Cause of Depression

While great strides have been made in diagnosing and treating depression, millions of Americans still suffer with this difficult-to-treat disease. It is estimated that 15.7 million American adults experienced depression in the past year.1

Antidepressant use is on the rise with one in 10 Americans using them.2,3 Unfortunately, antidepressants only work as little as 50% of the time and come with an array of side effects.4,5

One reason that so many people continue to bear this burden is that most physicians are unaware of the well-documented link between homocysteine and depression.

A simple blood test that measures homocysteine levels, along with a metabolically active form of folate, better known as 5-MTHF, may offer hope to millions of depression sufferers.

Homocysteine and Depression

Homocysteine is an amino acid that, when elevated, can damage the inner linings of the body’s vessels leading to a range of cardiovascular conditions including stroke. There is also a correlation between high homocysteine levels and depression.6,7

Researchers studied this association in a group of 924 middle-aged men. They found that individuals in the upper tertile for homocysteine levels had more than a two-fold increased risk for being depressed compared to those in the lowest tertile.7

Another study found that people with the highest levels of homocysteine (>12 µmol/L) have significantly lower amounts of SAMe, a nutrient required for the synthesis of mood-enhancing neurotransmitters.8 Not surprisingly, they also had lower levels of mood-enhancing neurotransmitters.

The researchers also found that nearly a third of the depressed participants from the study had red blood cell folate levels below normal, and half of these participants had homocysteine levels higher than levels of the two control groups.8

The connection between low folate levels and imbalances in neurotransmitters shouldn’t be surprising since folate is required for the production of neurotransmitters in the brain.

Improvement with 5-MTHF

Once the connection between high homocysteine levels and the occurrence of depressive symptoms was discovered, researchers began to investigate whether the active form of folate, 5-MTHF, could have a beneficial impact on major depression.9,10

The results of these studies open a new door for the treatment of depression. What the scientists discovered was that taking 5-MTHF in addition to antidepressant drugs dramatically improved response rates and did so in a significantly shorter amount of time.

In one study, only 7% of subjects taking an antidepressant drug experienced major improvement on a standard depression score. That number jumped to 19% in those patients taking 5-MTHF in addition to an antidepressant drug.

The results were even more impressive in those with the most severe depression. Improvements of 40% were experienced while taking 5-MTHF in addition to their antidepressant drug, versus just 16% of those only taking the drug by itself.10

In addition to improving symptom severity, 5-MTHF brought about these improvements significantly faster than antidepressant drugs alone. Specifically, the 5-MTHF group saw improvements in just 177 days, compared to 231 days in the control group. For those with the most severe depression, the results were even more dramatic. The median time to improvement took only 85 days, compared to 150 days in the control group. A key finding was that nearly twice as many people in the antidepressant-only group stopped therapy due to adverse events (34%) versus the 5-MTHF group (17.9%), providing evidence of the nutrient’s superior safety profile.10

These results are very encouraging, especially considering the fact that major depression is notoriously difficult to treat, with only about 30% of patients treated with a single antidepressant achieving resolution of their symptoms, a figure that rises to just 50% to 55% when a second drug is added.11,12

This correlation makes supplementing with the metabolically active form of folate, 5-MTHF, a good idea for anyone suffering from depression.


Cognitive Decline, Alzheimer’s Disease, and Aging

Depression by itself is bad enough. But now, scientists are finding that depression can lead to Alzheimer’s disease and cognitive decline.13,14

Research has confirmed the link between elevated homocysteine, cognitive decline, and Alzheimer’s disease.15-17

A study published in the New England Journal of Medicine following elderly participants with dementia found that more than 75% of participants were eventually diagnosed with Alzheimer’s disease over an eight-year follow-up period.18 The researchers reviewed participants’ homocysteine levels and found that for those with homocysteine levels greater than 14 µmol/L, the risk of Alzheimer’s nearly doubled. They concluded that increased plasma levels of homocysteine are a strong, independent risk factor for the development of dementia and Alzheimer’s disease.

Homocysteine alone is not the sole cause of age- related cognitive decline or memory impairment related to Alzheimer’s disease, but there is a significant amount of evidence pointing to its role as a contributing factor.

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