Integrative Medicine for Suicide Prevention:

Effective Models to Prevent a Global Public Health Epidemic

Part 2

by James M. Greenblatt, MD, and Virginia Ross Taylor, PhD

The rate of suicides in the US has increased steadily during the past three decades, as reported by the Centers for Disease Control and Prevention (CDC). To address this disturbing increase, health-care professionals and families need to better understand factors that increase suicide risk. Part 1 in this series addressed several of these factors: genetics, use of antidepressants, and inflammation. Part 2 focuses on nutritional deficiencies – including low levels of cholesterol, Omega-3 fatty acids, vitamin D, and lithium – and uses of social media that can contribute to the risk of suicide. Finally, this article suggests interventions from the field of integrative medicine that we can mobilize to reverse the trend of suicide increases in our nation.

Nutritional Deficiencies

Cholesterol

. An increasing number of studies reveal a high correlation between nutritional deficiencies and increases in depression, anxiety, and suicidal thoughts. Because of its association with neuron signaling, cholesterol has long been recognized as a possible influence on mood disorders. Low cholesterol reduces the ability of serotonin to bind to the serotonin receptors, thereby impairing their function. Serotonin receptors play a major role in the brain and other organs, regulating aggression, anxiety, and impulsiveness (Engleberg).

Several studies have shown that low cholesterol may also contribute to dramatic increases in suicide risk. An early alert that low cholesterol might heighten suicide risk came from a study investigating deaths not related to illness in patients taking statin drugs. Scientists speculated that the statin drugs interfered with the body’s mechanism for stabilizing serotonin and oxytocin receptors (Muldoon, Manuck, Mendelsohn, et al.). Based on this and other evidence of the unintended cognitive effects of these drugs, the FDA issued a warning to consumers and health professionals, urging them to routinely monitor possible psychiatric effects of cholesterol-lowering medications (http://www.fda/gov/ForConsumerUpdates/ucom23330.htm).

More than 20 years ago, researchers uncovered a link between low cholesterol and elevated risk of suicide in patients with mood disorders. In 1995, scientists reported that among psychiatric patients, those whose cholesterol levels were less than or equal to the 25th percentile were twice as likely as others to have made a medically serious suicide attempt (Engleberg; Golier, Marzuk, Leon, et al.).

Although the study received little follow-up at the time, low cholesterol has recently been identified as a risk factor for suicide in several other trials. A trial involving 584 medical records of both suicide attempters and non-suicide attempters evaluated serum cholesterol 24 to 48 hours after patients were admitted to the hospital. The study found that the inpatients who had attempted suicide had significantly lower serum cholesterol than nonsuicidal inpatients (DeBerardis, Marini, Piersanti).

A connection between suicide and low cholesterol has also been studied in young people. In research based on a national survey, investigators examined the relationship between suicide and serum cholesterol in a population of 3237 healthy young adults. A significant association between low HDL cholesterol and the prevalence of lifetime suicide attempts was observed in young men. No association, however, was observed between serum cholesterol and suicidal behavior in young women. The investigators suggested that serum cholesterol was associated with suicidal impulsivity, defined as the rapidity and probability of acting on powerful feelings (Zhang & McKeown).

Other research has also identified a link between cholesterol status and suicide in women. One study analyzed cholesterol levels of 155 female psychiatric inpatients and controls. Levels of cholesterol found in women who had attempted suicide before they were hospitalized were significantly lower than in controls. A further study showed that female patients who had attempted suicide and whose HDL levels remained low were at significantly greater risk of reattempting suicide the following year than female patients who had attempted suicide but whose HDL had been restored to normal levels (Ernet, Yucel, Ozcan, et al.).

Researchers in other countries have also connected low cholesterol levels and suicide risk. A Japanese study found that suicide attempters had significantly lower cholesterol than both patients with other psychiatric problems and normal controls (Kunugi, Takei, Aoki, et al.). A study in Greece measured total cholesterol levels in patients after a suicide attempt and found levels lower than controls not only immediately after the attempt but also later, when the patients had resumed their normal activities (Papadopoulou, Markianos, Christodoulou, et al.). In a Finnish study, 30,000 men were followed for 5 to 8 years. The study investigators found lower serum cholesterol associated with both major depression and death from suicide (Partonen, Haukka, Virtamo, et al.).

Low cholesterol levels appear especially prevalent in those who die by violent suicide. In one study, those who committed suicide by violent means had lower gray-matter cholesterol content compared with o the gray-matter content of nonviolent suicides and controls (Lalovic, Levy , Luheshi, et al.).

Research in the military has also highlighted a link between low serum cholesterol and suicide. In a study of 4462 male US veterans, investigators found that veterans with low serum cholesterol and depression were seven times more likely than veterans with normal cholesterol to die prematurely from suicide and accidents (Boscarino, Erlich, & Hoffman).

A meta-analysis of studies enrolling a total of more than 500,000 patients clearly confirmed a link between low cholesterol and suicidal behavior. Suicide was associated with lower total cholesterol, lower HDL, and lower LDL cholesterol. Compared to patients with the highest level of total cholesterol, the patients with the lowest total cholesterol had a 112% greater risk of suicide and suicidal behaviors (Wu, Ding, Wu, et al.).

The exact mechanism that explains the connection between low cholesterol and suicide is not yet clear. Low cholesterol could lead to alterations in synaptic plasticity in brain regions important in impulse inhibition. Another hypothesis is that lower cholesterol disrupts serotonergic neurotransmission, possibly intensifying depression and suicidal thinking. A possible mediator between both suicidal behavior and low cholesterol is impulsivity. Thus, cholesterol may influence suicide risk through a direct effect on serotonergic activity and traits related to aggression and impulsivity (Favaro, Caregaro, DiPascoli, et al.).

Discovery of a link between cholesterol and suicidal behavior is promising. Low cholesterol levels may be a biological marker that could improve assessment of suicide risk. Detecting this marker might get clinicians closer to identifying potentially suicidal patients before they act.

Vitamin D

. A deficiency in Vitamin D also appears to heighten suicide risk. The influence of vitamin D on brain serotonin levels may explain its role in mood regulation. Vitamin D deficiency may also increase the production of inflammatory cytokines, discussed in Part 1 of this series as a risk factor for suicide.

Given that suicide rates in many countries are highest in the spring, when vitamin D status is lowest, and that low vitamin D status can affect brain function, researchers evaluated whether a low level of 25-hydroxyvitamin D could be a predisposing factor for suicide. After conducting a prospective case-control study among men and women in the military, the investigators concluded that those servicemen and -women with the lowest octile of vitamin D levels had the greatest the risk of suicide. Those in the highest octile of vitamin D levels had the lowest suicide rates. The researchers speculate that additional sunlight exposure and vitamin D supplementation may decrease the risk of suicide among men and women in military service (Umhau, George, Heaney, et al.).

Other research has yielded similar results. One study compared the vitamin D levels of 59 suicide attempters, 17 nonsuicidal depressed patients, and 14 healthy controls, and found that suicide attempters had significantly lower vitamin D levels than either the nonsuicidal depressed patients or the healthy controls (Grudet et al.). A study of young adults suggested that vitamin D predicts depression symptomatology and possibly suicidal thinking (Polak et al.).

Adolescents now tend to spend less time in the sun and consume fewer milk products than the young people of earlier generations, which places them at an increased risk for vitamin D deficiency. They often subsist on diets of fast food, which have been shown to increase depression risk by 36% (Sanchez-Villegasa et al.). Moreover, diets high in omega-6s, which are found in the oils of French fries, chips, and other processed food, crowd out omega-3s in the red blood cells, which can skew the ratio of omega-3s to omega-6s. All of these factors heighten suicide risk for preteens and teenagers.

Omega-3 Essential Fatty Acids

. The essential fatty acids (EFAs) include omega-3s and omega-6s. Both groups are needed by the body, but an imbalance in the two – a higher ratio of omega-6s to omega-3s – may contribute to depression. Omega-3 acids are concentrated in neural tissues and are required for optimal neural functioning. In fact, numerous studies report an association between depressive disorders and low levels of omega-3 fatty acids.

Because of the neurobiological abnormalities they cause, deficiencies in omega-3 fatty acids have been hypothesized to increase suicide risk. Researchers have found that a higher omega-6 to omega-3 ratio predicted suicide attempts among depressed patients (Sublette, Hibbeln, Galfalvy, et al.).

Both cross-national and cross-sectional epidemiological surveys suggest that lower dietary omega-3 fatty acid intake is associated with higher prevalence of suicide-related behaviors. A study in China found the percentage of omega-3s was significantly lower among suicide attempters than among those who did not attempt suicide (Huan, Hamazaki, Sun, et al.).

A connection between omega-3s and suicide has also been studied in the military. One investigation compared the military records of 800 US servicemen and -women who committed suicide between 2002 and 2008 with the records of 800 who had no history of suicide attempts. The servicemen and -women with low blood omega-3 levels were 62% more likely to have committed suicide than those with high levels. Low levels of the omega-3 fatty acid DHA strongly predicted suicide (Lewis, Hibbeln, et al.).

Data from epidemiological studies have also indicated that low consumption of fish, which is rich in omega-3s, may be a risk factor for suicide. In a study of 256,118 Japanese participants that continued for 17 years, those who ate fish every day had a significantly lower risk of death from suicide than those who ate fish less often. Another large epidemiologic study, this time in Northern Finland, examined data from 1,767 participants and found that frequent fish consumption – twice or more each week – significantly reduced depressive symptoms and suicidal thinking (Timonem et al.) .

Longitudinal studies have found that increasing omega-3 fatty acid intake is associated with both reduced risk of depressive symptoms and suicidal ideation. In a randomized controlled intervention trial the treatment group who received omega-3 supplementation experienced a 45% reduction in suicidal thinking (Hallahan, Hibbeln, et al.). Similarly, research in the military also suggests that raising the blood levels of omega-3s and lowering levels of omega-6s decreases the risk of suicidal behavior (Hibbeln & Gow).

Adolescents with eating disorders are even more vulnerable to low levels of omega-3 fatty acids. With periods of prolonged starvation or cycles of binging and purging, they can deprive their bodies of essential vitamins and nutrients and hinder their bodies’ ability to absorb them.

Lithium

. A deficiency in lithium also increases suicide risk. In fact, no overview of risk and protective factors for suicide would be complete without a discussion of lithium, which has consistently been shown to be effective in suicide prevention. While the SSRIs may exacerbate symptoms of agitation, restlessness, irritability or anger that can lead to impulsivity and aggression, lithium may have specific effects against suicide that are independent of mood stabilization. It appears to decrease impulsivity and hostile or aggressive behavior. An association has been demonstrated between reduced suicide risk and long-term lithium treatment in patients with borderline personality disorder (Tondo et al).

One study examined life-threatening or fatal suicidal acts in over 300 bipolar patients before, during, and after long-term lithium treatment. The patients had been ill for more than 8 years. When they were taking lithium, the rate of suicides and suicide attempts decreased nearly 7-fold. When lithium was discontinued, suicidal acts increased 14-fold over the rates found during treatment. The first year the patients were off lithium, the suicide rate rose 20-fold (Tondo et al).

A randomized controlled study of patients with mood disorders and a recent suicide attempt sought to test the role of lithium as a suicide preventative. Contrary to prediction, the survival analysis showed no significant difference in suicidal behaviors between the patients treated with lithium and those treated with placebo. However, later analysis indicated three completed suicides in the placebo group, significantly affecting incidence rates. The researchers concluded that lithium may be effective in lowering the risk of completed suicides in individuals with mood disorders (Lauterbach et al.).

One study examined life-threatening or fatal suicidal acts in more than 300 bipolar patients before, during, and after long-term lithium treatment. The patients had been ill for more than 8 years. When the patients were taking lithium, the rate of suicides and suicide attempts decreased nearly 7-fold. When lithium was discontinued, suicidal acts increased 14-fold over the rates found during treatment. The first year the patients were off lithium, the suicide rate rose 20-fold (Tondo et al.) Epidemiological research reflects these findings, showing a connection between regions with higher lithium prescription rates and reduced suicide risk.

In a recent large systematic review, scientists sought to discover the specific effects of lithium on reducing risks of suicide in patients with unipolar and bipolar mood disorders. They found lithium 60% more effective than placebo in lowering the number of suicides and deaths from any cause in all patients with mood disorders; the benefits were most significant in those with unipolar depression. They speculate that the lithium works not only to prevent relapse of the mood disorder but perhaps also to decrease aggression and impulsivity that often lead to suicide. A better understanding of the mechanism by which lithium reduces suicide risk will lead to a clearer picture of the neurobiology of suicide (Cipriani & Hawton ).

Study of the connection between lithium levels in tap water and the rate of suicide has yielded dramatic results in at least four countries on three continents. Lithium levels in tap water were examined in 27 counties in Texas from 1978 to 1987. They were also studied in 18 municipalities in Japan, and in Austria in a nationwide sample of 6,460 households. All of these studies yielded striking results: the overall suicide rate and the suicide mortality ratio were inversely associated with lithium levels (Schrauzer & Shrestha; Ohgami; Napusta et al.).

More precise understanding of how lithium acts on neurotransmission and cell signaling pathways will lead to better suicide prevention and treatment strategies. While scientists proceed with this research, practitioners should act on the unequivocal knowledge already available by prescribing maintenance lithium for patients with mood disorders who may be at risk of suicide. Lithium is the only drug that has demonstrated such clear benefits. With safe and inexpensive lithium maintenance treatment, the suicide risk for patients with mood disorders – generally estimated at 15% higher than the rate in the general population – is reduced to the suicide rate in the general population.

Social Media

A possible link between social media use and suicide risk deserves study, especially because of the pervasiveness of social media in the lives of most American teenagers and young adults. On a typical day, 70% of teens, or 17 million young people, spend time on social networking sites. In fact, nearly all Americans between 18 and 24 – or 98% of them – use social media (O’Keefe & Clarke Pearson).

Some research studies trace a link between intense involvement with the Internet and disturbances in daily functioning and real-life social interactions (Morahan-Martin & Schumacher). Because of its tendency to promote a virtual life rather than deepening real relationships, the American Pediatrics Association Council on Communications and Media identified “Facebook depression” as a potential problem for both ’tweens and teens (O’Keefe & Clarke-Pearson). One research team described teenagers and young adults as subject to “iDisorders,” which they define as the relationship between technology use and deteriorating psychological health (Rosen et al.).

Heavy Internet use can signal mental health problems, but what about a connection with suicide? It has long been known that media reporting and film and television portrayals of suicide can increase the risk of suicide in young people. On occasion, a rash of suicides using a particular method has occurred after a media depiction of its use. As some methods are more lethal than others, these media events may influence the outcome of suicide attempts modeled after them. Possibly the Internet could promote similar contagion.

Studies from the Pew Research Center suggest that reliance on social media can perpetuate poor body image, problems with self-esteem, and depression. Today 92% of teenagers go online daily, and 24% report being online “almost constantly.” Especially for young girls with eating disorders, this unprecedented connectedness causes serious concerns. Although some online communities promise support in recovery, a larger number, and those increasingly visited by girls struggling with eating disorders, promote just the opposite. Websites such as Pro Ana and Pro Mia draw in young, vulnerable girls with suggestions about how to lose weight quickly and how to deceive parents or doctors who may be monitoring their food intake. Many other sites foster a culture of thinness by featuring photos of girls proudly displaying severe weight loss as ideals and offering inspirational quotes and encouragement to lose even more weight. In the hands of an adolescent struggling with an eating disorder, the Internet is an unmonitored invitation to harmful information with the potential to accelerate the eating disorder.

Nationwide, 68% of girls report having had a negative experience on a social networking site (O’Keefe & Clarke-Pearson). Instances of cybersuicide – cases of attempted or completed suicide influenced by the Internet – have been featured in both the academic and the popular press.

Through social media and the Internet, young people can find both information and communities that encourage suicide. A recent study of suicide sites found them easily accessible through all the major search engines. Although the total numbers of pro-suicide and suicide prevention sites are about the same, the most frequently occurring sites, producing the top three hits, are all prosuicide. The site Alt Suicide Holiday (ASH), for example, is so easily accessible that it can be reached using 10 different web addresses. Prosuicide websites provide explanations of different methods of suicide and compare them by speed, certainty of outcome, and likely amount of pain. While it is illegal in Australia to use the Internet to promote suicide or furnish information about how to do it, in the US these sites are not illegal. Even Wikipedia provides detailed information about suicide methods and their effectiveness rates. The Internet also provides avenues for ordering prescription drugs and poisons that circumvent both customs and government regulation.

Prosuicide websites appear to be accessed by people considering killing themselves. A cross-sectional study based on detailed review of inquest reports of suicides in areas served by 12 coroners in England found that the Internet was consulted before each death. The investigators concluded that easy access to information about suicide methods on suicide websites appears to contribute to a small but significant proportion of suicides, especially information concerning methods (Gannell & Bennewith).

In addition to prosuicide websites, extreme communities have formed online. Some who have visited these sites report having been encouraged to use suicide to end their struggles and find peace. Contributors to chat rooms sometimes exert peer pressure to commit suicide, idolize those who have completed suicide, and encourage others to join with them in suicide pacts. For young people who are ambivalent, this pressure can strengthen their resolve to kill themselves while discouraging them from backing out of a pact or getting help (Biddle et al).

Broader studies link Internet use with suicide. Oxford researchers published findings in 2013 that analyzed 14 previous studies. They found a strong correlation between young people using Internet forums and increased risk of suicide. Vulnerable teens tend to spend more time on the Internet than other teenagers. One study showed that more than half – 59% of young people interviewed – had researched suicide online. Of the teenagers who had harmed themselves, 80% reported researching methods of self-harm online beforehand. Biddle and colleagues (2008) conducted a Web search of 12 terms associated with suicide and found that half of these searches were conducted by those seeking information about method.

What We Can Do

How to untangle the many risk factors that culminate in an act of suicide may remain unclear. But with information now available from the field of integrative medicine, we can lower suicide risk in our patients and in our communities.

These are steps we can take now.

• Implement Nutritional Best Practices.

Nutritional interventions show great promise for suicide prevention. Omega-3 fatty acids and cholesterol are the most important molecules in the synapse, where most brain function occurs. Low levels of Omega-3 fatty acids and low cholesterol levels both interfere with neurotransmission. High levels of Omega-3 acids, on the other hand, even have anti-inflammatory effects. All of these – low Omega-3s, low cholesterol levels, and inflammation – are treatable somatic conditions.

Testing for vitamin D status, Omega-3 levels, lithium, and cholesterol is a simple part of an individualized nutritional assessment. It can reveal deficiencies that are critical to improving psychological wellbeing. If needed, supplementation with vitamin D, Omega-3 fatty acids, cholesterol, and lithium can provide patients with protection against the risk of suicide.

• Test For and Treat Inflammation.

Vulnerable patients should be tested for the presence of pro-inflammatory cytokines and treated with anti-inflammatory medications as needed.

• Identify and Treat Epigenetic Changes that Increase Suicide Risk.

Although a genetic predisposition to suicide is not treatable in the same way, the epigenetic changes associated with suicide can be identified and reversed. Nutritional intervention can modulate epigenetic markers associated with suicide risk.

• Diagnose and Treat Eating Disorders.

A more individualized approach to eating disorder treatment entails identifying and addressing the behavioral, genetic, environmental, and nutritional root causes behind the disorder. Patients need specialized intervention that minimizes frequently co-occurring depression and suicidal behavior.

• Use Social Media to Promote Suicide Prevention.

We need to be realistic about use and accessibility of social media and to educate clients and communities about their dangers. Just as important, we should ensure that suicide prevention is promoted online and on social media platforms. This should include online suicide intervention tools that teens can access.

• Enhance Factors that Protect against Suicide.

This two-part series has focused primarily on factors that increase the risk of suicide. In addition to addressing these factors, health professionals need to promote factors that protect against suicide. These include family and community support and a sense of belonging at school. Religious beliefs and even regular attendance at religious services have recently been identified as protective factors against suicide even beyond their benefits as social support (Burshtein, Dohrenwend, Leva, et al.).

Suicide is a complex problem. On an individual level, it devastates families; on a national level, it is an issue of great public health importance. As suicide involves the interplay of so many factors, it challenges efforts to prevent it. But no problem is more costly in terms of unnecessary suffering and loss of years of potential life. The CDC’s report of the steady increase in suicides in America makes clear that we need more research in neurobiology and epigenetics to gain a better understanding of mechanisms that lead to suicide. As clinicians, we need to do a better job of monitoring patients, especially those with depression, bipolar disorder, eating disorders, and comorbid substance abuse. We need to address nutritional deficiencies and inflammation. Primary care physicians as well need to be vigilant in monitoring patients for whom they have prescribed medications that may heighten risk of suicide-related behaviors. We need more study of factors that protect against suicide. There is no more important task for us as a society than integrating the interventions we know are effective in order to prevent suicide. It is time to bring the results of research into clinical practice to prevent suicide. There is no more urgent need in all of psychiatry.

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