Floor first, then the bottle
The biggest vitamin D study ever run failed on both of its main goals
Plate 16
Floor first
Then the bottle
4
Floor compounds
80
Brand partners
Aaron Cuha’s position
This is opinion, not a finding. Everything else on this page is the evidence.
Stop taking supplements just because you are a person. Take them because a number on your blood work is out of range. If you cannot name the blood test number a bottle is changing, you are not on a stack. You are on a guess that happens to come in a bottle.
The reasoning
- Giving supplements to everyone is the thing the big studies keep failing to back up. Vitamin D missed both main goals in a 25,871-person study, and in another it made no difference to deaths (a risk score of 1.04, where 1 means no difference). In both, people already had enough. Giving a nutrient to people who are not short of it has been tested the most and worked the least.
- The exception is the person who is actually low, and you only know that from a blood test. My own blood work is why I take what I take: omega-3 index at 3.9 percent against a target of 8 to 10, vitamin D at 30 against a target of 40 to 60, and ferritin (stored iron) at 435, which is why I take no iron at all.
- A blood test number gives you a rule for stopping. Retest ninety days after starting anything. If the number did not move, stop. Be loyal to the number, not to the bottle. Without a number there is no way to tell a supplement that works from an expensive habit.
- It is cheaper and it is safer. A targeted stack is a handful of things at doses tied to a number, not a cupboard. And every supplement acts like a drug: the dose matters, and too much can hurt. One huge yearly dose of vitamin D raised falls by 15 percent and broken bones by 26 percent in older women.
- There is one thing I will still say is worth taking for nearly everyone, because nearly everyone is short and there is a blood test for it: omega-3. Almost nobody eats enough oily fish to reach a decent omega-3 index. Mine was 3.9 percent against a target of 8 to 10, and you can watch the number move. Even there, know what you are getting. Studies that watch people look strong. Studies that actually gave people omega-3 mostly found no benefit, except for one prescription form. And there is a real risk of irregular heartbeat that grows with the dose.
- I used to put CoQ10 in that sentence too. It does not belong there, and I would rather correct myself in public than keep advice the evidence does not back. The one strong result is in people with moderate to severe heart failure. The most common reason people take it, statin muscle pain, has been tested seven times, and pooled together those studies found nothing. So CoQ10 is a Tier 2 item tied to a diagnosis, not a basic item for everyone, and that is how it is listed below.
Where this goes beyond the evidence
Two places this runs ahead of what has been measured, and they are different sizes. The smaller one is omega-3. Here is the honest state of it. Across 17 studies that followed people, higher blood levels went with living longer. A study giving 1 gram a day to 25,871 ordinary people did not cut heart attacks, strokes or heart deaths. The one study with a strong result used 4 grams of a prescription purified EPA drug, against a dummy pill that is itself disputed. I take it anyway. My reasoning: a shortage you can measure, with a cheap test and a low-risk fix, is worth fixing. That is a judgement, not a study result. The larger one is the whole test-first, then-treat rule, which is my rule, not a study result. Nobody has compared people who take supplements based on blood tests with people on a multivitamin and counted what happened. So I cannot show you a study where my method won. What I can show you is that the other way, giving nutrients to people who are not short of them, has been tested the most and worked the least. Acting on a blood test number is a conclusion I draw from those failures, and you should weigh it as one.
Who this is not for
Anyone using a supplement instead of getting a diagnosis. If a number is out of range, the first question is why. Some answers are illnesses that need treating, not topping up. This also does not apply to supplements a doctor prescribes in pregnancy, gut problems that block absorption, kidney disease or diagnosed shortages. There, the dose is a medical decision, not a personal tweak.
Aaron Cuha, who built this archive, reads the studies behind every page on it, and runs these plans on himself with blood work every three months. He is a coach, not a doctor, and no medical credential is claimed for him anywhere on this site. More about who writes this
What the big studies in people actually found
The biggest vitamin D study ever run missed both of its main goals
Who was studied
25,871 adults in the VITAL study, men aged 50 and over and women 55 and over. By chance, they got 2,000 IU of vitamin D3 a day or a dummy pill, and were followed for about 5.3 years.
It missed both main goals. Vitamin D did not cut cancer, and it did not cut heart attacks, strokes or heart deaths. People on the dummy pill did just as well. At the start, people averaged 30.8 ng/mL of vitamin D, which is already enough. Only 12.7% were below 20.
Study in peopleVitamin D supplements and prevention of cancer and cardiovascular disease (2019)What this does not show
That vitamin D is useless, or that topping up does not matter for someone who is truly low. It shows that giving 2,000 IU to people who mostly already have enough does not prevent cancer or heart disease. The often quoted 22% drop in diseases where the body attacks itself was a side result. It was borderline to begin with, and it faded to maybe no effect once two more years of cases were checked. It also did not last after people stopped.
And the biggest vitamin D study on death found no difference
Who was studied
The D-Health study. Older Australian adults got a high dose of vitamin D once a month or a dummy pill. The main thing measured was death from any cause.
Nobody lived longer on vitamin D (a risk score of 1.04, where 1 means no difference). The dummy pill group already averaged about 31 ng/mL. That is the same problem VITAL had: you cannot show the benefit of topping people up when they are already full.
Study in peopleThe D-Health trial: a randomised controlled trial of the effect of vitamin D on mortality (2022)What this does not show
Anything about people who are truly low. That was tested separately, in 8,851 children in Mongolia, 95.6% of whom were low. Vitamin D tripled their blood levels, and it still did not help the main thing measured. That is the most awkward result in this research.
Big vitamin D doses taken once in a while led to more falls and broken bones
Who was studied
2,256 women aged 70 and over living at home. By chance, they got one 500,000 IU dose of vitamin D by mouth each year, or a dummy pill.
The vitamin D group fell more, not less. The rate of falls was 1.15 times higher and broken bones 1.26 times higher. More is not safer. In this study, more was worse.
Study in peopleAnnual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial (2010)What this does not show
That normal daily doses carry the same risk. This was one huge dose a year. The harm has shown up in other studies of big doses taken once in a while too, so it does not rest on one study. It is the clearest proof in the field that a supplement acts like a drug: the dose matters, and too much can hurt.
Two big omega-3 studies, opposite results, and the difference may be the dummy pill
Who was studied
REDUCE-IT gave 8,179 people on statins with high triglycerides (a blood fat) either 4 g a day of icosapent ethyl, a prescription fish oil drug, or a dummy pill made of mineral oil. STRENGTH gave similar people a different high-dose omega-3, or a dummy pill made of corn oil.
REDUCE-IT strongly cut heart attacks, strokes and heart deaths. In STRENGTH, people on the dummy pill did just as well. These two are the most argued-over pair in supplement research. The main explanation is not the drug. In REDUCE-IT, the mineral oil dummy pill went with rises in inflammation and LDL in the dummy group. That would widen the gap between the groups without the real drug doing any more.
Study in peopleEffect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk (STRENGTH) (2020)What this does not show
That REDUCE-IT is wrong, or that the mineral oil question is settled. The defence of that dummy pill was published in a journal section the drug maker paid for. One author worked for the drug maker, and the lead author chaired the drug maker's safety data committee. That is worth knowing when you weigh it. What the pair does show is that a high-dose prescription EPA drug is not the same thing as a fish oil capsule. Neither result carries over to the other.
Omega-3 raises the risk of an irregular heartbeat, and the risk grows with the dose
Who was studied
VITAL-RHYTHM, a planned check for irregular heartbeat (atrial fibrillation) inside the 25,871-person VITAL study
People taking omega-3 were more likely to develop an irregular heartbeat (atrial fibrillation). Across the wider research, the risk grows with each extra gram a day.
Study in peopleEffect of marine omega-3 fatty acid and vitamin D supplementation on incident atrial fibrillation (2021)What this does not show
That omega-3 does more harm than good overall, or that the small amount in food carries the same risk. It does mean the common belief that fish oil has no downside is wrong. Someone already prone to an irregular heartbeat has a clear reason to talk about the dose with a doctor, not keep raising it.
Studies that just watched people promised a lot, which is exactly why testing matters
Who was studied
A review that pooled 17 studies that followed people over time, looking at blood omega-3 levels and death. And a separate large pooled review of vitamin D levels and death.
People with the highest blood omega-3 levels had about a 15 to 18% lower death rate than those with the lowest. People in the bottom quarter for vitamin D died at a much higher rate than the top quarter. Both links are big, steady, and show up again and again.
Study in peopleBlood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies (2021)What this does not show
Cause. Low vitamin D is a sign of being indoors, being unwell, sitting a lot and carrying more weight. Each of those raises the death rate on its own. That is the whole lesson of this section. For these two nutrients, the link in studies that only watch people was as strong as those links get. And when people were actually given them, most studies still found no benefit.
CoQ10 cut heart problems in heart failure and did nothing for statin muscle pain
Who was studied
In Q-SYMBIO, 420 people with moderate to severe long-term heart failure got CoQ10 100 mg three times a day or a dummy pill for two years. Separately, 7 studies in 321 people tested CoQ10 for muscle pain from statins.
In heart failure the result was strong. Major heart problems hit 15% of people on CoQ10, against 26% on the dummy pill. Deaths from heart disease were 9% against 16%, and deaths from any cause 10% against 18%. For statin muscle pain, people on the dummy pill did just as well when the studies were pooled. It did not help people stay on their statin either.
Study in peopleThe effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO, a randomized double-blind trial (2014)What this does not show
That CoQ10 helps healthy people. Q-SYMBIO was 420 people with diagnosed moderate to severe heart failure, already on standard treatment. Its short-term checks at 16 weeks showed nothing, before the two-year result came in. No study has tested CoQ10 in healthy adults taking it to live longer. And the most common reason people take it, statin muscle pain, is the one thing it has been shown not to fix.
The statin muscle pain result, on its own, because it is why most people take it
Who was studied
A review that pooled 7 studies against a dummy pill, in 321 people with muscle pain from statins
No help for muscle pain. People on the dummy pill did just as well. No more people stayed on their statin either. Only 2 of the 8 studies looked at showed a benefit on their own.
Review of studiesEffect of coenzyme Q10 on statin-associated myalgia and adherence to statin therapy: a systematic review and meta-analysis (2020)What this does not show
That nobody is helped. Pooling studies that found nothing can hide the few people who do respond, and the studies were small, from 37 to 76 people each. What it does mean: if you take CoQ10 for statin muscle pain, you are acting on an idea that has been tested seven times and has not held up.
The method, in 5 steps
The order is the part people get wrong. They buy first and never test. That makes it impossible to know if anything is doing anything.
- 01
Get blood work before you buy anything
A starting set of tests: a full cholesterol panel with particle size, HbA1c and fasting insulin, high-sensitivity CRP, ferritin and a full iron panel, 25-hydroxy vitamin D, an omega-3 index, homocysteine, liver enzymes, and thyroid tests. Without this you cannot tell a supplement that works from an expensive habit. You also cannot tell a helpful one from a harmful one, as the iron entry above shows.
- 02
Start the basics, then wait
Tier 1 goes in first, on its own. Add eleven things in one week, and if something helps or upsets your stomach, you will never know which one it was.
- 03
Add something only for a blood test number that is out of range
One item per number, and write the number down next to it. If you cannot finish the sentence 'I am taking this because my ______ is ______', the bottle does not go on the list.
- 04
Retest at ninety days and be loyal to the number, not the bottle
If the number moved, keep going. If it did not, stop, and do not assume the dose was too low. A supplement that has had ninety days and has not moved the one number it was chosen for has told you what it does.
- 05
Re-examine the whole list twice a year
Blood test numbers change, and the reason you started something can go away. A stack should get smaller over time at least as often as it gets bigger.
The owner’s own stack, with the blood marker beside each item
This is one person’s routine, built from one person’s blood test. We publish it so you can see the rule in use, not just described. It is not advice for you, and the doses are tied to his numbers. The column that matters is the blood marker. If an item cannot name one, we say so.
The floor, for almost everyone
Four things, about sixty dollars a month from good quality brands. These are the ones the owner takes without waiting for blood work. His reasoning: almost nobody eats enough oily fish, almost nobody gets enough sun, and creatine is the most studied supplement there is. Even here, get the starting blood work. Three of the four have a number you can read, and the number tells you whether the dose is right.
- The blood marker
- Omega-3 index, target 8 to 10 percent
- What the studies show
- Studies that watched people strongly link blood levels to living longer. Studies that gave people omega-3 mostly found no benefit, except for one high-dose prescription form. There is a real risk of irregular heartbeat that grows with the dose.
- The blood marker
- 25-hydroxy vitamin D, target 40 to 60 ng/mL
- What the studies show
- Two very large studies found no benefit for cancer, heart attacks and strokes, or death, in people who already had enough. Topping up someone who is truly low is a different question, and it is the only one this dose is aimed at.
- The blood marker
- Red blood cell magnesium, not serum magnesium
- What the studies show
- Serum magnesium is a poor test, because the body holds the blood level steady by pulling from its stores. The sleep and thinking claims are thin, and the most quoted brain magnesium paper was pulled by its own authors.
- The blood marker
- None. This one is not marker-driven.
- What the studies show
- The most studied supplement there is. Many studies in people show gains in strength and lean mass, and its safety record is unusually clean. Take it whether or not you lift.
Tied to a number on your panel
Nothing in this tier goes in until a specific blood test number says so. Each one comes back out if the number has not moved in ninety days. This is where most people's cupboards should shrink. Every item below names what triggers it.
- The blood marker
- Added when LDL particles are small and dense, called pattern B
- What the studies show
- Studies in people exist and show changes in cholesterol numbers. They are small, mostly from one research group in Italy, and measure blood fats, not heart attacks or strokes.
- The blood marker
- Added when HbA1c or fasting blood sugar is high
- What the studies show
- Several studies against a dummy pill and against metformin show effects on blood sugar and blood fats. Study quality is mixed, most are small and from one region, and none measured real health events.
- The blood marker
- Added when high-sensitivity CRP is up
- What the studies show
- Getting it absorbed is the whole problem. Plain turmeric powder is not the same thing as a phytosome form or a form with black pepper extract (piperine). Studies use specific forms, and results from one do not carry over to another.
- The blood marker
- Added when liver enzymes are raised
- What the studies show
- Proven as a prescription drug for paracetamol (Tylenol) overdose and for thinning mucus. Using it for long life or general liver support is a stretch from that, not the same evidence.
- The blood marker
- Added only with an MTHFR gene variant, and adjusted on homocysteine at retest
- What the studies show
- B vitamins reliably lower homocysteine. Whether lowering it changes what happens to people is the part large studies have failed to show, again and again.
- The blood marker
- Added when there is a diagnosis of moderate to severe heart failure, under the care of the doctor treating it. Not added for statin muscle pain.
- What the studies show
- The one strong result on real health events in this group, and it is narrow. Q-SYMBIO gave CoQ10 or a dummy pill to 420 people with moderate to severe heart failure on standard treatment. Major heart problems dropped from 26 percent to 15 percent over two years. Its own sixteen-week checks showed nothing first. For statin muscle pain, seven studies in 321 people, pooled, found no benefit and no help staying on the statin.
- The blood marker
- Excluded because ferritin (stored iron) is high. The owner's is 435.
- What the studies show
- This is the most important entry in the tier. It is the one where the default habit of taking a general multivitamin actually causes harm. High ferritin does not need help. Get the blood test before you ever take iron.
Optional, and honestly optional
These are the ones the owner takes and would drop first. They are labelled for what they are, not promoted. A plan that cannot say which parts are guesses is not a plan.
- The blood marker
- None. Taken for stress and sleep.
- What the studies show
- The product matters more than the herb here. Studies use a standardised root extract. In one check of 25 store products, only two were confirmed to be made from the root.
- The blood marker
- Alongside glucose markers
- What the studies show
- The best evidence is for nerve damage from diabetes, at doses and in people unlike most users.
- The blood marker
- Alongside LDL
- What the studies show
- They reliably lower LDL a little. No study has shown that lowering it this way prevents heart attacks or strokes.
- The blood marker
- None. Taken for prostate health.
- What the studies show
- Studies that watched people link it to prostate health. Studies that gave people lycopene are few and do not agree.
- The blood marker
- Alongside glucose markers
- What the studies show
- Small blood sugar effects in small studies, and reviews that pooled them disagree. Truly optional.
Going deeper: blood markers, what-to-do-when guides, and the 24 supplements
The method above now runs through the site. Each of these supplement pages has four extra sections: when it earns a spot, which blood tests belong beside it, how a coach reads the number, and what people usually order. The ranges are for learning only. Aaron is a coach, not a doctor.
Blood markers
What to do when
The rest of this pillar
open nowBlood test partners, and the panel that comes first
The test-then-treat rule needs a place to order your blood test. US blood test partners a coach can work with are on /bloodwork/partners. Labs that test peptide vials are on /prices/labs. What each blood marker means is on /markers.
Open open nowWhat is actually in the bottle
The most-quoted number in this field was pulled because the data was made up. Two products sold as NMN had no NMN in them. Only two of twenty-five ashwagandha products were made from the plant part the studies used. Plus what each quality seal does and does not check. It is not what people think.
Open open nowSupplement partners, how we rate them
Brands a coach can work with, graded on a public scorecard for quality and honest claims. Top-grade Tier A cards, the full A to D table, and multi-level marketing (MLM) names kept on the page as warnings, not promotions. We are not paid unless a card shows a rate.
OpenCreatine
The most studied supplement there is, and the one entry on the floor list that needs no blood test. What it does beyond strength.
Open open nowNAD precursors
NMN and nicotinamide riboside, what the studies in people measured, and why product testing matters more here than almost anywhere.
OpenQuestions people ask about this
- Does vitamin D actually do anything?
- For people who are not low, the big studies say no. It did not prevent cancer, heart disease or death. A study of 25,871 people failed on both of its main goals. A separate study on deaths gave a risk score of 1.04, where 1.0 means no difference. Both studies mostly took people who already had enough vitamin D, and that mistake keeps repeating. Whether topping up helps someone who is truly low is a separate question. The study support for that is much weaker than most people assume.
- Which supplements are worth taking without a blood test?
- Creatine has the biggest and cleanest set of studies in people of anything in this group, and it does not depend on a blood marker. Omega-3 and vitamin D are on the owner's list because almost nobody eats enough oily fish or gets enough sun. But both have a blood marker you can read, so a test turns a guess into a measurement. Everything else should wait for your blood test.
- How do I know if a supplement is working?
- Name the marker before you start, then retest it at ninety days. If the number did not move, stop. This is the single practical rule on this page, and it is what separates a stack from a cupboard. Be loyal to the marker, not the bottle.
- Is 59 percent of herbal supplements mislabelled?
- No. That number comes from a 2013 paper. The paper was pulled in July 2024 after an investigation by the authors' own institution found signs the data was made up. Label problems are real, and other groups have found them in other ways. But nobody has, or can have, one mislabeling rate for the whole market. Sellers do not have to list their products anywhere, so nobody knows the total to count against.
- Does CoQ10 help with statin muscle pain?
- A review that pooled seven studies in 321 patients says no. Pain scores barely moved, an average change of minus 0.42, and the true effect could easily have been zero. It did not help people stay on their statin either. CoQ10 does have one strong result on real health outcomes, but it is in people with moderate to severe heart failure. That is not healthy people, and it is not statin muscle pain.