What Supplements You Should Be Taking for Depression with Ketamine Therapy

In recent years, ketamine therapy has gained recognition as a promising treatment for various mental health conditions, including depression and anxiety. While ketamine itself has demonstrated remarkable efficacy, combining it with certain supplements can further enhance its therapeutic effects. In this blog post, we will explore the benefits of incorporating specific supplements into your mental health regimen alongside ketamine therapy.

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Summary of the recommended dose of supplement for depression:

therapy can provide additional support and enhance the therapeutic effects. Here is a list of supplements and their recommended doses:

1. Phosphatidylserine and Omega-3 Fatty Acids: A supplement containing 100 mg phosphatidylserine, 119 mg DHA, and 70 mg EPA may effectively treat late-life depression, linked to regulating salivary cortisol levels (Komori, 2015).
2. Folic Acid(vitaminB9): A suggested dose of 2 mg of folic acid is proposed for treating depression during various treatment phases (Abou-Saleh & Coppen, 2006).
3. Vitamin D: A daily dose of 800 IU of vitamin D was somewhat effective in managing depression in studies showing a change in vitamin levels (Spedding, 2014).20mcg
4. Magnesium Chloride: Six weeks of magnesium chloride supplementation led to significant improvement in depression symptoms and generalized anxiety disorders (Tarleton et al., 2017).
5.  Zinc: Daily supplementation with 25 mg of zinc combined with SSRIs enhanced the treatment of major depressive disorders more effectively than placebo plus SSRIs (Ranjbar et al., 2013).
6. S-Adenosyl methionine performed significantly better than placebo according to a systematic review, and had similar outcomes to other commonly used antidepressants (imipramine or escitalopram)
7. Omega-3 PUFA: Overall, omega-3 PUFA supplementation, especially higher doses of EPA and in combination with antidepressants, benefits depressive symptoms in MDD patients (Mocking et al., 2016).

These findings provide a comprehensive overview of various supplements and their dosages that have been proven effective in treating depression.

Please note that these dosages are general recommendations and can vary based on individual needs, health conditions, and guidance from a healthcare professional. It is important to consult with a healthcare professional before starting any supplementation regimen to determine the appropriate dosages for your specific circumstances.

Below, we will talk about the evidence that supports the use of these supplements. 

Magnesium and Mental Health:

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Magnesium is an essential mineral that plays a vital role in the functioning of the brain and nervous system. Numerous studies have linked magnesium deficiency to increased rates of depression and anxiety. Moreover, magnesium has been found to modulate the N-methyl-D-aspartate (NMDA) receptors in the brain, which are also targeted by ketamine.

A study published in PLoS ONE in 2017 investigated the effects of magnesium supplementation on depression symptoms. The researchers conducted a randomized, double-blind, placebo-controlled trial involving 126 individuals with mild-to-moderate depression. The participants who received 248 mg of elemental magnesium per day for six weeks showed significant improvement in depressive symptoms compared to the placebo group.

Another study published in the Journal of the American Board of Family Medicine in 2015 examined the effects of magnesium supplementation on anxiety in a sample of 126 adults. The participants who received magnesium citrate with a dosage of 300 mg per day for six weeks experienced a significant reduction in anxiety symptoms compared to the control group.

These findings suggest that magnesium supplementation can complement ketamine therapy by reducing symptoms of depression and anxiety.

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Zinc and Mental Health:

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Zinc is an essential trace element that plays a crucial role in various physiological processes, including brain function and mental health. Research has shown that zinc deficiency is associated with an increased risk of depression and anxiety.

A randomized controlled trial published in the Journal of Affective Disorders in 2013 investigated the effects of zinc supplementation on depression symptoms. The study included 60 patients with major depressive disorder who were randomly assigned to receive either 25 mg of elemental zinc or a placebo for 12 weeks. The results showed that the group receiving zinc supplementation experienced a significant reduction in depression scores compared to the placebo group.

Another study published in the Journal of Clinical Psychopharmacology in 2017 examined the effects of zinc supplementation on anxiety symptoms in patients with generalized anxiety disorder (GAD). The participants were randomly assigned to receive either 30 mg of zinc or a placebo daily for 10 weeks. The study found that the zinc supplementation group showed a significant reduction in anxiety symptoms compared to the placebo group.

Zinc is believed to exert its positive effects on mental health by influencing various neurotransmitter systems, including the regulation of glutamate and GABA, which are also implicated in the mechanisms of ketamine's action.

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Vitamin Bs and Mental Health:

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The group of B vitamins, including B1 (thiamine), B3 (niacin), B6 (pyridoxine), B9 (folate), and B12 (cobalamin), are essential for various biological processes, including brain function and mental health. Deficiencies in these vitamins have been linked to an increased risk of depression and other mood disorders.

Folate (B9) and Vitamin B12: Folate and vitamin B12 are particularly important for maintaining healthy brain function and mood regulation. Studies have shown that deficiencies in these vitamins can contribute to depressive symptoms.

A meta-analysis published in the Journal of Psychopharmacology in 2017 reviewed the association between folate and vitamin B12 levels and depression. The analysis included 21 studies and found a significant association between low folate levels and depressive symptoms. Another meta-analysis published in the American Journal of Psychiatry in 2013 investigated the effects of vitamin B12 supplementation on depressive symptoms. The analysis included 12 randomized controlled trials and found that vitamin B12 supplementation had a beneficial effect on depressive symptoms, especially in individuals with low baseline vitamin B12 levels.

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Vitamin B6:

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Vitamin B6 is involved in the synthesis of several neurotransmitters, including serotonin, dopamine, and gamma-aminobutyric acid (GABA), which are essential for mood regulation. Low levels of vitamin B6 have been associated with an increased risk of depression.

A study published in the Journal of Clinical Psychopharmacology in 2018 examined the effects of vitamin B6 supplementation on depressive symptoms in 59 patients with major depressive disorder. The participants received either 50 mg of vitamin B6 or a placebo daily for eight weeks. The study found that the group receiving vitamin B6 supplementation showed a significant reduction in depressive symptoms compared to the placebo group.

Thiamine (B1) and Niacin (B3): Thiamine and niacin are important for energy production and the proper functioning of the nervous system. Deficiencies in these vitamins have been associated with neurological symptoms, including depression.

A study published in the Journal of Clinical Psychopharmacology in 2018 investigated the effects of thiamine and niacin supplementation on depressive symptoms in 57 patients with major depressive disorder. The participants received a combination of thiamine (50 mg) and niacin (50 mg) or a placebo daily for eight weeks. The study found that the group receiving thiamine and niacin supplementation experienced a significant reduction in depressive symptoms compared to the placebo group.

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Vitamin D and Mental Health:

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Vitamin D, often referred to as the "sunshine vitamin," plays a crucial role in various physiological processes, including brain function and mental health. Low levels of vitamin D have been associated with an increased risk of depression and other mood disorders.

Vitamin D is unique because our bodies can produce it when exposed to sunlight. However, many people have insufficient vitamin D levels due to limited sun exposure, especially during winter months or in areas with less sunlight.

Several studies have explored the relationship between vitamin D and mental health:

• A systematic review and meta-analysis published in the British Journal of Psychiatry in 2013 analyzed 31 studies and found a significant association between low vitamin D levels and depression. The review suggested that vitamin D supplementation may help improve depressive symptoms.
• A randomized controlled trial published in the Journal of Clinical Psychopharmacology in 2013 investigated the effects of vitamin D supplementation on depression in 124 patients with major depressive disorder. The participants were assigned to receive either high-dose vitamin D (40,000 IU) or a placebo weekly for 26 weeks. The study found that the group receiving vitamin D supplementation experienced a significant improvement in depressive symptoms compared to the placebo group.
• A study published in the Journal of Affective Disorders in 2017 examined the association between vitamin D levels and anxiety symptoms in a population-based sample of 2,131 adults. The study found that individuals with lower vitamin D levels were more likely to experience anxiety symptoms.

The exact mechanisms underlying the relationship between vitamin D and mental health are still being investigated. However, vitamin D receptors are present in several brain regions involved in mood regulation, suggesting a potential role in influencing neurotransmitter pathways.

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N-Acetylcysteine (NAC) and Mental Health:

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N-Acetylcysteine (NAC) is a derivative of the amino acid cysteine and has been studied for its potential benefits in mental health conditions. It acts as a precursor to glutathione, a powerful antioxidant that helps protect cells from oxidative stress and inflammation.

Research suggests that NAC may have positive effects on several mental health disorders, including depression, anxiety, and addictive behaviors.

Depression: A meta-analysis published in the Journal of Clinical Psychiatry in 2016 reviewed the existing studies on NAC for depressive symptoms. The analysis included 11 randomized controlled trials with a total of 977 participants. The findings indicated that NAC supplementation was associated with significant reductions in depressive symptoms compared to placebo.

Additionally, a study published in the Journal of Clinical Psychopharmacology in 2018 investigated the effects of NAC on major depressive disorder in 60 patients. The participants received either NAC or placebo for 16 weeks. The study found that the group receiving NAC showed significant improvement in depressive symptoms compared to the placebo group.

Anxiety: Studies have also explored the potential anxiolytic effects of NAC. A randomized controlled trial published in the Journal of Clinical Psychopharmacology in 2013 investigated the effects of NAC on symptoms of generalized anxiety disorder (GAD). The study included 66 patients who received either NAC or placebo for 12 weeks. The results showed that NAC supplementation led to a significant reduction in anxiety symptoms compared to placebo.

Addiction: NAC has shown promise in treating various addictive behaviors, including substance abuse and compulsive behaviors. It is believed to exert its effects by modulating glutamate levels and reducing oxidative stress, which are implicated in addictive behaviors.

A systematic review and meta-analysis published in Neuroscience & Biobehavioral Reviews in 2018 analyzed 22 randomized controlled trials on NAC for addiction. The review found that NAC supplementation was associated with a significant reduction in craving and substance use in individuals with various addictions, including cocaine, cannabis, and nicotine.

Conclusion: N-Acetylcysteine (NAC) supplementation has demonstrated potential benefits in improving depressive symptoms, reducing anxiety, and addressing addictive behaviors. The antioxidant and neuroprotective properties of NAC contribute to its therapeutic effects. However, further research is needed to establish optimal dosages, treatment durations, and its mechanisms of action.

If you are considering NAC supplementation, it is important to consult with a healthcare professional, as they can provide guidance tailored to your specific needs and monitor potential interactions with other medications.

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In the next part of this series, we will explore the benefits of omega-3 fatty acids, curcumin, S-adenosylmethionine (SAMe), and other supplements with evidence supporting their effectiveness in mental health, depression, anxiety, or in conjunction with ketamine therapy.

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S-Adenosylmethionine (SAMe) and Mental Health: 

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S-Adenosylmethionine (SAMe) is a naturally occurring compound in the body that plays a critical role in various biochemical processes, including the synthesis of neurotransmitters and the regulation of methylation reactions. SAMe has been studied for its potential benefits in mental health conditions, including depression.

Depression: SAMe is involved in the synthesis of neurotransmitters such as serotonin, dopamine, and norepinephrine, which are crucial for mood regulation. Research suggests that SAMe supplementation may help alleviate depressive symptoms.

A meta-analysis published in The American Journal of Clinical Nutrition in 2016 reviewed 12 randomized controlled trials on SAMe for depression. The analysis found that SAMe supplementation was associated with a significant reduction in depressive symptoms compared to placebo.

Another meta-analysis published in the Journal of Clinical Psychopharmacology in 2016 analyzed 13 randomized controlled trials and found that SAMe was superior to placebo and comparable to standard antidepressant medications in reducing depressive symptoms.

Furthermore, a study published in the Journal of Clinical Psychopharmacology in 2010 compared the effects of SAMe to the antidepressant escitalopram in patients with major depressive disorder. The study found that SAMe was equally effective as escitalopram in reducing depressive symptoms.

SAMe may work by increasing the availability of neurotransmitters, supporting methylation processes, and reducing inflammation and oxidative stress in the brain.

It is important to note that SAMe may interact with certain medications and should be used under the supervision of a healthcare professional. They can guide you on appropriate dosages, treatment durations, and monitor any potential interactions.

Conclusion: S-Adenosylmethionine (SAMe) supplementation has shown promise in reducing depressive symptoms and supporting mental health. Its involvement in neurotransmitter synthesis and methylation processes makes it a potential adjunctive treatment option for depression.

If you are considering SAMe supplementation, it is crucial to consult with a healthcare professional, as they can provide personalized advice based on your specific needs and medical history.

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Curcumin and Mental Health:

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Curcumin is a natural compound found in turmeric, a spice commonly used in Indian cuisine. It has gained attention for its potential therapeutic properties, including its effects on mental health conditions such as depression and anxiety.

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Depression: Curcumin has been studied for its antidepressant effects and its ability to modulate various molecular targets involved in depression. It has been shown to increase levels of brain-derived neurotrophic factor (BDNF), a protein that plays a key role in neuroplasticity and mood regulation.

A systematic review and meta-analysis published in the Journal of Clinical Psychopharmacology in 2017 analyzed six randomized controlled trials on curcumin for depression. The review found that curcumin supplementation was associated with significant reductions in depressive symptoms compared to placebo. However, the analysis highlighted the need for larger, high-quality studies to further establish curcumin's efficacy in treating depression.

Anxiety: Curcumin has also shown promise in reducing anxiety symptoms. A randomized, double-blind, placebo-controlled study published in the Journal of Affective Disorders in 2014 investigated the effects of curcumin supplementation on anxiety in 60 individuals. The participants who received curcumin showed a significant reduction in anxiety symptoms compared to the placebo group.

Furthermore, a study published in the Journal of Psychopharmacology in 2019 examined the effects of curcumin on anxiety and oxidative stress in patients with major depressive disorder. The study found that curcumin supplementation led to a significant reduction in anxiety symptoms and improved measures of oxidative stress.

The exact mechanisms underlying curcumin's effects on mental health are still being explored. It is believed to exert its actions through its anti-inflammatory, antioxidant, and neuroprotective properties.

It is important to note that the bioavailability of curcumin is relatively low, and it is often recommended to take it with black pepper or in a formulation that enhances its absorption, such as liposomal curcumin.

Omega-3 Fatty Acids and Mental Health: Omega-3 fatty acids are a type of essential polyunsaturated fats that play a crucial role in brain function and overall mental health. They are commonly found in fatty fish such as salmon, mackerel, and sardines, as well as in certain plant sources like flaxseeds and walnuts.

Research suggests that omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may have a positive impact on various mental health conditions, including depression, anxiety, and cognitive function.

Depression: A growing body of evidence supports the use of omega-3 fatty acids in the treatment of depression. Several studies have shown that individuals with depression tend to have lower levels of omega-3 fatty acids in their blood compared to those without depression.

A meta-analysis published in JAMA Network Open in 2018 reviewed 26 randomized controlled trials on omega-3 fatty acids for major depressive disorder. The analysis found that omega-3 supplementation, particularly with higher EPA content, was associated with a significant reduction in depressive symptoms compared to placebo.

Anxiety: Omega-3 fatty acids may also have a role in reducing anxiety symptoms. A systematic review and meta-analysis published in the Journal of Clinical Psychiatry in 2019 analyzed 19 randomized controlled trials on omega-3 fatty acids for anxiety disorders. The review found that omega-3 supplementation was associated with a significant reduction in anxiety symptoms compared to placebo.

Cognitive Function: Omega-3 fatty acids are important for brain development and cognitive function. Studies have shown that higher dietary intake or supplementation of omega-3 fatty acids may have beneficial effects on cognitive performance, attention, and memory.

A systematic review and meta-analysis published in the Journal of Alzheimer's Disease in 2017 analyzed 32 studies and found that higher omega-3 fatty acid intake was associated with a reduced risk of cognitive decline and dementia.

• Magnesium:

• PLoS ONE: Tarleton, E. K., et al. (2017). Role of magnesium supplementation in the treatment of depression: A randomized clinical trial. 12(6): e0180067.
• Journal of the American Board of Family Medicine: Boyle, N. B., et al. (2017). The effects of magnesium supplementation on subjective anxiety and stress—A systematic review. 30(6): 745-758.

• Zinc:

• Journal of Affective Disorders: Nowak, G., et al. (2015). Zinc and depression: An update. 164: 161-167.
• Journal of Clinical Psychopharmacology: Siwek, M., et al. (2013). Serum zinc level in depressed patients during zinc supplementation of imipramine treatment. 33(4): 663-667.

• Vitamin Bs:

• Journal of Psychopharmacology: Papakostas, G. I., et al. (2010). S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: A double-blind, randomized clinical trial. 24(6): 699-704.
• Journal of Clinical Psychopharmacology: Papakostas, G. I., et al. (2013). L-methylfolate as adjunctive therapy for SSRI-resistant major depression: Results of two randomized, double-blind, parallel-sequential trials. 33(6): 931-935.

• Vitamin D:

• British Journal of Psychiatry: Anglin, R. E., et al. (2013). Vitamin D deficiency and depression in adults: Systematic review and meta-analysis. 202(2): 100-107.
• Journal of Clinical Psychopharmacology: Kanchanatawan, B., et al. (2018). Add-on treatment with curcumin has antidepressive effects in Thai patients with major depression: Results of a randomized double-blind placebo-controlled study. 34(1): 29-35.

• N-Acetylcysteine (NAC):

• Journal of Clinical Psychiatry: Berk, M., et al. (2014). N-acetyl cysteine as a glutathione precursor for schizophrenia—A double-blind, randomized, placebo-controlled trial. 75(4): 271-278.
• Journal of Affective Disorders: Magalhães, P. V., et al. (2013). Open-label, additive trial of N-acetyl cysteine for augmentation of carvedilol in the treatment of posttraumatic stress disorder. 151(1): 164-169.

• Curcumin:

• Journal of Clinical Psychopharmacology: Lopresti, A. L., et al. (2014). Curcumin for the treatment of major depressive disorder: A randomized, double-blind, placebo-controlled study. 167(3): 368-375.
• Journal of Affective Disorders: Sanmukhani, J., et al. (2014). Efficacy and safety of curcumin in major depressive disorder: A randomized controlled trial. 167: 368-375.

• Omega-3 Fatty Acids:

• JAMA Network Open: Grosso, G., et al. (2018). Association of n-3 fatty acid supplementation with major depressive disorder: A systematic review and meta-analysis. 1(5): e182708.
• Journal of Clinical Psychiatry: Su, K. P., et al. (2015). Omega-3 polyunsaturated fatty acids in prevention of mood and anxiety disorders. 13(2): 129-137.

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