Over the years I have occasionally had good success for depression with fish oil, NAC, inositol, L-methylfolate, very low dose lithium (150mg). I have not used a probiotic long enough to have seen obvious success. In a discussion on CUPP, others had a similar experience with inositol as I have had, finding it unimpressive.  However, when I looked at a list I keep, I found that seven people had excellent benefit for depression and/or anxiety from inositol.   Most of them took it for years. I have one fellow who weighs  ~350 pounds and who is highly resistant to trying things.  Every time he took inositol he felt immediately better, so has now been taking it steadily for a few years.  Perhaps I am not trying inositol enough and maybe I should be using higher doses than 30 grams per day. I have a  bipolar schizoaffective patient who absolutely needs 18 pills of fish oil, which he has taken since the first paper in 1999.  When we try to reduce to 10 pills he immediately slides into an unpleasant mild to moderate depression, which remits within days of going back 18 pills. Fortunately, he has no problem at all taking 18 pills. I usually push people to take 6 to 10 pills.  Are there many other people who would have responded if I had inveigled them to try 18 pills?

It is difficult to induce people to try these nutraceuticals.  And the benefit can be difficult to evaluate, especially if it occurs slowly.     If the patient is in rough shape, usually he/she wants the medication increased, changed or something added.   They don’t want to try something that sounds weak and faddish.   If I do both the medication and the nutraceutical at the same time, I eventually either stop the nutraceutical abruptly or lower the medication very slowly—to discover what is necessary.

I sometimes try to induce people to try a very high dose of four proven supplements, all at once, for a month.   It is a major project they can focus on.   My guess is that there is only a 20% chance with each agent of dramatic benefit.   It makes it much more appealing if we try 4 things at once, as the odds of benefit would be significantly better.  If there is good benefit, we can slowly stop one at a time, to find out what is necessary.

When nutritional things work, I rarely find them to poop out—which is different from medications, especially in some bipolar people.

Instructions to patient:   This is a list of nutritional things I put together. When you have a depression again, maybe we should do four or even six things: NAC, inositol, probiotic, L-methylfolate/5-MTHF, fish oil, and low dose lithium —all together in high doses for a trial of 6 to 8 weeks.  Double blind studies have proven each of them can help depression.  If you have obvious benefit, later on we can sort out what one helped.   It may be easier to do this as a project of all at once.   If we tried each one by itself for 6 weeks, that would take 30 weeks—which can be daunting and discouraging.

Usually, I do one at a time—or two at a time, especially if one is lithium 150mg.  We can do it the way you prefer.


  • 6-10 fish oil pills per day; or even, for a week, try 18 pills/day—I have one man who has been on 18 pills since 1999; he is mildly depressed if we reduce it. If you eat a big salmon steak or tuna steak, it’s like taking 45 pills. It is just inconvenient to eat that much fish and is only the fish fat that has an antidepressant effect, so the pills are much more convenient. If you spread the pills to five pills twice a day or five pills three times a day it makes it much easier psychologically to take that many pills.  If you use Omega via, then 10-12 pills are probably enough.  Omega via is a small 500mg/pill with 500mg of EPA in it, so 3 to 4 pills may be enough for depression   It is a smaller capsule, but with more EPA—the only fat that helps depression.
  • NAC (N-acetyl cysteine)  4 grams per day.  4 grams  –e.g., 7 pills of 600mg.  It turns out pills work better than powder, as the powder is oxidized by air.
  • inositol, aim for 20mg grams /d = about 3 teaspoons twice a day, then slowly increase to 20 grams a day which is equal to 10 g twice a day= about three rounded teaspoons twice a day, or more
  • probiotic: one or two pills per day; alternate 3 or 4 brands. This occasionally helps depression.   g., there is a randomized controlled study showing that taking a probiotic after a manic episode greatly reduces the risk of depression and mixed states.   A probiotic may help depressions in general by increasing the good bacteria in the intestine.    Bacteria release chemicals that easily pass from the colon to the bloodstream, then to the brain, where they affect how we feel.  Some brands of probiotic have nothing in them since they are not FDA regulated.  Buy 3 or more brands and alternate them. Yogurt also helps, especially if it has acidophilus.
  • L-methylfolate/5-MTHF / Deplin 15mg/day –the active folate vitamin. Folic acid is not found in our body or in food.  It is cheap to make and the vitamin companies know that most of us can convert it to the active vitamin: L-methylfolate.
  • lithium 150mg: one per day— I call this nutritional because it is such a low dose of a mineral–a basic element. Blood monitoring at this dose is not necessary.  Side effects are usually non-existent.  In areas of the world where there is a lot of lithium in the drinking water, there are better health outcomes, especially less Alzheimer’s and fewer suicides.   As of 8/2019,  over a 4 year period,  62 of my patients had a significant and durable antidepressant effect in ≤ 2 weeks.   In others, it may help as the month’s pass.  There is strong evidence it prevents cognitive decline as well as Alzheimer’s.   It is the only substance that increases the grey matter of the brain—i.e., the thinking areas.    Everyone with depression should be on at least 150mg/day, I believe—unless they have kidney disease.  With people over 75, I have seen an antidepressant effect at even 40mg per day. In one instance, there was significant benefit on 150mg once a week—the dose later needed to be increased to 150mg every other day.


  • Cytomel (liothyronine/T3) –one of our own thyroid hormones.
  • SAM-E 400mg twice a day –  a substance we also make ourselves.  It works better with B12 and folate
  • Vitamin D ~4000 I.U. to 10,000 I.U. / daya steroid hormone. Everyone is low in it because one step in manufacturing it requires exposure of our skin to UVB light from the sun.   An expansive area of skin must be exposed when the sun is over 45 degrees above the horizon.      Humans have been around 2.5 million years, and farming ≤ 12,000 years.   If we were hunter gathers for 4 hours, then we have been horticulturists only one second. The choice of clothing for hunter gatherers was:  fur, leather, or weave something from plants.  Probably we did not wear very much when it was warm and we were outside all day, making ~10K I.U.’s per day.
  • Curcumin: in one study 1000mg helped Atypical Depression, not melancholic depression. 1000mg seems to me a low dose.


  • EXERCISE: ONE HOUR OF VIGOROUS EXERCISE 5 DAYS PER WEEKif it is just walking, maybe you should double that.
  • DIET: THE BEST DIET FOR DEPRESSION IS Mediterranean Diet OR VEGAN DIET, which are similar: [they may work because it is an anti-inflammatory diet]

no carbohydratesincluding no evil white things:  no sugar, potatoes, bread, rice or pasta;  and, of course, no cookies, cake or ice cream.

no meat except fish; no animal products at all (no cheese, milk,  or eggs)

these are ok: vegetables, salad, nuts, berries, fruit, olive oil; you can put flax seed oil [an omega 3, good for the heart] in your salad dressing or just use olive oil [extra virgin olive oil has been proven better for the heart than regular olive oil]

  • SIGNIFICANT WEIGHT LOSS REDUCES DEPRESSION —–e.g., a young woman [BP II] in her late 30’s who I have treated for ~20 years. When she went to ~130 lbs and stayed there –instead of ~165 lbs–her severe depressions stopped. It was vastly easier to keep her euthymic, though she still needed medication.  She lost the weight by assiduous exercise and dieting–not easy, but doable. 

NOISE: always have music or TV on