Natural Supplements, Nutrition, and Behavioural Strategies for Depression

May 12, 2024 Dr Harry

This article is aimed at addressing nutritional deficiencies, supplementation and the fundamental behaviours that can be used for the remedy of depressed mood states. These are relevant for severe depression, e.g. clinically diagnosed major depressive episodes, as well as the more common and mild, yet pervasive depressed mood states characterised by low mood and/or anhedonia (lack of motivation/pleasure)—both of which may be accompanied by difficulty focusing, lethargy, sleep disturbances, hopelessness etc. The nutritional deficiencies addressed in this segment will be that of micronutrients (vitamins, macro minerals, trace minerals and organic acids); macronutrients in the form of fats, carbohydrates, protein and overall calorie consumption will not be addressed here.

*Please note, although I am a clinical doctor myself, I strongly advise against the SELF-administration of all of the supplements and protocols mentioned below. This article is purely for educational purposes, serving as a useful resource to point each of you in the right direction when consulting with a specialist clinician in this area.*

Natural Supplements and Nutrition

Vitamin B: B vitamins, a group of eight water-soluble coenzymes, play crucial roles in metabolism and are found in many raw foods. Deficiencies can lead to various health issues, including depression. Depressive symptoms often accompany low levels of B vitamins, specifically B12, B6, and B9 (folic acid), with research suggesting that higher intake of these B vitamins may lower depression risk, although it's unclear if they prevent it. To note, it's a common occurrence for individuals to have a mutation in the gene responsible for converting folic acid into its biologically active form. So, if wanting to supplement for this, it's safer to supplement with 5-MTHF, the active form of folic acid, which can be bought as a supplement. This will be the safest bet if looking to achieve clinical benefit.

Homocysteine: Homocysteine is an amino acid, which when levels are high for extended periods of time, can cause considerable damage to the inner linings of our blood vessels, which may give rise to a range of cardiovascular conditions. Besides this, high levels of homocysteine are linked to those with depression, and are thought to be partially responsible for it, as well as its association with cognitive decline. The reduction of these levels can be easily achieved by the supplementation of the aforementioned Vitamin B6, B12, and B9 (Folic acid). As mentioned earlier, the biologically active form of folate is a the safer form of supplementation. The bioactive form of folate is 5-MTHF. Daily doses of 1,000 mcg to 5,000 mcg of bioactive folate are typically used in studies to achieve a clinically beneficial reduction in homocysteine levels.

S-adenosyl methionine (SAMe): Reduction of SAMe levels are often seen in those with depression. This is another critical amino acid, which acts as a ‘methyl donor’ and plays a crucial role in our metabolism and synthesis of mood-enhancing neurotransmitters. Its deficiency may be in part due to the observation of the reduction of Vitamin B12 and folate that is seen for those with depression; these vitamins are needed in the formation of SAMe. Studies on the therapeutic effect of supplementing with SAMe (dosages ranging from 800mg to 3200mg daily) have shown SAMe to be effective in the treatment of depression, and that it is safe to be used in combination with antidepressant treatment. More research is needed to further study its efficacy and safety, but the results to date are very promising.

Saffron: A recent meta-analysis assessed the impact of saffron supplementation on symptoms of depression and anxiety across various populations, including adults, adolescents, and those with subclinical conditions. It built on findings from earlier studies, confirming saffron's significant positive effects on both depression and anxiety when compared to placebo. Specifically, saffron showed considerable efficacy as both a standalone and an adjunctive treatment in depressive disorders, with no significant differences when compared directly with antidepressants. Most studies administered saffron supplementation at a dose of 30mg/day. However, the analysis also concluded that the studies to date had limitations (e.g. small sample sizes and short durations), therefore more well-controlled studies are needed to better judge its long-term benefit and safety profile.

Vitamin D: Though indiscriminate supplementation with Vitamin D has not proven effective at relieving symptoms for those experiencing depression, low vitamin D levels are significantly associated with depressed mood. Therefore, the correction of these levels, if suboptimal, is generally advised for good health.

Magnesium: Magnesium is crucial for over 300 cellular functions and the body’s inflammatory defence mechanisms. A deficiency in magnesium can lead to overactivity of N-methyl-D-aspartate (NMDA), which is associated with depressive symptoms and neuroendocrine alterations. Studies indicate that adults with depression often have lower serum magnesium levels. Eleven studies have linked magnesium supplementation with a decrease in depressive symptoms, showing a statistically significant effect. This beneficial outcome was primarily observed in uncontrolled studies, where the effect size was notably larger, but was not evident in placebo-controlled studies. The variations in the dosage of magnesium in these studies (ranging from 225 to 4000 mg) and the duration of treatment (1 to 12 weeks) did not correlate with the changes in depressive symptoms. It’s reasonable to conclude from this that magnesium supplementation can be therapeutic, but to be more certain of its potential benefit, more controlled studies are warranted.

Selenium: This is a trace element which plays a critical role in mood regulation, though its exact mechanisms remain unclear. Selenium is understood to have antioxidant, anti-inflammatory, immunomodulatory, and neuroprotective properties. Studies generally do not support observation of deficiency in serum levels of selenium for those with depression compared to healthy subjects, however the few studies looking into the effects of supplementation of this element for those with depression have generally demonstrated a symptom reduction and enhancement in mood scores.

Coenzyme Q10: A vitamin-like molecule, that plays a crucial role as a potent antioxidant and in the formation of ATP in the mitochondria, which is the molecule that provides us with energy. Research to date demonstrates the link between low serum levels of this enzyme and states of depression. The studies on this are limited in number, often including participants who were experiencing depression as a consequence of physical health disorders, or Bipolar Affective Disorder. Nevertheless, supplementation in these cases has proven effective, and therefore further studies investigating its potential in alleviating symptoms in those with unipolar depression is warranted.

Curcumin: A substance which is extracted from the spice turmeric has been investigated for its potential use in multiple mood disorders, including depression. Studies to date generally show a modest improvement in symptoms for subjects taking curcumin when compared to placebo. The doses given from what the studies I have read ranged from 200mg to 1000mg daily and they were usually tested over the course of 8 weeks.

Zinc: Research into zinc was provoked by the observation of the strong connection between individuals with low zinc levels and depression. So far, zinc supplementation has shown to be effective in the treatment of depression—with the more convincing effects being when used in combination with antidepressants.

Acetylcarnitine: Again, research into this was prompted by the role that a deficiency in levels of acetylcarnitine has, in increasing the risk of developing depression. A major meta-analysis on this concluded supplementation of acetylcarnitine shows significant reduction in depressive symptoms when compared to placebo groups.

Creatine: 1g-5g creatine monohydrate daily. This is an amino acid which is often known for its use by those who resistance train. But there are promising results from literature so far pointing to its mood-enhancing effects (thought to be due to its effect on the dopamine pathway). Majority of these studies included augmenting creatine with the participants' regular antidepressant medication.

Inositol: This is a sugar alcohol which is abundant in the brain. With comparatively large doses taken daily, its effects have been promising in preliminary trials. However, there aren’t many of them, and results are mixed.

Omega 3 Fatty Acids: Specifically in the form of EPA (DHA has not shown to be effective). The minimal dose recommended is relatively high at 1000mg EPA daily, which is still possible to acquire in capsule form. It’s observed positive effects on mood are thought to be a consequence of anti-inflammatory properties. The systematic reviews performed on EPA, have been critical of the quality of studies to date—but the general consensus is that there appears to be a modest benefit to taking EPA for those with depression.

Lavender: A major meta-analysis performed in 2021 concluded that lavender was effective in reducing symptoms for those with depression. Lavender is often used in aromatherapy, making it hard to judge the effects lavender may have on its own, but some of the studies included its administration orally via capsules (of either 1000mg lavender flower powder daily or 80mg of lavender oil daily). The general consensus is that lavender does indeed exert therapeutic effects, but the study designs to date are often flawed.

N-acetylcysteine: Otherwise known as NAC. Used commonly to reverse paracetamol overdoses, this particular compound is emerging as having a modest improvement in depression alongside other mood disorders. Again most likely due to its anti-inflammatory role.

Rhodiola Rosea: A clinical trial assessing the efficacy and safety of the SHR-5 extract from Rhodiola rosea L. in treating mild to moderate depression demonstrated significant improvements in depression, insomnia, emotional instability, and somatisation for the treatment groups, with no improvement in the placebo group and no serious side effects reported. Conducted over six weeks, participants were divided into three groups: Group A received 340 mg/day of SHR-5, Group B received 680 mg/day, and Group C received a placebo. This is just one trial; there have been a few more, but more evidence is needed to come to any confident conclusions. However, the results to date are promising.

N.B: Some emerging treatment options I have not included are Tryptophan, 5-HTP, St. John's Wort, Lion's Mane, Calcium, L-Tyrosine, and L-Theanine. These were excluded either because the evidence base is still limited, potential side effects, or the benefits from taking these are relatively minor based on the literature I’ve reviewed.

Behavioural Approaches

The fundamentals. These are habits that we really need to ensure we do consistently. I’m going to avoid citing studies when possible here, as purely studying these behaviours as potential treatments for depression is far too simplistic. For example, to just quote a study reporting the findings that exercise is as good as antidepressants for the treatment of depression is futile. The effects of regular exercise is multifaceted, and these effects compound over longer durations. We often meet our closest friends exercising, we build discipline and resilience, and over longer periods of time simply getting in shape lends to being a more competent and confident individual. These are just a few components that are not served justice when performing targeted studies over a short period of time. This applies to many of the positive routines and factors that are essential to our general well-being, hence my hesitance to reference studies (of which there are many). Fundamental factors include, though are not limited too:

A job - Providing us with an anchor amongst the unpredictability of life. We all need some form of structure, a creative purpose, or even someone or something we feel responsible for.

Exercise - 3 hours a week is most commonly recommended. It improves our mood, confidence, resilience, and what is also clear is that it leads to a reduction in the biological response to acute psychological distress.

Relationships - We’re social animals, it’s in our nature to reach out. Without the meaningful connections that come with deeper relationships, it’s not abnormal to then experience the negative emotions associated with depression.

Sleep/Wake Cycle/Light- For Sleep, 7-9 hours is the gold standard recommendation. Sleeping at the right time is also crucial (10pm is ideal), as this impacts not only our quality of sleep but can help to ensure adequate sunlight exposure during the day time. As it relates to the importance of bright light- most emphasis so far understandably has been on the effects bright light therapy has on people with seasonal affective disorder (for which it has shown to be very effective). Bright light therapy typically consists of someone sitting in close proximity to a 10000 lux light box for 30 minutes daily in the morning. The causes of SAD are not completely understood, but what is clear is the overlap between SAD and typical depression, specifically as it relates to serotonin. In SAD there seems to be more specific abnormalities in the circadian rhythm shifts that healthy individuals rely on when shifting between seasons, but what’s interesting is bright light therapy appears to provoke an increase in the availability of serotonin. This is why, although not a lot of quality research has been performed for its uses in other mood disorders, including unipolar depression, the results are promising so far.

Mindfulness Practices - Done regularly, these work most effectively in dampening the cognitive component of depression (thoughts of panic, grief, hopelessness, etc.). A lot of what drives, really any unpleasant thought or feeling, is simply the identification with it. This intimate association we have, on an almost continual basis, with the content of our minds is often the root of much of our suffering—and this is especially true with specifically the cognitive aspects of depression. The ability to detach from the negative self-talk, common in depression, comes with deliberate practice, which most reliably comes in the form of mindful meditation practices.

That wraps up this exploration into supplementation, nutritional deficiencies and behavioural factors useful to note for those prone to depressed mood states. For any questions relating to the information above, please feel free to reach out to myself- I’m always more than happy to help.

Resources

*(not all of the studies have been included, due to the sheer number referred too—they will of course be available upon request)*

https://www.tandfonline.com/doi/full/10.1179/1476830515Y.0000000002 coenzymeq10

https://journals.lww.com/psychopharmacology/abstract/2018/10000/evaluating_the_effect_of_coenzyme_q10_augmentation.9.aspx

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769464/creatine

https://www.tandfonline.com/doi/full/10.1080/10408398.2019.1653260 curcumin

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612309/pdf/CD004692.pdfomega3

https://www.nature.com/articles/s41598-022-05078-1selenium

https://www.eurekaselect.com/article/78435vitB

https://ajp.psychiatryonline.org/doi/10.1176/ajp.152.5.792?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmedinositol

https://journals.lww.com/psychosomaticmedicine/abstract/2018/02000/acetyl_l_carnitine_supplementation_and_the.4.aspx

https://www.sciencedirect.com/science/article/pii/S0965229921000200?via%3Dihub lavender