New research on depression, and a new look at supplements for mood and sleep disorders

At the end of 2013, there was much buzz about new studies showing that curing insomnia in people with depression might double the chance of a complete recovery from depression. The studies, financed by the National Institute of Mental Health, were welcomed as the most significant advance in treating depression since the introduction of the “selective serotonin re-uptake inhibitor” (SSRI), Prozac, twenty-five years ago. In effect, the new research findings turn conventional wisdom on its head, since they suggest that insomnia can be a main cause of depression, rather than just a symptom or a side effect, as previously assumed. If you can successfully treat a depressed person’s insomnia, according to the new view, you eliminate one of the main factors causing the depressed state.

New research findings turn conventional wisdom on its head
suggesting that insomnia can be a main cause of depression
rather than just a symptom or a side effect as previously assumed

As we followed reports on this breakthrough research on insomnia and depression, we were especially encouraged to read comments like the one from Washington DC psychiatrist James Gordon, who has advocated an integrative approach to treating depression. Here’s his letter to The New York Times: 

I welcome a new report’s finding that cognitive behavioral therapy is improving the outcome for depressed people with significant insomnia (“Sleep Therapy Seen as an Aid for Depression,” front page, Nov. 19). 

It reminds us that changes in attitude and perspective, and a therapeutic relationship, can right biological imbalances — like disordered sleep — and significantly enhance the lives of troubled people. The study also puts the therapeutic role of antidepressant medication in perspective: the depressed participants who received behavioral therapy did equally well whether or not they were taking the drugs. 

I hope that these results will encourage the National Institute of Mental Health, researchers, clinicians and all of us to expand our horizons. 

There are a number of other nonpharmacological therapies, including meditation, physical exercise, dietary change and nutritional supplementation, acupuncture and group support, that show promise for improving clinical depression and enhancing brain function.

At NYBC we have long believed that non-prescription therapies, such as supplements, are valuable alternatives for treating mood disorders and sleep disorders When the Centers for Disease Control surveyed use of antidepressant drugs in 2008, it found that one in 10 Americans was taking an antidepressant, and many had taken these drugs for years. Over a period of ten years, antidepressant use in the U.S. had shot up by 400%! So the question arises: how much of this spectacular increase represented real gains in treatment, and how much was over-prescribing? As Dr. Gordon mentions in his letter above, in some cases behavioral therapy for depression has worked just as well whether people were taking antidepressants or not—hardly a strong argument for the value of the prescription drugs.

A well-publicized 2008 report in the New England Journal of Medicine
found that pharmaceutical companies had consistently reported

only the most favorable trial outcomes for their popular antidepressants

A well-publicized 2008 report in the New England Journal of Medicine found that pharmaceutical companies had consistently reported only the most favorable trial outcomes for their popular antidepressants, passing over evidence that suggested a more limited effectiveness. Furthermore, as with many drugs, especially those used over a long period, antidepressants have side effects. Higher bone fracture risk and multiple cardiovascular risks have been identified; sexual side effects are common with antidepressants in both men and women; and withdrawal symptoms for those tapering off antidepressants include a long list of problems, such as panic attacks, insomnia, poor concentration and impaired memory.

Turning to the alternatives, we describe below supplements that NYBC has highlighted over the years for sleep and mood disorders. Note cautions about their use, but also note that some of these products may actually carry added benefits, rather than unwanted side effects.

1. Melatonin is a hormone occurring naturally in the body, but some people who have trouble sleeping have low melatonin levels. Melatonin has been used for jet lag, for adjusting sleep-wake cycles for people doing shift work on varying schedules, and for insomnia, including insomnia due to high blood pressure medications called beta-blockers. It is also used as a sleep aid when discontinuing benzodiazepines (Klonopin, Xanax, etc.) and to reduce side effects when quitting smoking.

2. Fish Oil. Epidemiologists have noted that populations that eat fish regularly have low rates of depression. And research has found that omega-3 fatty acids in fish oil supplements can be of benefit in treating depression and bipolar disorder. Fish oil can also be taken with other anti-depressants as an adjunct therapy. Doses found effective in treating depression are quite high, 3 to 9 grams per day, so be aware of potential problems related to the supplement’s blood-thinning properties. Added benefit: fish oil can help manage cholesterol, and supports cardiovascular health.

3. Deficiencies in the B Vitamins, especially B12 and folate, can result in neurologic symptoms — for example, numbness, tingling and loss of dexterity — and the deterioration of mental function, which causes symptoms such as memory loss, confusion, disorientation, depression, irrational anger and paranoia. A number of studies have shown that vitamin B12 is deficient in a large percentage of people with HIV, and the deficiency can begin early in the disease. Supplementing with a B complex protects against deficiency and supports cognitive health and mental function.

4. Vitamin D deficiency has also been linked to depressed states. Lack of the “sunshine vitamin” may be especially associated with Seasonal Affective Disorder (SAD), the “winter blues.” Vitamin D also supports bone health, and may protect against colds and flus.

5. Theanine, an amino acid found in green tea, acts as a relaxing agent by increasing levels of certain neurotransmitters (=brain chemicals that shape your mood), including serotonin, dopamine, and GABA (gamma amino butyric acid). Human studies have been limited to date, but one small study showed that theanine decreases stress responses such as elevated heart rate. Another investigation compared theanine’s calming effect to that of a standard anti-anxiety prescription drug, and found that theanine performed somewhat better. Note that NYBC stocks Theanine Serene (Source Naturals), a combination supplement that includes theanine and GABA.

6. Probiotics. Very recent research has looked into the communication between the digestive system and the brain, with a goal of understanding how gut health may influence chronic conditions, including mood disorders like depression and anxiety. For example, it has been shown that certain probiotics promote production of the calming, anti-stress neurotransmitter GABA in the body, pointing to a direct influence of probiotics on mood. Other potential links between the gastrointestinal system’s microorganisms and brain function are currently being explored.

7. L-Tryptophan and 5-HTP (5-hydroxy L-tryptophan). These closely related supplements are converted in the body to serotonin and to melatonin. (Take L-tryptophan with carbohydrates to make it effective.) Their use as antidepressants has been studied, and they have also been found to aid sleep and suppress appetite. (To minimize appetite suppression, take the supplement an hour before bedtime.)  Although L-Tryptophan and 5-HTP are close relatives, people may respond somewhat differently to them, so it may be worthwhile to try the other if the first doesn’t produce an effect An added benefit: 5-HTP may also decrease symptoms of fibromyalgia and migraine headaches.

8. In research funded by the National Institute of Mental Health, DHEA (dehydroepiandrosterone) was found to be an effective therapy for mild-to-moderate or severe midlife depression, on par with some prescription drugs. Moreover, the research showed that taking DHEA promoted both a significant lifting of depressive symptoms and an improvement in sexual functioning. Note that dosing recommendations vary for men versus women, and DHEA is not recommended for those diagnosed with prostate conditions or cancer.

9. SAMe (S-adenosyl-l-methionine) is produced naturally in the body from the amino acid methionine. Supplementing with SAMe increases concentrations of the neurotransmitters serotonin and dopamine. Several studies show SAMe having an antidepressant effect comparable to that of some prescription drugs. SAMe should be avoided in people with bipolar disorder, and should be used cautiously with other antidepressants, because the combination may push serotonin levels too high. Taking a B-complex vitamin while using SAMe can counter build-up of homocysteine, which has been linked to heart disease SAMe may also support joint health and liver function. Caution: the National Center for Complementary and Alternative Medicine has posted a warning that SAMe may increase likelihood of pneumocystis infection in immune-compromised people. Note: see also Trimethylglycine (TMG), which includes the raw materials that the body uses to manufacture SAMe. TMG is much less expensive than SAMe.

10. St. John’s Wort is a widely used herb with clinically demonstrated (multiple, well-controlled studies, mostly in Europe) anti-depressant effects for mild to moderate depression – generally without the side effects of prescription antidepressants. High doses of the herb may cause a sensitivity to light (phototoxicity), so avoid direct sunlight or sunbathing while using. Do not take St. John’s Wort with 5-HTP, serotonin re-uptake inhibitors (like Prozac), or with protease inhibitors, as it may affect beneficial liver enzymes. St. John’s Wort may also have activity against Epstein-Barr and herpes infections.

11. Finally, we’ll mention another combination supplement that NYBC has stocked: GABA Soothe (Jarrow). The GABA in this supplement is the neurotransmitter that promotes calmness coupled with mental focus. Also included is theanine (see above for a description of its anti-anxiety effects) and an extract of ashwagandha, an herb which has long been used in the Ayurvedic tradition of India to reduce fatigue and tension associated with stress.

 

supplement-header-2014
This article from the Spring 2014 edition of SUPPLEMENT: Newsletter of the New York Buyers’ Club, available for download at http://www.NewYorkBuyersClub.org

 

References:

CDC statistics on antidepressant use in the US, 2005-2008: http://www.cdc.gov/nchs/data/databriefs/db76.htm

Turner, E et al. Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy. New England Journal of Medicine,  2008; 358:252-260 January 17, 2008 doi: 10.1056/NEJMsa065779

Logan, A.. Omega-3 fatty acids and major depression: A primer for the mental health professional. Lipids Health Dis. 2004; 3: 25; doi:  10.1186/1476-511X-3-25

Sudden cardiac death secondary to antidepressant and antipsychotic drugs, Expert Opinion on Drug Safety, March 2008; 7(2):1081-194

Alramadhan E et al. Dietary and botanical anxiolytics Med Sci Monit. 2012 Apr;18(4):RA40-8.

Rogers PJ, Smith JE, Heatherley SV, Pleydell-Pearce CW. Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together. Psychopharmacology (Berl) 2008;195(4):569–77.

Kimura, K et al. L-Theanine reduces psychological and physiological stress responses. Biol Psychol. 2007 Jan;74(1):39-45.

National Center for Complementary and Alternative Medicine at NIH. S-Adenosyl-L-Methionine (SAMe): An Introduction Accessed at http://nccam.nih.gov/health/supplements/SAMe

Carpenter, D J. St. John’s wort and S-adenosyl methionine as “natural” alternatives to conventional antidepressants in the era of the suicidality boxed warning: what is the evidence for clinically relevant benefit? Altern Med Rev. 2011 Mar;16(1):17-39.

Foster, J A et al. Gut-brain axis: how the microbiome influences anxiety and depression Trends in Neuroscience. 2013 May;36(5):305-12. doi: 10.1016/j.tins.2013.01.005.

Rao, A V & Bested, A. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009; 1: 6 doi:  10.1186/1757-4749-1-6

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Omega-3 fatty acids and brain health

A recent study published in the Journal of the American Heart Association looked at the relationship between consumption of omega-3 polyunsaturated fatty acids and some physical measures of the brain that have been linked to “brain health” and “cognitive health.” This research was a bit different from many other studies of omega-3 fatty acids and potential health benefits, because most other studies have looked for relationships between dietary intake of these compounds (found especially in deep water fish like salmon, sardines, tuna, and mackerel) and major health outcomes, such as cardiovascular disease or depression. The JAHA article, on the other hand, narrowed the focus by examining measurable small-scale physical changes in the brain over a period as long as five years.

The results: people with higher omega-3 fatty acid levels showed a significantly lower number of the small-scale physical brain changes that may be associated with brain dysfunction or cognitive decline.
The study authors concluded that, among the older men and women who were the study’s subjects, higher blood levels of omega-3 fatty acids, “and in particular DHA, were associated with specific findings consistent with better brain health.”

Our comment: a fascinating study, because it adds another level of evidence contributing to the already widely accepted view that omega-3 fatty acids are beneficial for your brain, and indeed may provide important help in maintaining brain function as you age.

See the NYBC catalog for a selection of fatty acids, and note especially the Nordic Naturals Pro Omega choices, which are excellent quality fish oil supplements, containing the omega-3 polyunsaturated fatty acids studied in the JAHA article:

FATTY ACIDS in the NYBC CATALOG

Of special interest is the Jarrow supplement Max DHA, which provides an enhanced dose of the omega-3 fatty acid often associated with brain health:

MAX DHA (Jarrow)

Reference:

Virtanen JK, Siscovick DS, Lemaitre RN, Longstreth WT, Spiegelman D, Rimm EB, King IB, & Mozaffarian D (2013). Circulating omega-3 polyunsaturated fatty acids and subclinical brain abnormalities on MRI in older adults: the Cardiovascular Health Study. Journal of the American Heart Association, 2 (5) PMID: 24113325

“Natural mood enhancer”: Trimethylglycine (TMG)

Trimethylglycine (TMG for short) has been described as a “natural mood enhancer” by Dr Hyla Cass, a practicing physician who’s long advocated for more integrative approaches to mood disorders. That’s because TMG provides the raw materials that the body can use to manufacture S-adenosylmethionine (SAMe). SAMe, as you might know from reading other entries on this Blog, is a well-researched supplement with antidepressant effects comparable in some studies to prescription antidepressants. TMG is also a lot cheaper than SAMe! Cautions: Dr. Cass stresses the importance of being under a doctor’s supervision if using TMG while taking prescription antidepressants, since an excessive build up of the neurotransmitter serotonin is possible. Also note cautions about TMG’s potential role in bacterial growth, which has led to the recommendation not to use during an infection.

For more information on TMG, including dosage recommendations, see

http://nybcsecure.org/product_info.php?cPath=50&products_id=97

Supplements have a role in treating depression/sleep disorders

As 2013 drew to a close, there was much buzz about new studies showing that curing insomnia in people with depression might double the chance of a complete recovery from depression. The studies, financed by the National Institute of Mental Health, were welcomed as the most significant advance in treating depression since the introduction of Prozac 25 years ago. In effect, the new research findings turn conventional wisdom on its head, since they suggest that insomnia may be a main cause of depression, rather than just a symptom or a side effect, as has usually been assumed. So, if you can successfully treat a depressed person’s insomnia, you may be eliminating one of the main factors causing the depressed state.

As we followed news stories about this breakthrough research on insomnia and depression, we were especially encouraged to read comments from Washington DC psychiatrist James Gordon, who has advocated for an integrative approach to treating depression. Here’s his letter to the New York Times:

I welcome a new report’s finding that cognitive behavioral therapy is improving the outcome for depressed people with significant insomnia (“Sleep Therapy Seen as an Aid for Depression,” front page, Nov. 19).

It reminds us that changes in attitude and perspective, and a therapeutic relationship, can right biological imbalances — like disordered sleep — and significantly enhance the lives of troubled people. The study also puts the therapeutic role of antidepressant medication in perspective: the depressed participants who received behavioral therapy did equally well whether or not they were taking the drugs.

I hope that these results will encourage the National Institute of Mental Health, researchers, clinicians and all of us to expand our horizons.

There are a number of other nonpharmacological therapies — including meditation, physical exercise, dietary change and nutritional supplementation, acupuncture and group support — that show promise for improving clinical depression and enhancing brain function.

It is time to undertake authoritative studies of integrative approaches that combine these therapies, perhaps as well as behavioral therapy, in the treatment of both depression and insomnia.

JAMES S. GORDON
Washington, Nov. 19, 2013
The writer, a psychiatrist, is the author of “Unstuck: Your Guide to the Seven-Stage Journey Out of Depression.”

We at NYBC have long been interested in exploring research on supplements and mood disorders, and supplements and sleep disorders. In fact, you’ll find these categories of supplements in a single section of our catalog, at

Supplements for Mood and Sleep Disorders

Please feel free to browse this section, and learn more about supplements such as melatonin, theanine, SAMe, DHEA, and others. There is considerable research on many of these already published, and we believe they will have a role to play in a new, more integrative treatment strategy for depression.

Why Vitamins B12 and D3 Are Especially Important to People with HIV

Our friends at the Canadian AIDS Treatment Information Exchange (CATIE), a Canadian government-supported education and prevention organization, recently published an excellent guide to managing HIV medication side effects. This online guide covers the territory from body shape changes, to gastrointestinal disorders, to neurological effects, to emotional wellness, to fatigue, to sexual difficulties.

The Appendix to this guide focuses on two vitamins, both of which have been highlighted as especially important for people with HIV: B12 and D3. Deficiency of these two vitamins appears to be common among people with HIV, and supplementing to correct the deficiency can bring about major improvements in health. So it’s definitely worthwhile to check your B12 and D3 status, and, if you’re deficient, find a good supplementation strategy. Note that NYBC stocks both of these inexpensive vitamins: the methylcobalamin form of Vitamin B12 recommended below; and several strengths of Vitamin D3, including the commonly recommended D3 – 2500IU format.

Below are the CATIE recommendations:

Vitamin B12

A number of studies have shown that vitamin B12 is deficient in a large percentage of people with HIV, and the deficiency can begin early in the disease. Vitamin B12 deficiency can result in neurologic symptoms — for example, numbness, tingling and loss of dexterity — and the deterioration of mental function, which causes symptoms such as foggy thinking, memory loss, confusion, disorientation, depression, irrational anger and paranoia. Deficiency can also cause anemia. (See the section on Fatigue for more discussion of anemia.) It has also been linked to lower production of the hormone melatonin, which can affect the wake-sleep cycle.

If you have developed any of the emotional or mental symptoms mentioned above, especially combined with chronic fatigue, vitamin B12 deficiency could be contributing. This is especially true if you also have other symptoms that this deficiency can cause, including neuropathy, weakness and difficulty with balance or walking. On the other hand, these symptoms can also be associated with HIV itself, with hypothyroidism or advanced cases of syphilis called neurosyphilis. A thorough workup for all potential diagnoses is key to determining the cause.

Research at Yale University has shown that the standard blood test for vitamin B12 deficiency is not always reliable. Some people who appear to have “normal” blood levels are actually deficient, and could potentially benefit from supplementation.

The dose of vitamin B12 required varies from individual to individual and working with a doctor or naturopathic doctor to determine the correct dose is recommended. Vitamin B12 can be taken orally, by nasal gel or by injection. The best way to take it depends on the underlying cause of the deficiency, so it’s important to be properly assessed before starting supplements. For oral therapy, a typical recommendation is 1,000 to 2,000 mcg daily.

One way to know if supplementation can help you is to do a trial run of vitamin B12 supplementation for at least six to eight weeks. If you are using pills or sublingual lozenges, the most useful form of vitamin B12 is methylcobalamin. Talk to your doctor before starting any new supplement to make sure it is safe for you.

Some people will see improvements after a few days of taking vitamin B12 and may do well taking it in a tablet or lozenge that goes under the tongue. Others will need several months to see results and may need nasal gel or injections for the best improvements. For many people, supplementation has been a very important part of an approach to resolving mental and emotional problems.

Vitamin D

Some studies show that vitamin D deficiency, and often quite severe deficiency, is a common problem in people with HIV. Vitamin D is intimately linked with calcium levels, and deficiency has been linked to a number of health problems, including bone problems, depression, sleep problems, peripheral neuropathy, joint and muscle pain and muscle weakness. It is worth noting that in many of these cases there is a link between vitamin D and the health condition, but it is not certain that a lack of vitamin D causes the health problem.

A blood test can determine whether or not you are deficient in vitamin D. If you are taking vitamin D, the test will show whether you are taking a proper dose for health, while avoiding any risk of taking an amount that could be toxic (although research has shown that toxicity is highly unlikely, even in doses up to 10,000 IU daily when done under medical supervision). The cost of the test may not be covered by all provincial or territorial healthcare plans or may be covered only in certain situations. Check with your doctor for availability in your region.

The best test for vitamin D is the 25-hydroxyvitamin D blood test. There is some debate about the best levels of vitamin D, but most experts believe that the minimum value for health is between 50 and 75 nmol/l. Many people use supplements to boost their levels to more than 100 nmol/l.

While sunlight and fortified foods are two possible sources of vitamin D, the surest way to get adequate levels of this vitamin is by taking a supplement. The best dose to take depends on the person. A daily dose of 1,000 to 2,000 IU is common, but your doctor may recommend a lower or higher dose for you, depending on the level of vitamin D in your blood and any health conditions you might have. People should not take more than 4,000 IU per day without letting their doctor know. Look for the D3 form of the vitamin rather than the D2 form. Vitamin D3 is the active form of the vitamin and there is some evidence that people with HIV have difficulty converting vitamin D2 to vitamin D3. Historically, vitamin D3 supplements are less commonly associated with reports of toxicity than the D2 form.

It is best to do a baseline test so you know your initial level of vitamin D. Then, have regular follow-up tests to see if supplementation has gotten you to an optimal level and that you are not taking too much. Regular testing is the only way to be sure you attain — and then maintain — the optimal level for health.

With proper supplementation, problems caused by vitamin D deficiency can usually be efficiently reversed.

CATIE booklet on side effects

CATIE, the venerable and sharp Canadian AIDS Treatment Information Exchange, has once again provided a terrific manual entitled A Practical Guide to HIV Drug Side Effects (link – http://www.catie.ca/en/practical-guides/hiv-drug-side-effects ).

The booklet, available as a pdf by clicking the link above, covers a wide array of topics. The language is clear and the layout is easy to follow. They provide information on mainstream medical and “alternative” or natural remedies to manage what can be debilitating side effects of HIV therapy.

Topics covered include the range found in the table of contents:

This Guide Is One Tool to Healthy Living
4 Dealing with Side Effects
8 My Health Map
10 Body Weight and Body Shape Changes
14 Diarrhea, Gas and bloating
17 Emotional wellness
21 Fatigue
24 Headaches
27 Menstrual changes
31 Mouth and throat problems
35 Muscle aches and pains
38 Nausea, vomiting and appetite loss
42 Nerve pain and numbness
44 Rash and other problems of the skin,
hair and nails
47 Sexual difficulties
49 Sleep problems
53 Less common side effects: lactic acidosis,
pancreatitis and abacavir hypersensitivity
55 Appendix: Vitamin B12 and Vitamin D
57 More Resources

American Psychiatric Association Task Force on supplements for major depression

The American Psychiatric Association recently commissioned a task force to study the state of “alternative and complementary” therapies for major depression. This follows widespread interest from the scientific community and a considerable accumulation of research to date. The Task Force reported in a 2010 article that focused special attention on these supplements: omega-3 fatty acids (commonly taken as fish oil supplements), St John’s Wort (the botanical Hypericum), Folic acid (a synthetic form of folate, a B vitamin found in leafy green vegetables, citrus fruits, beans, and fortified breads and cereals), and S-adenosyl-L-methionine (SAMe).

We welcome this acknowledgment by the mainstream US medical establishment that supplements have a role to play in treating a disabling condition that affects millions of people per year, and is not always easily treatable. (Only one-third of adult patients newly diagnosed with major depression achieve complete symptom relief when taking one antidepressant, so there is often an extended search for the right combination of drug and other treatment needed for remission.)

Below is a brief recap of some of the latest thinking on these key supplements for depression. Of course NYBC recommends that you use these supplements in consultation with your healthcare provider. More information on these supplements can be found by following the links to the NYBC website.

Omega-3 Fatty Acids (fish oil) recommended as a stand-alone treatment for people concerned about side effects, such as those with multiple medical conditions. It has also been combined with other antidepressants as an adjunct therapy. Fish oil’s blood-thinning property makes it problematic for doses above 3g/day. Added benefit: fish oil supports cardiovascular health.

St. John’s Wort is an herb widely studied and used, especially in Europe, for mild to moderate depression, though it hasn’t proved effective for major depression. Those taking protease inhibitors or certain other drugs should avoid St. John’s Wort because it interferes with their action.

SAMe (S-adenosyl-l-methionine). Supplementing with SAMe increases concentrations of neurotransmitters that influence mood, and multiple studies have confirmed its antidepressant effect. A dose of 400-800mg/day has been studied for mild-to-moderate depression, and 800-1600mg/day for moderate-to-severe. Studied as a stand-alone treatment, or as an adjunct treatment. Added benefit: SAMe supports joint health and liver function.

When combined with an antidepressant, folic acid supplements can improve symptoms, particularly in women. However, folic acid supplements are not a stand-alone treatment for depression. The safe upper limit is 1,000 mcg per day.