The saddest day of the year is supposed to be “Blue Monday". This year, Blue Monday is January 15. That is why I am uploading this article on depression today. I’m not sure if there is any merit to the Blue Monday theory, but I certainly feel that mid-January is a depressing time of year, especially the more north you go.
There are many things someone can utilize to help improve their mood, lessen their irritability and aggression, improve behaviour (for children), and reduce melancholy. Also, of utmost importance, there are a plethora of substances that can help prevent suicide.
Some current articles that I’ve written that are related to mood:
Addictions and Substance Abuse
Soon, I will release articles related to psychiatric (Eating disorders, PTSD, Schizophrenia, and more on Bipolar Depression), behavioural (ODD) and neurodevelopmental disorders (ASD).
If you want to be notified when new articles are released, consider subscribing, it is free to do so.
Suicidal ideation is one of the most significant symptoms of depression that should be ameliorated, and thankfully there are a plethora of substances that have been shown to lessen suicidal thoughts and improve depression and bipolar symptoms.
The various physiological causes of depression are not necessarily that different than some of the causes of anxiety. Depression can involve high glutamate and low GABA, it can certainly be influenced by high levels of stress hormones, particularly cortisol, and it can be exacerbated by low levels of anti-stress hormones such as pregnenolone, progesterone, DHEA, and allopregnanolone. As such, increasing the production of beneficial hormones, or supplementing with them, such as pregnenolone can improve mood disorders, such as bipolar disorder.
For example, things that improve the glutamate-to-GABA ratio can help with a wide variety of conditions, including depression. As I’ve mentioned in practically every article thus far, vitamin B6 and magnesium are very effective at balancing out glutamate and GABA. For instance, vitamin B6 is needed to convert glutamate into GABA. Remember, glutamate is pro-anxiety (and can be high in depression) whereas GABA is very calming, and is anti-depressive. A depressed person would likely benefit from higher GABA, in relation to glutamate. The amino acid agmatine can also balance glutamate and GABA, and agmatine has been shown to amplify the anti-depressive effects of lithium.
Many people use OTC lithium, such as lithium orotate, effectively to reduce their depression (and bipolar depression) symptoms. Lithium has many mechanisms of action, but one thing it does is it lowers ammonia. High ammonia is very harmful and is involved in essentially every mood disorder, including depression. Lithium does many other things, such as improving the utilization of vitamin B12. It can also lower various stress hormones, and it can increase BDNF (similar to magnesium) which is helpful for depression. Ceylon cinnamon can also lower ammonia. Lithium also seems to be able to help normalize glutamate. It has the ability to enhance dopamine production via increasing its synthesis from tyrosine hydroxylase which is very important when it comes to anhedonia, or lack of feeling and motivation, often seen in depression.
Lithium orotate has also been shown by Dr. James Greenblatt to be useful for Disruptive mood dysregulation disorder (DMDD)
Lithium combined with agmatine seems to be very beneficial for depression. Both of these substances alone seem to be very beneficial for mood in general but the combination may be a better option for those who are really struggling. Lithium is also seemingly very useful when it comes to suicide prevention. Lithium and agmatine are also able to help curb addictions and withdrawals, and this is very important as addictions have a great potential for leading to depression and related maladies. (find out more about addictions and substance abuse in my article on the topic). To find out more great information about the use of over-the-counter lithium orotate, consider reading the book “Nutritional Lithium, a Cinderella Story” by Dr. Greenblatt.
Deficiencies in molybdenum and manganese can make someone more sensitive to glutamate (and sulphites), so consuming enough of these minerals is very important. Mussels, maple syrup, pineapple and legumes are very good sources of manganese, molybdenum is high in liver, legumes (like peas) and gluten-free oats. Supplementation with these minerals may be warranted.
There are many other things that can increase GABA, which would likely improve mood drastically. Lemon balm, chamomile and valerian root are some options, that can either be consumed via a tea, tincture or as a supplement. Taurine, glycine and theanine are three amino acids that can really help with depression, partly by their pro-GABA effects. Glycine seems to be particularly helpful, and it also helps with sleep and can reduce the startle response.
Increasing dopamine may be very helpful for certain depressions, as dopamine is important for motivation and feeling good. Not to beat a dead horse, but vitamin B6 is a very potent prolactin-lowering vitamin, and prolactin is a major inhibitor of dopamine. Things that lower prolactin almost always improve dopamine levels. Vitamin B6 thus can be a potent antidepressant as it helps balance glutamate and GABA, and prolactin and dopamine. Zinc and vitamin E can also lower prolactin. In addition to lowering prolactin, zinc can help to lower excess glutamate, as can magnesium. Some people suggest supplementing tyrosine (or phenylalanine) to improve dopamine levels, and this may work, but there is also the potential that tyrosine would increase stress hormones like adrenaline.
High-stress hormones, especially cortisol, can drastically worsen depression. As I’ve mentioned in many past articles, a major cause of chronically elevated stress hormones would be the suboptimal functioning of the thyroid, liver and gonads (ovaries or testicles). When these three are not working optimally, the body compensates with higher levels of pituitary and adrenal hormones. This leads to chronically elevated adrenaline, aldosterone, cortisol, prolactin and many other stress hormones. So the best long-term approach would be to lower the excessive pituitary and adrenal hormones by increasing the function of the thyroid, liver and gonads. Other things that can help acutely lower stress hormones could be certain herbs, such as ashwagandha. Supplemental pregnenolone and DHEA seem to be very useful in protecting against excess cortisol, and so can progesterone. I discuss this in great detail in my article on PCOS.
“So, when I saw bulging veins disappear a few minutes after women took progesterone, along with a sudden lifting of extreme depression, I guessed that their circulation had become more efficient, and that better oxygenation had changed their mood.
Several types of mental problems are associated with edema of the brain-an excess of water, or the presence of water that is functionally abnormal, less constrained, as measured by MRI. MRI can also directly measure the redox balance, NAD/NADH, of the brain, and it has been found that schizophrenics and manic depressives have lower ratios, that is, their cells are less well oxidized. Before any mental impairment develops, people who later develop Alzheimer's disease, experience reductive stress (Lloret, et al., 2016). “
- Ray Peat, Ph.D.
Speaking of hormones, there are many anti-stress and thus anti-depressive hormones and therefore increasing the production of these hormones would be highly therapeutic for depression. Increasing thyroid function and consuming more nutrients like vitamins A and B5 can help your body convert cholesterol into more pregnenolone. Pregnenolone can then become the other hormones, like allopregnanolone. The overall effect would then be the improvement of depression. Allopregnanolone also seems to be useful for post-partum depression. Since allopregnanolone is a downstream metabolite of both pregnenolone and progesterone, it appears that progesterone (or pregnenolone) deficiency can lead to an allopregnanolone deficiency, making post-partum depression more likely.
The author of the book “Nutrient Power”, William Walsh PhD, has said that copper overload could be a contributor to postpartum depression. One offered solution to deal with copper excess is to consume more zinc (via food or supplementation), and possibly using the amino acid histidine. Other orthomolecular doctors like Dr. Carl Pfeiffer have suggested also utilizing manganese and niacinamide.
Something really important to consider in depression is that low energy production can drastically worsen mood. Increasing energy, ATP production, can be very beneficial for depression. This may be one of the mechanisms by which creatine has been shown to improve depression.
Remember, around half of methylation goes towards creating creatine, so some suggest supplemental creatine to help lessen the stress on the methylation system (for those who have methylation issues). This may also be a viable mechaisim for how creatine helps alliviate depression symptoms.
Certain B vitamins and minerals like magnesium can all increase someone’s ability to produce energy. B1, B2, B3 and B5 are probably the most important B vitamins when it comes to energy production, but they are all important to some degree. Good thyroid function is essential for optimal energy production, so improving the metabolic rate will likely be very effective in not only increasing physical energy but also improving depression. Using glucose well is imperative for optimal energy production, especially in the brain. Furthermore, using glucose well helps to prevent a high ammonia state, and as mentioned earlier, high levels of ammonia can contribute to mood disturbances. I’ve written an article on how to utilize glucose well that is informative.
“Hypothyroid people, with low production of CO2, are very susceptible to stress-induced hyperventilation, and they are often in a state of physiological hyperventilation. They are susceptible to over-production of ammonia (De Nardo, et al., 1999; Marti, et al., 1988) and lactate (Zarzeczny, et al., 1996), and to psychosis, especially depression and mania.
“Thyroid… has been commonly used in the treatment of depression, and there are many indications that, as it relieves the depression, it is also correcting a state of stress, lowering the cortisol which is typically chronically increased in depression, and making sleep restful, rather than debilitating.”
-Ray Peat, Ph.D.
Another important consideration for optimal energy production is having enough NAD. This is likely part of the reason why supplemental niacinamide can help with depression and mood. Niacinamide can help increase NAD via multiple mechanisms, one of which is that it can act as a precursor to NAD. Oxidizing agents and quinones are also able to help improve NAD levels. Some examples of these quinones would be COQ10 (Ubiquinone), Vitamin K2 (Menaquinone) and Thymoquinone found in Black Seed/Nigella Sativa. Methylene Blue (“MB”) is also able to increase NAD and Ray Peat Ph.D. once mentioned that 0.5mg of MB (typically one drop of commercially available products - links at the end of the article) can help with depression.
Low cholesterol is observed to be a risk factor when it comes to suicide. I believe the reason for this is because cholesterol is the basic building block of the steroid hormones, so when cholesterol is low the body has less ability to make the steroids. Many steroids, like pregnenolone, progesterone and allopregenenolone seem to be anti-depressants and seem to be able to help prevent suicide. So, it makes sense that low cholesterol, leading to low hormone levels, can increase one’s chances of depression and suicide. A quick solution here would be to supplement with some of these hormones, such as pregnenolone as it’s the first hormone produced from cholesterol. Some reasons someone could have very dangerously low cholesterol is if they are on a cholesterol-lowering drug or if their liver is not functioning optimally. I think going on a statin is a terrible idea, especially for those with depression or a neurodegenerative disease. High cholesterol is often a result of poor thyroid function, as the active thyroid hormone, T3, is needed to convert cholesterol into steroid hormones. Find out more about this in my article on high blood pressure and high cholesterol.
Pregnenolone would be the go-to hormone to supplement as it’s inexpensive, highly beneficial and over-the-counter, plus men and women can use it with ease. (Pregenenolone products are linked at the end of the article). Pregnenolone is the first hormone to come after cholesterol and it has the ability to be converted downstream into all the other hormones, as needed. However, pregnenolone itself has many important functions, especially when it comes to the brain. Pregnenolone would thus be a great thing to supplement with if someone is depressed or is suffering from suicidal thoughts. The long-term solution would be to increase cholesterol production from the liver so that the body can actually make its own pregnenolone. Eating enough food, especially saturated fats and carbohydrates is important for the body to produce enough cholesterol. Vegans are often at risk of low cholesterol, also people who undereat may be at risk of having low cholesterol levels. One last note on cholesterol, higher cholesterol seems to be protective against dementia in old age. If you want to protect against dementia, a statin drug may be one of the worst things you can do.
Oxaloacetate supplementation has been shown to be very effective for mood-related symptoms of PMS, including suicidal ideation. It seems reasonable to predict that increasing oxaloacetate should help lessen those symptoms in general, and not just as a result of PMS. Oxaloacetate is created in the body by the enzyme pyruvate carboxylase, and this enzyme requires enough biotin and manganese. Thus, it is important to consume enough of those nutrients or to supplement if warranted. Or, you can also supplement oxaloacetate directly, the product is called benaGene.
Vitamin D and bright light have time after time been shown to be useful for depression. So it would make a lot of sense for someone to try and get enough bright light exposure, especially morning and evening sun, and to make sure their vitamin D levels were adequate. Testing vitamin D on a blood test is a great idea, and if it is low then do what you can to increase it, and this can include supplementing vitamin D. Also, low vitamin D will increase PTH (parathyroid hormone) and high PTH is involved in bipolar depression. Vitamin D also seems to be able to help with suicide prevention.
Improving gut health and gut motility is essential for protecting against depression as any time there is intestinal inflammation and irritation the mood will worsen, especially if any of the “toll-like receptors”, such as TLR4, are activated. Gluten and A1 cow dairy protein can cause serious intestinal inflammation and can thus worsen mood. Anything that causes gas, like a lot of raw vegetable consumption or beans, can also worsen mood. Things that can help clear up the intestines would be a daily raw carrot salad (shredded raw carrots, olive/coconut oil, salt, vinegar), boiled white button mushrooms, aloe vera and Cascara Sagrada (as a safe laxative if needed). Some people may need to use some antimicrobials such as a spore-based probiotic (such as CoreBiotic), oregano oil, monolaurin etc. Some things that can help prevent leaky gut are 5g a day of creatine monohydrate and zinc carnosine.
Sleep is important, that’s obvious, but I truly think it is important for people to try and wake up early, at around the same time every day. I think waking up later in the day is a recipe for depression and an overall lower mood for many reasons. We should attempt to be “up and at’em” while the sun is up. Sleeping in here and there when you need to catch up on sleep is certainly fine, but making an effort to be awake early in the morning does seem to be very important. Interestingly, many depressed people can’t seem to wake up early in the morning and get going with the day, and severely depressed people often sleep for many hours during the day. Find out more about Insomnia in my article on the topic.
Negative ions are also supposedly very helpful for depression. Natural sources of negative ions are waves, rain, and trees, so generally being in nature is good for depression, in part due to the negative ions. Rushing water in general produced negative ions and this is probably part of why people feel better when taking long showers. It is also possible to purchase a negative ion generator. Apparently, beeswax candles can also emit/release negative ions, but this isn’t confirmed. Some also say that the orange Himalayan salt lamps emit negative ions.
When it comes to severe depression where people believe they need to be medicated, it’s important to understand that many of the “first line” medications used for depression, namely SSRIs, can be extremely harmful and often don’t really work that well. In fact, depression’s worst symptom is arguably suicide and suicidal thoughts, and SRRIs are shown to increase the risk of suicidal ideation. Furthermore, the “most effective” SSRIs are thought, by some, to work because they increase allopregnenolone levels in the brain, and not because of the serotonin reuptake inhibition. In other words, even when SSRIs “work” they are likely working as a result of mechanisms different than their reported main mechanisms of action.
Other medications that are much safer (and probably way more effective) should be tried first. Medications like clonidine, which can help with depression especially if it’s combined with anxiety, or amantadine and memantine can be very helpful. Many people know about ketamine therapy for depression, and ketamine is a strong NMDA blocker. Amantadine and memantine are both weak NMDA blockers, with very minimal side effects but have the potential to be very helpful for depression. So, if you feel you need to be medicated, please talk to your doctor about these safer options. If you must go on an antidepressant, the older tricyclic antidepressants seem safer than SSRIs in my opinion, but they are certainly not perfect. Also, the anti-serotonin, anti-prolactin and pro-dopamine medication bromocriptine has shown promise for the treatment of depression. Bromocriptine is an “ergot derivative” and as such other ergot derivatives may be useful for the treatment of depression.
Amantadine in Treatment of Dysthymia—The Pilot Case Series Study
Possible Antidepressant Effects of Memantine—Systematic Review with a Case Study
Bromocriptine treatment of depressive disorders. Clinical and biochemical effects
Quick summary list of some things that can help with depression, mood disorders and suicide prevention:
Vitamin D AND Bright light
Oxaloacetate (benaGene)
Also supplementing biotin and manganese as both are needed to produce oxaloacetate naturally.
Lithium & Agmatine.
Lithium orotate is very helpful for mood issues and depression, especially manic depression - but severe bipolar depression might respond better to lithium carbonate). The general recommendation for lithium orotate is 5-30mg, any more should be under supervision.
Agmatine is very useful for mood issues on its own, but it seems to be better when combined with lithium.
GABA lessens depression
Thus, things like vitamin B6, taurine, theanine, valerian root and lemon balm can all be helpful
Vitamin B6 (P5P form is best, 10-15mg is typically ideal, a liquid P5P is best so you can control the dose better). Keith Littlewood sells a great liquid P5P.
Magnesium
Progesterone, Pregnenolone, DHEA, and Allopregnanolone
Improving thyroid function
Other B vitamins (Thiamine, Niacinamide etc…)
Creatine
Carrot salad
Zinc carnosine
Aloe Vera
*None of this is medical advice. I am not a medical professional, always talk to your doctor*
If you enjoyed this article, please consider checking out the other articles I’ve written. Also, please feel free to subscribe (it is free to do so) and share the articles with others. Thank you!
BTW: I am a frequent guest on the podcast “Stuff Your Doctor Should Know”.
Discount code DEAN works at:
Ona’s Naturals (progesterone oil, topical progesterone and pregnenolone creams)
LifeBlud (Magnesium products, Taurine, Theanine, B vitamins, Methylene Blue)
Health Natura (oral pregnenolone, Methylene Blue, Monolaurin)
This has been an incredibly helpful read, thank you!
So insightful. Thank you!