SAM-e, The “Miracle” Supplement for Depression, Arthritis and Liver Health

ProHealth’s Rich Carson calls it, “almost a miracle drug”. I call SAM-e the “triple threat”, for it threatens to vanquish depression, arthritis and liver dysfunction.  SAM-e is a powerful, natural supplement that can be superior to antidepressants and as effective as NSAIDs for osteoarthritis, without the negative side effects. Learn how to use it and where to get it below.


UPDATE 3/12/2021: ProHealth’s ProSAMe is out of stock, so if interested, use Amazon’s Choice, the brand Nature’s Trove SAMe.

In this post, Rich Carson and Karen Lee Richards team up to laud the multiple powers of the natural supplement, SAM-e (S-Adenosyl Methionine).  This is a worthwhile read if you’d like to improve the health of your joints or liver, or could use a healthy mood enhancer.

Rich Carson is my long-time friend, an expert on supplements and the founder of ProHealth, Inc. Karen Lee Richards is Lead Expert specializing in Fibromyalgia and ME/CFS, for HealthCentral’s ChronicPainConnection.

You couldn’t find two better people to tell you about how SAM-e helps promote a natural improvement in the symptoms of osteoarthritis, depression and liver disease.

I call SAM-e the triple threat supplement – relief from joint pain, blue moods and liver ills.  I take 400 milligrams every morning. I’d like to summarize some of Karen Lee Richard’s research on SAM-e from her article, SAM-e: a Hard-Working Molecule that May Help Ease Pain & Brighten Mood. (Thanks to ProHealth for reprint permission.)

Let’s start out by quoting Ms. Richard’s lead paragraph to set the stage:

“Clinical trials have shown SAM-e to be comparable to prescription antidepressants for depression and as effective as NSAIDs for osteoarthritis. But, as SAM-e supports the body’s natural mood and inflammation modulating functions, it doesn’t have all the negative side effects associated with those drugs.”

I’d argue that SAM-e might be superior to prescription antidepressant, cause they’re ineffective for many users with mild to moderate depression, as Dr. Andrew Weil discusses in this post, Dr. Weil’s Four Alternatives to Antidepressant Drugs.

Unlike most supplements, SAM-e (S-adenosyl methionine) is not an herb or a vitamin, but rather a molecule naturally produced in all living cells. It is sold as a dietary supplement in the U.S, although it is powerful enough to be designated as a drug, as it is in at least 14 countries.

Thousands of research studies have been conducted all around the world on SAM-e, investigating its supportive effect in those with many different diseases and conditions, including depression, osteoarthritis, chronic liver disease, fibromyalgia, and Alzheimer’s disease.

Let’s delve a bit into how SAM-e can help with each of these diseases and conditions.


SAM-e and Depression

Significant Improvement Seen in Major Depression with SAM-e

Based on my readings and simple, non-scientific self-experimentation, I’ve argued in Dr. Weil’s Four Alternatives to Antidepressant Drugs and A Little Depressed? 10 Actions That Help Me that antidepressant drugs are NOT the way to go for treating mild to moderate depression. (Get your doctor to weigh in here, cause I’m not one for sure!)

Consider three points that Ms. Richards presents about SAM-e’s value to helping with depression (and then note my comment right after):

•  SAM-e has been studied extensively over three decades as a possible option for those with depression, perhaps because 29% to 46% of patients with major depressive disorder have no response or only a partial response to pharmaceutical antidepressants. At this point, there’s an impressive body of literature suggesting the mood-supporting efficacy of SAM-e.

•  In an open trial, 20 outpatients with major depression were given SAM-e, beginning with 400 mg/day and gradually increasing to 1600 mg/day by day 12.  Nine of the participants had a prior history of not responding to traditional antidepressant treatment. All 20 patients showed significant improvement with SAM-e, including seven of the non-treatment resistant and two of the treatment-resistant patients who experienced a full antidepressant response.

•  A double-blind randomized trial compared the efficacy of supplemental SAM-e with the antidepressant desipramine in 26 patients with major depression. At the end of four weeks, 62% of those given SAM-e had significant improvement compared to 50% of those taking desipramine.

OK, here’s my note about the above three bullet points: The studies cited indicate what they indicate, but, frankly, I’d feel uncomfortable to suggest that people experiencing anything but mild to moderate depression trash their doctor prescribed antidepressants in favor of SAM-e.  If you’ve been diagnosed as having strong/severe depression or other psychiatric issues, DO NOT trash your prescribed drugs in favor of SAM-e; rather, take counsel with your doctor!


SAM-e and Joints

Impressive Results in Osteoarthritis Patients

In her article, Ms. Richards continues with her review of SAM-e, citing how it can benefit those suffering from Osteoarthritis.

She reports that an estimated 27 million people have osteoarthritis, making it the most common form of arthritis.

(Below, I reprint Ms. Richards words; the bold words are my emphasis…)

The pharmaceutical treatment for osteoarthritis is non-steroidal anti-inflammatory drugs (NSAIDs) – either over-the-counter medications like aspirin, ibuprofen and naproxen, or prescription medications like Celebrex, Relafen, Daypro, etc.

While NSAIDs can be effective pain relievers, their regular use can result in some devastating side effects such as ulcers and other gastrointestinal problems, increased blood pressure and kidney damage.

Notwithstanding the side effects, in the long run NSAIDs may actually worsen joint problems because they slow the production of collagen and proteoglycans, which help to make cartilage an effective shock absorber.

By contrast, SAM-e seems to support an anti-inflammatory response equivalent to the effect of NSAIDs, but without the toxic side effects. SAM-e does not harm the digestive tract, nor does it contribute to the breakdown of cartilage. Instead, one study shows it may actually help the body restore damaged cartilage.

•  A meta-analysis of 11 clinical trials involving 1,142 patients was done looking at SAM-e for support of osteoarthritis symptom relief. The study authors concluded, “SAM-e appears to be as effective as NSAIDs in reducing pain and improving functional limitation in patients with OA without the adverse effects often associated with NSAID therapies.”

•  A randomized double-blind cross-over study of 56 patients diagnosed with osteoarthritis of the knee compared SAM-e (1200 mg) with the prescription drug celecoxib (Celebrex 200 mg). The results showed no significant difference between the two – both patient cohorts demonstrated significant improvements in pain and joint function – leading the researchers to conclude that SAM-e was as effective as celecoxib in managing the symptoms of knee osteoarthritis.

•  In a German study, 21 patients with finger osteoarthritis were given SAM-e for three months. MRI scans done on their hands both before and after the treatment period revealed significant structural improvement in the cartilage.


SAM-e and the Liver

It Supports the Prevention and Improvement of Liver Disease

I’m still amazed when I think about how unique is the liver. The liver is unique because it is the only internal human organ capable of regenerating itself. Did you know that a liver reduced to 25% of its normal size could regenerate into a whole liver again?

SAM-e plays a leading role in that regeneration.

SAM-e is thought to be beneficial for those with liver disease by acting as a precursor of antioxidant glutathione; repairing the mitochondrial glutathione transport system; inhibiting the toxic effects of proinflammatory cytokines; and increasing DNA methylation.

There are nearly a thousand published studies documenting SAM-e’s ability to support prevention and improvement in liver disease.  Back to Ms. Richards:

•  In a study of hepatic glutathione levels in patients with liver disease, participants were divided into four groups. Nine patients with alcoholic liver disease were given SAM-e; seven patients with non-alcoholic liver disease were given SAM-e; 8 patients with alcoholic liver disease were given a placebo; and 15 normal subjects served as a control group. Prior to beginning treatment, all patients had very low hepatic glutathione levels compared to controls. Following treatment, patients receiving the SAM-e had a significant increase in their hepatic glutathione levels compared with both the placebo-treated group and controls.

•  When SAM-e was given to 62 patients with alcoholic cirrhosis in a clinical trial, they were significantly less likely to die or require a liver transplant within the next two years, compared with 61 patients who had received a placebo.


SAM-e and Fibromyaliga

SAM-e Is Promising for Fibromyalgia Patients

Although SAM-e has not been studied yet as much for support of fibromyalgia patients as for those with some other illnesses, the results thus far are encouraging. In one double-blind study of 44 patients with primary fibromyalgia, improvements were seen in the areas of clinical disease activity, pain, fatigue, morning stiffness and mood.


SAM-e and Alzheimer’s Disease

It May Help Prevent or Delay Alzheimer’s Disease

Since extremely low levels of SAM-e were found in the cerebrodpinal fluid and brain regions of Alzheimer’s patients in a 1996 study, researchers are examining the potential benefits of supplemental SAM-e in Alzheimer’s.(11)  A recent study stated, “…our findings suggest that dietary supplementation with SAM… holds promise as a therapeutic approach to prevent or delay AD. A preliminary study indicates that SAM can provide some cognitive improvement in AD patients.”


How to Use SAM-e

Facts About SAM-e You Need to Know

Dosage: Recommended therapeutic doses usually range between 400 – 1600 mg a day, although some individuals may require higher doses. Studies suggest that 400 mg per day may be adequate for osteoarthritis patients, while up to 1600 mg a day is often needed for mood support. The usual dose for those with liver disorders has been 1600 mg a day. (As with any addition to your health support regimen, supplementation with SAM-e should be considered only with the approval of your professional healthcare team.)

How to Take SAM-e: SAM-e works best when taken on an empty stomach. Because it is absorbed mainly in the intestine, enteric-coated tablets that allow it to pass through the stomach intact are preferable. Leave tablets in their foil or foil blister packs until you are ready to take them in order to maintain their stability.

Adverse Effects: There seem to be few adverse effects with SAM-e, even at high doses. Occasionally mild gastrointestinal distress has been reported. Since SAM-e can sometimes lead to insomnia, it is usually best to take it early in the morning. Because it plays a role in mood support, SAM-e may trigger manic episodes in people with bipolar disorder.

Contraindications: While there are no confirmed drug interactions with SAM-e, individuals using prescribed medications such as antidepressants, including serotonin re-uptake Inhibitors and MAO inhibitors, should consult a physician before using. Individuals with Parkinson’s disease, bipolar disorder or manic depression should not take SAM-e.


Some Final Words

The Data

The assertions reproduced here are footnoted by Karen Lee Richards’ article her from which they’re extracted.  If you’re interested in the studies she cites, please go to her article, SAM-e: a Hard-Working Molecule that May Help Ease Pain & Brighten Mood.

You’ll discover that more than three decades of solid research support the use of SAM-e to help promote natural improvement in symptoms of osteoarthritis, depression and liver disease.

Where to Buy SAM-e

I suggest you get it at ProHealth, where I get mine.  As mentioned at the outset, try Nature’s Trove SAMe, due to the unavailability of the ProHealth brand.

SAM-e has been one of the cornerstone supplements offered by ProHealth for many years because it’s useful for so many chronic aliments.

ProSAMe This supplement is a wunderkind – it helps to stabilize moods, support healthy joints AND liver function. It’s an important part of my arsenal, but I refrain from taking it all the time, as I like to check in, unadulterated, to see how my natural emotional well being is doing.

Note: Like many things that can be purchased online, ProHealth offers an affiliate program of which I partake. This means if you buy SAM-e from the above link, they will compensate me.  This does not at all affect the price you pay.  If you don’t wish for me to benefit from your purchase, simply go to ProHealth, search for SAM-e and buy it there.

Well, lots to digest with this post.  If you have comments or questions, please submit them in the Comments section below.



Last Updated on February 27, 2022 by Joe Garma

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Joe Garma

I help people live with more vitality and strength. I'm a big believer in sustainability, and am a bit nutty about optimizing my diet, supplements, hormones and exercise. To get exclusive Updates, tips and be on your way to a stronger, more youthful body, join my weekly Newsletter. You can also find me on LinkedIn, Twitter and Instagram.

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