake, while carriers of the common GG genotype (about two thirds of people) saw little to no HDL benefit from omega-3. In some carriers the response goes the other way and omega-3 lowers HDL. Where that applies, phytosterols do the cholesterol work instead. Ordovas et al., Am J Clin Nutr, 2002 (Framingham Study); de Luis et al., J Diabetes Complications, 2019; Ras et al., Br J Nutr, 2014 (plant sterols meta-analysis).

LDL cholesterol regulation

APOE builds the docking site that lets LDL particles be pulled out of circulation by the liver. APOB is the particle's own recognition protein. SREBF2 acts as the traffic controller for the wider cholesterol-regulation network. Variants across these three change how effectively LDL is cleared from the blood, which shapes how much dietary cholesterol and saturated fat matter for you specifically.

Triglyceride regulation

APOA5 influences how quickly triglycerides are cleared after a meal. Variants here are associated with higher fasting triglycerides and a stronger response to dietary fat and alcohol, which feeds into the fat and omega-3 side of your recommendations.

Your antioxidant defence chain

About 5% of the oxygen your cells take up ends up as superoxide and related reactive species. Clearing it takes a relay: SOD2 turns superoxide into hydrogen peroxide, GPX1 turns that into water, and the glutathione S-transferases mop up the oxidised leftovers. The SOD2 rs4880 variant makes the enzyme harder to import into mitochondria where it's needed. GSTM1 and GSTT1 are commonly deleted outright, meaning no enzyme is produced at all. Weak links in this chain are why two people eating the same diet can hold very different antioxidant reserves. Sutton et al., Pharmacogenetics, 2003; Sørensen et al., Mech Ageing Dev, 2009; Wenzlaff et al., Carcinogenesis, 2004.

Clearing combustion products from grilled and smoked food

Grilling, smoking and charring produce polycyclic aromatic hydrocarbons. Phase I enzymes, CYP1A1 and CYP1B1, chemically activate them first, turning them into reactive intermediates that phase II is then supposed to neutralise. The CYP1B1 Val432 variant can run up to three times faster than the reference version. Fast phase I paired with slow phase II leaves those intermediates hanging around longer. The practical response is gentler cooking plus cruciferous vegetables and their sulforaphane to push phase II along. Wu et al., PLoS One, 2013 (meta-analysis); Lao et al., Lung, 2014; Shi et al., Mol Pharmacol, 2010.

Handling everyday chemical exposure

Glutathione S-transferases tag reactive chemicals with glutathione so they can be excreted. A large share of people carry a complete deletion of GSTM1 or GSTT1, which means that enzyme simply isn't there. Studies across agricultural, industrial and urban groups consistently find null carriers show more exposure-related oxidative stress from pesticides, solvents and particulates. Your formula leans harder on glutathione support and antioxidants when this applies. Ghelli et al., Toxics, 2021; Sun et al., Environ Pollut, 2021; Barrón Cuenca et al., Sci Total Environ, 2019.

Your inflammatory set point

These variants sit in the promoter and receptor regions of the main inflammatory signalling genes, and they change how much cytokine you produce for a given trigger. A joint analysis of 21 studies covering more than 20,000 adults of European ancestry examined the IL6 -174 variant alone. If you carry the higher-output combinations, an anti-inflammatory intake (omega-3, polyphenols, adequate vitamin D, zinc) is a long-term lever worth taking seriously rather than a nice-to-have. Fishman et al., J Clin Invest, 1998; Huth et al., Diabetes, 2006 (21 studies, >20,000 adults); Norde et al., Clin Nutr, 2018 (gene-fatty acid interaction).

Salt sensitivity and blood pressure

AGT sits in the renin-angiotensin system that controls blood pressure and fluid balance. GNB3 affects the cellular signalling behind sodium handling. In a population study using urinary sodium, the slope between systolic blood pressure and sodium intake was about twice as steep in risk-allele carriers as in reference-allele homozygotes. In the DASH trial, genotype groups separated clearly on blood-pressure response to a low-sodium diet. Knowing which group you're in turns "eat less salt" from generic advice into a specific one. Norat et al., Am J Clin Nutr, 2008; Svetkey et al., J Hypertens, 2001 (DASH); Hunt et al., Hypertension, 1998 (TOHP-II).

Caffeine: fast or slow, and why it matters

One liver enzyme handles more than 90% of the caffeine you drink, and this single variant sets its speed. Roughly 41% of people are fast metabolisers, 44% sit in the middle, and 15% are slow. The research is unusually clean here: in slow metabolisers under 59 drinking four or more cups a day, the odds of myocardial infarction were more than doubled, while fast metabolisers showed no such association and in some analyses were protected. Same coffee, different biology. Cornelis et al., JAMA, 2006; Palatini et al., J Hypertens, 2009; Mahdavi et al., JAMA Netw Open, 2023; Sachse et al., Br J Clin Pharmacol, 1999.

Metabolism, bone, connective tissue and vascular genes

Alongside the chapters above, your report genotypes: FTO (rs9939609) and PPARG (rs1801282) for appetite and fat storage, ADRB1 (rs1801253) for adrenergic signalling, TCF7L2 (rs7903146), KCNJ11 (rs5219), HHEX (rs1111875) and HIGD1C (rs12304921) for glucose handling, PON1 (rs662, rs854560) for lipid oxidation, COL1A1 (rs1800012) and ESR1 (rs2234693) for bone and connective tissue, MMP3 for tissue remodelling, HLA-DQA1 (rs2187668) and HLA-DQ8 (rs7454108) for gluten-related risk, ITGB3 (rs5918) and GJA4 (rs1764391) for platelet and vascular function, CFH (rs1061170), ARMS2 (rs10490924) and HTRA1 (rs11200638) for eye health and lutein need, plus two vascular loci at rs8055236 and rs1333049.

These feed the totals for individual nutrients. Vitamin E, for example, is calculated from your Q10 chapter, your oxidative stress chapter and this additional set combined, rather than from one gene in isolation.